User login
The benefits of first-trimester fetal heart evaluation
The fetal heart typically is examined during the routine 18-20 week obstetric ultrasound screening, and pregnancies with abnormalities on this routine scan are referred for detailed fetal echocardiography. Per multiple practice guidelines, patients deemed to be at high risk of congenital heart defects (CHDs) are referred for fetal echocardiography as well between 18 and 24 weeks’ gestation.
However, with technological advancements in ultrasound, it is possible for obstetricians to detect many major CHDs well before 16 weeks’ gestation. First-trimester fetal heart assessment – and early detection of CHDs – has numerous advantages: It enables early genetic testing, early decision making about continuation or termination of pregnancy, and earlier planning for appropriate management during and after pregnancy. Perioperative outcomes are improved.
At least 75% of CHDs occur in pregnancies with no identifiable maternal, familial, or fetal risk factors. It only seems fitting, therefore, that we check the structure of the fetal heart in all women at the time of their first-trimester screening and sonography at 11-14 weeks. In addition to a determination of fetal viability and gestational age, nuchal translucency measurement, and a check of basic anatomy, .
The value of early detection
Women who have diabetes, congenital defects, in vitro fertilization pregnancies, twin and multiple pregnancies, and certain medication and drug exposures are at high risk for their fetus having a CHD and should undergo fetal echocardiography. Lupus, Sjögren’s, and other medical disorders also are risk factors, as are abnormal biochemical test results.
During the last 10 years, the first-trimester fetal heart evaluation has been performed for all patients who come for a first-trimester screening scan at the University of Maryland’s fetal heart program, part of the Center for Advanced Fetal Care. Approximately 45% of indications for detailed first-trimester fetal heart evaluation have been driven by maternal history, and almost 40% by abnormal basic first-trimester ultrasound findings such as increased nuchal translucency, tricuspid regurgitation, abnormal ductus venosus blood flow, and other structural anomalies.
An estimated 50%-60% of serious cardiac malformations can be detected with a four-chamber heart view during routine first-trimester ultrasound. When the outflow tract relationship and three-vessel views also are examined in the first trimester – as is now recommended in guidelines for second-trimester protocols – an estimated 85%-95% of major CHDs can be detected. One should see the great arteries originating from the left and right sides and crisscrossing each other by a transabdominal scan, or by a transvaginal scan if the transabdominal approach fails to show these features of the fetal heart.
Early sonography not only has been shown to have a high sensitivity but also a specificity of greater than 95% in identifying CHDs. Multiple studies also have demonstrated high negative predictive values in cases with normal findings.1
When defects seen or suspected on routine obstetric ultrasound are then confirmed and diagnosed with detailed fetal echocardiography, women are counseled about outcomes, management options, and mortality – and some patients will choose to terminate their pregnancies.
Psychologically, for the mother, earlier termination is less traumatic. A cross-sectional study of 254 women conducted 2-7 years after pregnancy termination for fetal anomalies found that advanced gestational age at termination was associated with higher levels of grief and posttraumatic stress symptoms, and that long-term psychological morbidity was rare when termination occurred before 14 weeks’ gestation.2 Others studies have shown similar results, with grief and posttraumatic stress time shorter with earlier termination.
First-trimester termination also involves significantly less maternal morbidity and risk, as shown in a retrospective study of 844 patients who underwent a termination of pregnancy after a positive amniocentesis or chorionic villus sampling. Hemorrhages, transfusions, infections, and other complications were significantly higher in second-trimester terminations than in earlier terminations.3
Early fetal heart evaluation can reassure high-risk patients – and low-risk patients as well – when a normal four-chamber heart and great arteries are seen. And when defects are spotted, early evaluation allows appropriate time to test for associated chromosomal abnormalities and genetic syndromes, which in turn improves management. It also gives patients and providers more time to plan and prepare for delivery, surgery, and other specific needs at delivery and after birth.
In our fetal heart program, patients are cared for by a multidisciplinary team of perinatologists with special expertise in the fetal heart, geneticists, cardiologists, cardiac surgeons, and neonatologists. Perioperative outcomes are improved when CHDs are diagnosed prenatally. One meta-analysis showed that prenatal diagnosis reduced the risk of death prior to planned cardiac surgery by about one-fourth relative to patients with a comparable postnatal diagnosis.4
Prenatal diagnosis appears to have generally been improving, although rates remain too low overall. According to the National Institute for Cardiovascular Outcomes Research, which collects data from centers across the United Kingdom and Republic of Ireland, prenatal detection rates of CHDs requiring a procedure in the first year of life moved from about 25% in 2004-2005 to just over 50% between 2010 and 2016.5 More complex lesions, such as hypoplastic left heart syndrome, were more likely to be detected prenatally (80%).
Trends in the United States appear to be similar. A study utilizing the Society of Thoracic Surgeons Congenital Heart Surgery Database found that prenatal detection increased from 26% in 2006 to 42% in 2012.6
A first-trimester evaluation cannot replace the second-trimester echocardiography that currently is performed for high-risk patients, because a small percentage of CHDs – aortic coarctation, valve stenosis, mild tetralogy of Fallot, and hypoplastic left heart, for instance – have the potential to evolve past the first trimester. High-risk patients whose first-trimester evaluations are normal still should undergo another evaluation at 18-20 weeks. The fetal heart completes its embryologic development over the first 8 weeks of gestation, and the majority of CHDs are present at the time of the first-trimester screening (11-14 weeks).
Early evaluation of the fetal heart does not appear to be impacted by obesity. We compared the early evaluation of fetal heart landmarks using two-dimensional sonography with color/power Doppler in obese and nonobese women and found that there were no significant differences in experienced sonographers’ ability to evaluate the four-chamber view, outflow tract relationship, and transverse arches views.
In about 6% of obese women, the evaluation at 11-14 weeks’ gestation required additional imaging with transvaginal sonography. The chances of needing transvaginal ultrasound rose as body mass index rose.1 The median scan time was only 5 minutes longer in the obese group, however, so there is no reason that obesity should be a contraindication to look at the fetal heart.
In fact, it is extremely important that we do early fetal heart evaluations in women who are obese, because the risk of having a fetus with CHD is increasingly being found to be higher in obese women, and because fetal heart assessment with transvaginal ultrasound is an option only in early gestation, when the fetal heart is within the depth of penetration of the vaginal probe. With advancing gestational age, a combined abdominal/transvaginal approach becomes increasingly difficult. Our study also demonstrated a dose-response relationship between maternal obesity and CHD risk.
Preexisting diabetes mellitus, which can occur in conjunction with obesity, has been found to increase the risk for all types of CHDs, especially conotruncal abnormalities. While the pathophysiology is not completely understood, elevated oxidative stress is believed to be the primary trigger.7
First-trimester echocardiography benefits
Patients referred to our fetal heart program for detailed first-trimester fetal heart evaluation – again, a significant number of whom have been found on standard 2-D ultrasound to have increased nuchal translucency thickness or other abnormalities – undergo a four-dimensional fetal echocardiographic technique that utilizes spatiotemporal image correlation and tomographic ultrasound imaging display (STIC-TUI echo) along with color Doppler. The heart is swept from top to bottom in about 10 seconds, and tomographic ultrasound imaging is used offline, after the patient leaves, to develop volume datasets that simultaneously display multiple cross-sectional images.
This method has been implemented into our routine scan at the first trimester as well, and all of our staff have been trained to perform it. Obtaining STIC-TUI by color Doppler allows us to assess all of the important landmarks of the cardiac anatomy in one picture.
In a prospective study of 164 fetuses from 152 patients, we found that first-trimester STIC-TUI echo had 91% sensitivity and 100% specificity for the detection of CHD. Most anomalies were evident in the four-chamber view plane of the TUI display, and the rest were diagnosed in the outflow tract planes. Two cases of CHD missed by this first-trimester evaluation were diagnosed on second-trimester echo and neither involved a major CHD.8
Dr. Turan is associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland, Baltimore.
References
1. J Ultrasound Med. 2019 May;38(5):1269-77.
2. Prenat Diagn. 2005 Mar;25(3):253-60.
3. J Perinat Med. 2018 May 24;46(4):373-8.
4. Ultrasound Obstet Gynecol. 2015 Jun;45(6):631-8.
5. National Congenital Heart Disease Audit Report 2013-2016.
6. Pediatrics. 2015. doi: 10.1542/peds.2014-3783.
7. Echocardiography. 2018 Feb;35(2):244-57.
8. Ultrasound Obstet Gynecol. 2014 Nov;44(5):562-7.
The fetal heart typically is examined during the routine 18-20 week obstetric ultrasound screening, and pregnancies with abnormalities on this routine scan are referred for detailed fetal echocardiography. Per multiple practice guidelines, patients deemed to be at high risk of congenital heart defects (CHDs) are referred for fetal echocardiography as well between 18 and 24 weeks’ gestation.
However, with technological advancements in ultrasound, it is possible for obstetricians to detect many major CHDs well before 16 weeks’ gestation. First-trimester fetal heart assessment – and early detection of CHDs – has numerous advantages: It enables early genetic testing, early decision making about continuation or termination of pregnancy, and earlier planning for appropriate management during and after pregnancy. Perioperative outcomes are improved.
At least 75% of CHDs occur in pregnancies with no identifiable maternal, familial, or fetal risk factors. It only seems fitting, therefore, that we check the structure of the fetal heart in all women at the time of their first-trimester screening and sonography at 11-14 weeks. In addition to a determination of fetal viability and gestational age, nuchal translucency measurement, and a check of basic anatomy, .
The value of early detection
Women who have diabetes, congenital defects, in vitro fertilization pregnancies, twin and multiple pregnancies, and certain medication and drug exposures are at high risk for their fetus having a CHD and should undergo fetal echocardiography. Lupus, Sjögren’s, and other medical disorders also are risk factors, as are abnormal biochemical test results.
During the last 10 years, the first-trimester fetal heart evaluation has been performed for all patients who come for a first-trimester screening scan at the University of Maryland’s fetal heart program, part of the Center for Advanced Fetal Care. Approximately 45% of indications for detailed first-trimester fetal heart evaluation have been driven by maternal history, and almost 40% by abnormal basic first-trimester ultrasound findings such as increased nuchal translucency, tricuspid regurgitation, abnormal ductus venosus blood flow, and other structural anomalies.
An estimated 50%-60% of serious cardiac malformations can be detected with a four-chamber heart view during routine first-trimester ultrasound. When the outflow tract relationship and three-vessel views also are examined in the first trimester – as is now recommended in guidelines for second-trimester protocols – an estimated 85%-95% of major CHDs can be detected. One should see the great arteries originating from the left and right sides and crisscrossing each other by a transabdominal scan, or by a transvaginal scan if the transabdominal approach fails to show these features of the fetal heart.
Early sonography not only has been shown to have a high sensitivity but also a specificity of greater than 95% in identifying CHDs. Multiple studies also have demonstrated high negative predictive values in cases with normal findings.1
When defects seen or suspected on routine obstetric ultrasound are then confirmed and diagnosed with detailed fetal echocardiography, women are counseled about outcomes, management options, and mortality – and some patients will choose to terminate their pregnancies.
Psychologically, for the mother, earlier termination is less traumatic. A cross-sectional study of 254 women conducted 2-7 years after pregnancy termination for fetal anomalies found that advanced gestational age at termination was associated with higher levels of grief and posttraumatic stress symptoms, and that long-term psychological morbidity was rare when termination occurred before 14 weeks’ gestation.2 Others studies have shown similar results, with grief and posttraumatic stress time shorter with earlier termination.
First-trimester termination also involves significantly less maternal morbidity and risk, as shown in a retrospective study of 844 patients who underwent a termination of pregnancy after a positive amniocentesis or chorionic villus sampling. Hemorrhages, transfusions, infections, and other complications were significantly higher in second-trimester terminations than in earlier terminations.3
Early fetal heart evaluation can reassure high-risk patients – and low-risk patients as well – when a normal four-chamber heart and great arteries are seen. And when defects are spotted, early evaluation allows appropriate time to test for associated chromosomal abnormalities and genetic syndromes, which in turn improves management. It also gives patients and providers more time to plan and prepare for delivery, surgery, and other specific needs at delivery and after birth.
In our fetal heart program, patients are cared for by a multidisciplinary team of perinatologists with special expertise in the fetal heart, geneticists, cardiologists, cardiac surgeons, and neonatologists. Perioperative outcomes are improved when CHDs are diagnosed prenatally. One meta-analysis showed that prenatal diagnosis reduced the risk of death prior to planned cardiac surgery by about one-fourth relative to patients with a comparable postnatal diagnosis.4
Prenatal diagnosis appears to have generally been improving, although rates remain too low overall. According to the National Institute for Cardiovascular Outcomes Research, which collects data from centers across the United Kingdom and Republic of Ireland, prenatal detection rates of CHDs requiring a procedure in the first year of life moved from about 25% in 2004-2005 to just over 50% between 2010 and 2016.5 More complex lesions, such as hypoplastic left heart syndrome, were more likely to be detected prenatally (80%).
Trends in the United States appear to be similar. A study utilizing the Society of Thoracic Surgeons Congenital Heart Surgery Database found that prenatal detection increased from 26% in 2006 to 42% in 2012.6
A first-trimester evaluation cannot replace the second-trimester echocardiography that currently is performed for high-risk patients, because a small percentage of CHDs – aortic coarctation, valve stenosis, mild tetralogy of Fallot, and hypoplastic left heart, for instance – have the potential to evolve past the first trimester. High-risk patients whose first-trimester evaluations are normal still should undergo another evaluation at 18-20 weeks. The fetal heart completes its embryologic development over the first 8 weeks of gestation, and the majority of CHDs are present at the time of the first-trimester screening (11-14 weeks).
Early evaluation of the fetal heart does not appear to be impacted by obesity. We compared the early evaluation of fetal heart landmarks using two-dimensional sonography with color/power Doppler in obese and nonobese women and found that there were no significant differences in experienced sonographers’ ability to evaluate the four-chamber view, outflow tract relationship, and transverse arches views.
In about 6% of obese women, the evaluation at 11-14 weeks’ gestation required additional imaging with transvaginal sonography. The chances of needing transvaginal ultrasound rose as body mass index rose.1 The median scan time was only 5 minutes longer in the obese group, however, so there is no reason that obesity should be a contraindication to look at the fetal heart.
In fact, it is extremely important that we do early fetal heart evaluations in women who are obese, because the risk of having a fetus with CHD is increasingly being found to be higher in obese women, and because fetal heart assessment with transvaginal ultrasound is an option only in early gestation, when the fetal heart is within the depth of penetration of the vaginal probe. With advancing gestational age, a combined abdominal/transvaginal approach becomes increasingly difficult. Our study also demonstrated a dose-response relationship between maternal obesity and CHD risk.
Preexisting diabetes mellitus, which can occur in conjunction with obesity, has been found to increase the risk for all types of CHDs, especially conotruncal abnormalities. While the pathophysiology is not completely understood, elevated oxidative stress is believed to be the primary trigger.7
First-trimester echocardiography benefits
Patients referred to our fetal heart program for detailed first-trimester fetal heart evaluation – again, a significant number of whom have been found on standard 2-D ultrasound to have increased nuchal translucency thickness or other abnormalities – undergo a four-dimensional fetal echocardiographic technique that utilizes spatiotemporal image correlation and tomographic ultrasound imaging display (STIC-TUI echo) along with color Doppler. The heart is swept from top to bottom in about 10 seconds, and tomographic ultrasound imaging is used offline, after the patient leaves, to develop volume datasets that simultaneously display multiple cross-sectional images.
This method has been implemented into our routine scan at the first trimester as well, and all of our staff have been trained to perform it. Obtaining STIC-TUI by color Doppler allows us to assess all of the important landmarks of the cardiac anatomy in one picture.
In a prospective study of 164 fetuses from 152 patients, we found that first-trimester STIC-TUI echo had 91% sensitivity and 100% specificity for the detection of CHD. Most anomalies were evident in the four-chamber view plane of the TUI display, and the rest were diagnosed in the outflow tract planes. Two cases of CHD missed by this first-trimester evaluation were diagnosed on second-trimester echo and neither involved a major CHD.8
Dr. Turan is associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland, Baltimore.
References
1. J Ultrasound Med. 2019 May;38(5):1269-77.
2. Prenat Diagn. 2005 Mar;25(3):253-60.
3. J Perinat Med. 2018 May 24;46(4):373-8.
4. Ultrasound Obstet Gynecol. 2015 Jun;45(6):631-8.
5. National Congenital Heart Disease Audit Report 2013-2016.
6. Pediatrics. 2015. doi: 10.1542/peds.2014-3783.
7. Echocardiography. 2018 Feb;35(2):244-57.
8. Ultrasound Obstet Gynecol. 2014 Nov;44(5):562-7.
The fetal heart typically is examined during the routine 18-20 week obstetric ultrasound screening, and pregnancies with abnormalities on this routine scan are referred for detailed fetal echocardiography. Per multiple practice guidelines, patients deemed to be at high risk of congenital heart defects (CHDs) are referred for fetal echocardiography as well between 18 and 24 weeks’ gestation.
However, with technological advancements in ultrasound, it is possible for obstetricians to detect many major CHDs well before 16 weeks’ gestation. First-trimester fetal heart assessment – and early detection of CHDs – has numerous advantages: It enables early genetic testing, early decision making about continuation or termination of pregnancy, and earlier planning for appropriate management during and after pregnancy. Perioperative outcomes are improved.
At least 75% of CHDs occur in pregnancies with no identifiable maternal, familial, or fetal risk factors. It only seems fitting, therefore, that we check the structure of the fetal heart in all women at the time of their first-trimester screening and sonography at 11-14 weeks. In addition to a determination of fetal viability and gestational age, nuchal translucency measurement, and a check of basic anatomy, .
The value of early detection
Women who have diabetes, congenital defects, in vitro fertilization pregnancies, twin and multiple pregnancies, and certain medication and drug exposures are at high risk for their fetus having a CHD and should undergo fetal echocardiography. Lupus, Sjögren’s, and other medical disorders also are risk factors, as are abnormal biochemical test results.
During the last 10 years, the first-trimester fetal heart evaluation has been performed for all patients who come for a first-trimester screening scan at the University of Maryland’s fetal heart program, part of the Center for Advanced Fetal Care. Approximately 45% of indications for detailed first-trimester fetal heart evaluation have been driven by maternal history, and almost 40% by abnormal basic first-trimester ultrasound findings such as increased nuchal translucency, tricuspid regurgitation, abnormal ductus venosus blood flow, and other structural anomalies.
An estimated 50%-60% of serious cardiac malformations can be detected with a four-chamber heart view during routine first-trimester ultrasound. When the outflow tract relationship and three-vessel views also are examined in the first trimester – as is now recommended in guidelines for second-trimester protocols – an estimated 85%-95% of major CHDs can be detected. One should see the great arteries originating from the left and right sides and crisscrossing each other by a transabdominal scan, or by a transvaginal scan if the transabdominal approach fails to show these features of the fetal heart.
Early sonography not only has been shown to have a high sensitivity but also a specificity of greater than 95% in identifying CHDs. Multiple studies also have demonstrated high negative predictive values in cases with normal findings.1
When defects seen or suspected on routine obstetric ultrasound are then confirmed and diagnosed with detailed fetal echocardiography, women are counseled about outcomes, management options, and mortality – and some patients will choose to terminate their pregnancies.
Psychologically, for the mother, earlier termination is less traumatic. A cross-sectional study of 254 women conducted 2-7 years after pregnancy termination for fetal anomalies found that advanced gestational age at termination was associated with higher levels of grief and posttraumatic stress symptoms, and that long-term psychological morbidity was rare when termination occurred before 14 weeks’ gestation.2 Others studies have shown similar results, with grief and posttraumatic stress time shorter with earlier termination.
First-trimester termination also involves significantly less maternal morbidity and risk, as shown in a retrospective study of 844 patients who underwent a termination of pregnancy after a positive amniocentesis or chorionic villus sampling. Hemorrhages, transfusions, infections, and other complications were significantly higher in second-trimester terminations than in earlier terminations.3
Early fetal heart evaluation can reassure high-risk patients – and low-risk patients as well – when a normal four-chamber heart and great arteries are seen. And when defects are spotted, early evaluation allows appropriate time to test for associated chromosomal abnormalities and genetic syndromes, which in turn improves management. It also gives patients and providers more time to plan and prepare for delivery, surgery, and other specific needs at delivery and after birth.
In our fetal heart program, patients are cared for by a multidisciplinary team of perinatologists with special expertise in the fetal heart, geneticists, cardiologists, cardiac surgeons, and neonatologists. Perioperative outcomes are improved when CHDs are diagnosed prenatally. One meta-analysis showed that prenatal diagnosis reduced the risk of death prior to planned cardiac surgery by about one-fourth relative to patients with a comparable postnatal diagnosis.4
Prenatal diagnosis appears to have generally been improving, although rates remain too low overall. According to the National Institute for Cardiovascular Outcomes Research, which collects data from centers across the United Kingdom and Republic of Ireland, prenatal detection rates of CHDs requiring a procedure in the first year of life moved from about 25% in 2004-2005 to just over 50% between 2010 and 2016.5 More complex lesions, such as hypoplastic left heart syndrome, were more likely to be detected prenatally (80%).
Trends in the United States appear to be similar. A study utilizing the Society of Thoracic Surgeons Congenital Heart Surgery Database found that prenatal detection increased from 26% in 2006 to 42% in 2012.6
A first-trimester evaluation cannot replace the second-trimester echocardiography that currently is performed for high-risk patients, because a small percentage of CHDs – aortic coarctation, valve stenosis, mild tetralogy of Fallot, and hypoplastic left heart, for instance – have the potential to evolve past the first trimester. High-risk patients whose first-trimester evaluations are normal still should undergo another evaluation at 18-20 weeks. The fetal heart completes its embryologic development over the first 8 weeks of gestation, and the majority of CHDs are present at the time of the first-trimester screening (11-14 weeks).
Early evaluation of the fetal heart does not appear to be impacted by obesity. We compared the early evaluation of fetal heart landmarks using two-dimensional sonography with color/power Doppler in obese and nonobese women and found that there were no significant differences in experienced sonographers’ ability to evaluate the four-chamber view, outflow tract relationship, and transverse arches views.
In about 6% of obese women, the evaluation at 11-14 weeks’ gestation required additional imaging with transvaginal sonography. The chances of needing transvaginal ultrasound rose as body mass index rose.1 The median scan time was only 5 minutes longer in the obese group, however, so there is no reason that obesity should be a contraindication to look at the fetal heart.
In fact, it is extremely important that we do early fetal heart evaluations in women who are obese, because the risk of having a fetus with CHD is increasingly being found to be higher in obese women, and because fetal heart assessment with transvaginal ultrasound is an option only in early gestation, when the fetal heart is within the depth of penetration of the vaginal probe. With advancing gestational age, a combined abdominal/transvaginal approach becomes increasingly difficult. Our study also demonstrated a dose-response relationship between maternal obesity and CHD risk.
Preexisting diabetes mellitus, which can occur in conjunction with obesity, has been found to increase the risk for all types of CHDs, especially conotruncal abnormalities. While the pathophysiology is not completely understood, elevated oxidative stress is believed to be the primary trigger.7
First-trimester echocardiography benefits
Patients referred to our fetal heart program for detailed first-trimester fetal heart evaluation – again, a significant number of whom have been found on standard 2-D ultrasound to have increased nuchal translucency thickness or other abnormalities – undergo a four-dimensional fetal echocardiographic technique that utilizes spatiotemporal image correlation and tomographic ultrasound imaging display (STIC-TUI echo) along with color Doppler. The heart is swept from top to bottom in about 10 seconds, and tomographic ultrasound imaging is used offline, after the patient leaves, to develop volume datasets that simultaneously display multiple cross-sectional images.
This method has been implemented into our routine scan at the first trimester as well, and all of our staff have been trained to perform it. Obtaining STIC-TUI by color Doppler allows us to assess all of the important landmarks of the cardiac anatomy in one picture.
In a prospective study of 164 fetuses from 152 patients, we found that first-trimester STIC-TUI echo had 91% sensitivity and 100% specificity for the detection of CHD. Most anomalies were evident in the four-chamber view plane of the TUI display, and the rest were diagnosed in the outflow tract planes. Two cases of CHD missed by this first-trimester evaluation were diagnosed on second-trimester echo and neither involved a major CHD.8
Dr. Turan is associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland, Baltimore.
References
1. J Ultrasound Med. 2019 May;38(5):1269-77.
2. Prenat Diagn. 2005 Mar;25(3):253-60.
3. J Perinat Med. 2018 May 24;46(4):373-8.
4. Ultrasound Obstet Gynecol. 2015 Jun;45(6):631-8.
5. National Congenital Heart Disease Audit Report 2013-2016.
6. Pediatrics. 2015. doi: 10.1542/peds.2014-3783.
7. Echocardiography. 2018 Feb;35(2):244-57.
8. Ultrasound Obstet Gynecol. 2014 Nov;44(5):562-7.
Considering congenital heart defects early
Regardless of political or ideological views, detecting the embryonic heartbeat in the first trimester is a major milestone for a patient. Measured via ultrasound, normal beating of 90-110 bpm around 6 weeks’ gestation indicates a high probability of a successful pregnancy. Once the embryo becomes a fetus, around gestational weeks 8-9, a strong fetal heartbeat of 140-170 bpm should be detected. Finding a heartbeat is a reassuring sign. However, simply seeing and/or hearing the heart is not enough to ensure that the fetus will develop without problems.
Congenital heart defects (CHDs) are the most common birth defects worldwide and, although many CHDs can be mild forms, approximately 25% are severe forms requiring early detection and intervention.1 In addition, CHDs in the fetus can cause miscarriage, stillbirth, and infant deaths.
A 2014 analysis of data from the Wisconsin Stillbirth Service Program revealed that 2 An analysis of the Active Malformations Surveillance Program at Brigham and Women’s Hospital also revealed CHDs as a major cause of stillbirths.3 In addition, a retrospective study of the Metropolitan Atlanta Congenital Defects program showed that, although 1-year survival of infants with severe CHDs has improved over the last 4 decades, mortality remains high.1
Because advances in medicine and surgical procedures have significantly reduced deaths attributable to CHDs, more women with a preexisting heart condition are becoming pregnant. Women who have a CHD, even if corrected, can experience pregnancy complications such as arrhythmias, thrombosis, and cardiac dysfunction. In addition, babies of women with CHDs have a higher risk of developing cardiac defects as well.
Therefore, it is critical that we closely monitor our patients – both the mother and her baby – to ensure that the fetal heart is present, functional, and developing normally. We have invited Dr. Shifa Turan, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland and director of the Fetal Heart Program at the University of Maryland Medical Center, both in Baltimore, to discuss the fetal heart. In this first section of a two-part series, Dr. Turan addresses how we can and should monitor fetal heart development.
Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
References
1. Pediatrics. 2013 May. doi: 10.1542/peds.2012-3435).
2. Am J Med Genet A. 2014 Mar. doi: 10.1002/ajmg.a.36366.
3. Birth Defects Res. 2018 Jan. 29. doi: 10.1002/bdr2.1097.
Regardless of political or ideological views, detecting the embryonic heartbeat in the first trimester is a major milestone for a patient. Measured via ultrasound, normal beating of 90-110 bpm around 6 weeks’ gestation indicates a high probability of a successful pregnancy. Once the embryo becomes a fetus, around gestational weeks 8-9, a strong fetal heartbeat of 140-170 bpm should be detected. Finding a heartbeat is a reassuring sign. However, simply seeing and/or hearing the heart is not enough to ensure that the fetus will develop without problems.
Congenital heart defects (CHDs) are the most common birth defects worldwide and, although many CHDs can be mild forms, approximately 25% are severe forms requiring early detection and intervention.1 In addition, CHDs in the fetus can cause miscarriage, stillbirth, and infant deaths.
A 2014 analysis of data from the Wisconsin Stillbirth Service Program revealed that 2 An analysis of the Active Malformations Surveillance Program at Brigham and Women’s Hospital also revealed CHDs as a major cause of stillbirths.3 In addition, a retrospective study of the Metropolitan Atlanta Congenital Defects program showed that, although 1-year survival of infants with severe CHDs has improved over the last 4 decades, mortality remains high.1
Because advances in medicine and surgical procedures have significantly reduced deaths attributable to CHDs, more women with a preexisting heart condition are becoming pregnant. Women who have a CHD, even if corrected, can experience pregnancy complications such as arrhythmias, thrombosis, and cardiac dysfunction. In addition, babies of women with CHDs have a higher risk of developing cardiac defects as well.
Therefore, it is critical that we closely monitor our patients – both the mother and her baby – to ensure that the fetal heart is present, functional, and developing normally. We have invited Dr. Shifa Turan, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland and director of the Fetal Heart Program at the University of Maryland Medical Center, both in Baltimore, to discuss the fetal heart. In this first section of a two-part series, Dr. Turan addresses how we can and should monitor fetal heart development.
Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
References
1. Pediatrics. 2013 May. doi: 10.1542/peds.2012-3435).
2. Am J Med Genet A. 2014 Mar. doi: 10.1002/ajmg.a.36366.
3. Birth Defects Res. 2018 Jan. 29. doi: 10.1002/bdr2.1097.
Regardless of political or ideological views, detecting the embryonic heartbeat in the first trimester is a major milestone for a patient. Measured via ultrasound, normal beating of 90-110 bpm around 6 weeks’ gestation indicates a high probability of a successful pregnancy. Once the embryo becomes a fetus, around gestational weeks 8-9, a strong fetal heartbeat of 140-170 bpm should be detected. Finding a heartbeat is a reassuring sign. However, simply seeing and/or hearing the heart is not enough to ensure that the fetus will develop without problems.
Congenital heart defects (CHDs) are the most common birth defects worldwide and, although many CHDs can be mild forms, approximately 25% are severe forms requiring early detection and intervention.1 In addition, CHDs in the fetus can cause miscarriage, stillbirth, and infant deaths.
A 2014 analysis of data from the Wisconsin Stillbirth Service Program revealed that 2 An analysis of the Active Malformations Surveillance Program at Brigham and Women’s Hospital also revealed CHDs as a major cause of stillbirths.3 In addition, a retrospective study of the Metropolitan Atlanta Congenital Defects program showed that, although 1-year survival of infants with severe CHDs has improved over the last 4 decades, mortality remains high.1
Because advances in medicine and surgical procedures have significantly reduced deaths attributable to CHDs, more women with a preexisting heart condition are becoming pregnant. Women who have a CHD, even if corrected, can experience pregnancy complications such as arrhythmias, thrombosis, and cardiac dysfunction. In addition, babies of women with CHDs have a higher risk of developing cardiac defects as well.
Therefore, it is critical that we closely monitor our patients – both the mother and her baby – to ensure that the fetal heart is present, functional, and developing normally. We have invited Dr. Shifa Turan, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland and director of the Fetal Heart Program at the University of Maryland Medical Center, both in Baltimore, to discuss the fetal heart. In this first section of a two-part series, Dr. Turan addresses how we can and should monitor fetal heart development.
Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
References
1. Pediatrics. 2013 May. doi: 10.1542/peds.2012-3435).
2. Am J Med Genet A. 2014 Mar. doi: 10.1002/ajmg.a.36366.
3. Birth Defects Res. 2018 Jan. 29. doi: 10.1002/bdr2.1097.
Younger men and women show similar rates of osteopenia
according to findings from a cross-sectional study.
The high prevalence of osteopenia – once viewed as restricted largely to older women – in the study’s younger, cross-sex population should spur physicians to ask all patients about calcium intake and exercise as well as to screen for osteoporosis in all patients, Martha A. Bass, PhD,`wrote in the Journal of the American Osteopathic Association.
“It is important that early detection of the precursors for osteoporosis become part of the annual physical for people in this age range, as well as in older patients,” noted Dr Bass of the University of Mississippi School of Applied Sciences in Oxford, and coauthors. “Primary care physicians should begin educating patients as early as adolescence or young adulthood so the consequences of osteoporosis can be prevented. The result would be the prevention of future bone fractures and the morbidity and mortality associated with bone fractures, thus leading to improved quality of life.”
The researchers set out to examine the likelihood of low bone mineral density (BMD) and related risk factors in 173 adults aged 35-50 years. All of the participants completed a questionnaire assessing calcium intake, weekly exercise, smoking, and body mass index, and all underwent screening for BMD. The study’s primary outcome was BMD at the femoral neck, trochanter, intertrochanteric crest, total femur, and lumbar spine.
Among the 81 men in the sample, 25 (30%) had a normal body mass index, and the remainder were either overweight (47.5%) or obese (22.5%). One of the women was underweight, 48.9% were normal weight, 28.3% were overweight, and 21.7% were obese.
Most of the sample, regardless of gender, reported consuming fewer than three dairy items per day. Exercise frequency was better, with 68% of men and 56.4% of women saying they exercised at least 20 times per month.
There were no total femur osteoporosis findings in either sex. However, osteopenia at the femoral neck was present in 28.4% of the men and 26.1% of the women. Osteopenia at the lumbar spine occurred in 21% of men and 15.2% of women, with 6.2% of men and 2.2% of women showing osteoporosis at this site.
An adjusted analysis determined that exercise correlated significantly and negatively with femoral neck BMD in men. But in women, there was a significant and positive correlation with BMD at the lumbar spine and at all femoral measurements.
Body mass index also played into the risk picture. Among men, almost all BMD measurements (trochanter, intertrochanteric crest, total femur, and lumbar spine) were positively associated with higher BMI. For women, higher BMI was associated with better BMD at the all the femoral sites, but not at the lumbar spine.
The negative correlation between femoral neck BMD and exercise in men seemed to contradict findings from previous studies. The authors said that could be a result of reporting bias, with men overestimating their amount of exercise, and could suggest that higher BMI confers some protection against bone loss in men.
The study found no significant correlations between dairy intake and BMD at any site in either sex. The finding suggests that both sexes need to improve both vitamin D and calcium intake.
None of the authors reported any financial disclosures.
SOURCE: Bass MA et al. J Am Osteopath Assoc. 2019;119(6):357-63.
according to findings from a cross-sectional study.
The high prevalence of osteopenia – once viewed as restricted largely to older women – in the study’s younger, cross-sex population should spur physicians to ask all patients about calcium intake and exercise as well as to screen for osteoporosis in all patients, Martha A. Bass, PhD,`wrote in the Journal of the American Osteopathic Association.
“It is important that early detection of the precursors for osteoporosis become part of the annual physical for people in this age range, as well as in older patients,” noted Dr Bass of the University of Mississippi School of Applied Sciences in Oxford, and coauthors. “Primary care physicians should begin educating patients as early as adolescence or young adulthood so the consequences of osteoporosis can be prevented. The result would be the prevention of future bone fractures and the morbidity and mortality associated with bone fractures, thus leading to improved quality of life.”
The researchers set out to examine the likelihood of low bone mineral density (BMD) and related risk factors in 173 adults aged 35-50 years. All of the participants completed a questionnaire assessing calcium intake, weekly exercise, smoking, and body mass index, and all underwent screening for BMD. The study’s primary outcome was BMD at the femoral neck, trochanter, intertrochanteric crest, total femur, and lumbar spine.
Among the 81 men in the sample, 25 (30%) had a normal body mass index, and the remainder were either overweight (47.5%) or obese (22.5%). One of the women was underweight, 48.9% were normal weight, 28.3% were overweight, and 21.7% were obese.
Most of the sample, regardless of gender, reported consuming fewer than three dairy items per day. Exercise frequency was better, with 68% of men and 56.4% of women saying they exercised at least 20 times per month.
There were no total femur osteoporosis findings in either sex. However, osteopenia at the femoral neck was present in 28.4% of the men and 26.1% of the women. Osteopenia at the lumbar spine occurred in 21% of men and 15.2% of women, with 6.2% of men and 2.2% of women showing osteoporosis at this site.
An adjusted analysis determined that exercise correlated significantly and negatively with femoral neck BMD in men. But in women, there was a significant and positive correlation with BMD at the lumbar spine and at all femoral measurements.
Body mass index also played into the risk picture. Among men, almost all BMD measurements (trochanter, intertrochanteric crest, total femur, and lumbar spine) were positively associated with higher BMI. For women, higher BMI was associated with better BMD at the all the femoral sites, but not at the lumbar spine.
The negative correlation between femoral neck BMD and exercise in men seemed to contradict findings from previous studies. The authors said that could be a result of reporting bias, with men overestimating their amount of exercise, and could suggest that higher BMI confers some protection against bone loss in men.
The study found no significant correlations between dairy intake and BMD at any site in either sex. The finding suggests that both sexes need to improve both vitamin D and calcium intake.
None of the authors reported any financial disclosures.
SOURCE: Bass MA et al. J Am Osteopath Assoc. 2019;119(6):357-63.
according to findings from a cross-sectional study.
The high prevalence of osteopenia – once viewed as restricted largely to older women – in the study’s younger, cross-sex population should spur physicians to ask all patients about calcium intake and exercise as well as to screen for osteoporosis in all patients, Martha A. Bass, PhD,`wrote in the Journal of the American Osteopathic Association.
“It is important that early detection of the precursors for osteoporosis become part of the annual physical for people in this age range, as well as in older patients,” noted Dr Bass of the University of Mississippi School of Applied Sciences in Oxford, and coauthors. “Primary care physicians should begin educating patients as early as adolescence or young adulthood so the consequences of osteoporosis can be prevented. The result would be the prevention of future bone fractures and the morbidity and mortality associated with bone fractures, thus leading to improved quality of life.”
The researchers set out to examine the likelihood of low bone mineral density (BMD) and related risk factors in 173 adults aged 35-50 years. All of the participants completed a questionnaire assessing calcium intake, weekly exercise, smoking, and body mass index, and all underwent screening for BMD. The study’s primary outcome was BMD at the femoral neck, trochanter, intertrochanteric crest, total femur, and lumbar spine.
Among the 81 men in the sample, 25 (30%) had a normal body mass index, and the remainder were either overweight (47.5%) or obese (22.5%). One of the women was underweight, 48.9% were normal weight, 28.3% were overweight, and 21.7% were obese.
Most of the sample, regardless of gender, reported consuming fewer than three dairy items per day. Exercise frequency was better, with 68% of men and 56.4% of women saying they exercised at least 20 times per month.
There were no total femur osteoporosis findings in either sex. However, osteopenia at the femoral neck was present in 28.4% of the men and 26.1% of the women. Osteopenia at the lumbar spine occurred in 21% of men and 15.2% of women, with 6.2% of men and 2.2% of women showing osteoporosis at this site.
An adjusted analysis determined that exercise correlated significantly and negatively with femoral neck BMD in men. But in women, there was a significant and positive correlation with BMD at the lumbar spine and at all femoral measurements.
Body mass index also played into the risk picture. Among men, almost all BMD measurements (trochanter, intertrochanteric crest, total femur, and lumbar spine) were positively associated with higher BMI. For women, higher BMI was associated with better BMD at the all the femoral sites, but not at the lumbar spine.
The negative correlation between femoral neck BMD and exercise in men seemed to contradict findings from previous studies. The authors said that could be a result of reporting bias, with men overestimating their amount of exercise, and could suggest that higher BMI confers some protection against bone loss in men.
The study found no significant correlations between dairy intake and BMD at any site in either sex. The finding suggests that both sexes need to improve both vitamin D and calcium intake.
None of the authors reported any financial disclosures.
SOURCE: Bass MA et al. J Am Osteopath Assoc. 2019;119(6):357-63.
FROM THE JOURNAL OF THE AMERICAN OSTEOPATHIC ASSOCIATION
FDA: Vinpocetine associated with fetal harms, miscarriage
according to a statement from the agency.
This warning is based on data reviewed by the FDA, including a report from the National Institutes of Health’s National Toxicology Program, that show associations between vinpocetine use and decreased fetal weight and increased risk of miscarriage in animals. The agency is particularly concerned because products containing this ingredient, including those marketed as improving energy and memory, are widely available to women of childbearing age. As a result, the agency has recommended these women not take vinpocetine.
Vinpocetine is a synthetically produced compound used in dietary supplements either on its own or in combination and may be referred to as Vinca minor extract, lesser periwinkle extract, or common periwinkle extract on product labels. Although vinpocetine is regulated in some countries as a prescription drug, when it’s sold in dietary supplements in the United States, the FDA does not usually review those products or their labeling before they become available to consumers under the same safety and effectiveness standards used to evaluate drug products.
“Today’s safety warning is just one of many steps the FDA is taking to adapt to the realities of the evolving dietary supplement industry,” according to the agency’s statement. “Protecting the public from unsafe dietary supplements remains a top priority for the FDA.”
The full statement regarding vinpocetine and its risks can be found on the FDA website.
according to a statement from the agency.
This warning is based on data reviewed by the FDA, including a report from the National Institutes of Health’s National Toxicology Program, that show associations between vinpocetine use and decreased fetal weight and increased risk of miscarriage in animals. The agency is particularly concerned because products containing this ingredient, including those marketed as improving energy and memory, are widely available to women of childbearing age. As a result, the agency has recommended these women not take vinpocetine.
Vinpocetine is a synthetically produced compound used in dietary supplements either on its own or in combination and may be referred to as Vinca minor extract, lesser periwinkle extract, or common periwinkle extract on product labels. Although vinpocetine is regulated in some countries as a prescription drug, when it’s sold in dietary supplements in the United States, the FDA does not usually review those products or their labeling before they become available to consumers under the same safety and effectiveness standards used to evaluate drug products.
“Today’s safety warning is just one of many steps the FDA is taking to adapt to the realities of the evolving dietary supplement industry,” according to the agency’s statement. “Protecting the public from unsafe dietary supplements remains a top priority for the FDA.”
The full statement regarding vinpocetine and its risks can be found on the FDA website.
according to a statement from the agency.
This warning is based on data reviewed by the FDA, including a report from the National Institutes of Health’s National Toxicology Program, that show associations between vinpocetine use and decreased fetal weight and increased risk of miscarriage in animals. The agency is particularly concerned because products containing this ingredient, including those marketed as improving energy and memory, are widely available to women of childbearing age. As a result, the agency has recommended these women not take vinpocetine.
Vinpocetine is a synthetically produced compound used in dietary supplements either on its own or in combination and may be referred to as Vinca minor extract, lesser periwinkle extract, or common periwinkle extract on product labels. Although vinpocetine is regulated in some countries as a prescription drug, when it’s sold in dietary supplements in the United States, the FDA does not usually review those products or their labeling before they become available to consumers under the same safety and effectiveness standards used to evaluate drug products.
“Today’s safety warning is just one of many steps the FDA is taking to adapt to the realities of the evolving dietary supplement industry,” according to the agency’s statement. “Protecting the public from unsafe dietary supplements remains a top priority for the FDA.”
The full statement regarding vinpocetine and its risks can be found on the FDA website.
Breastfeeding protects against intussusception
LJUBLJANA, SLOVENIA – in a German case-control study.
Two other potent risk factors for intussusception in children less than 1 year old were identified: a family history of intussusception, and an episode of gastroenteritis, Doris F. Oberle, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Dr. Oberle, of the Paul Ehrlich Institute in Langen, Germany, presented a retrospective study of 116 meticulously validated cases of intussusception in infancy treated at 19 German pediatric centers during 2010-2014 and 272 controls matched by birth month, sex, and location. A standardized interview was conducted with the parents of all study participants.
Rotavirus vaccine was added to the German national vaccination schedule in 2013. In a multivariate logistic regression analysis, the risk of intussusception was increased by 5.4-fold following the first dose of the vaccine, compared with nonrecipients. However, subsequent doses of rotavirus vaccine were not associated with any excess risk.
In addition, a family history of intussusception was linked to a 4.2-fold increased risk, while an episode of gastroenteritis during the first year of life was associated with a 4.7-fold elevated risk.
In a novel finding, breastfeeding was independently associated with a 44% reduction in the risk of intussusception, compared with that of bottle-fed babies.
The most common presenting signs and symptoms of intussusception were vomiting, abdominal pain, hematochezia, pallor, and reduced appetite, each present in at least half of affected infants.
Dr. Oberle reported having no financial conflicts regarding her study, supported by the Paul Ehrlich Institute.
LJUBLJANA, SLOVENIA – in a German case-control study.
Two other potent risk factors for intussusception in children less than 1 year old were identified: a family history of intussusception, and an episode of gastroenteritis, Doris F. Oberle, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Dr. Oberle, of the Paul Ehrlich Institute in Langen, Germany, presented a retrospective study of 116 meticulously validated cases of intussusception in infancy treated at 19 German pediatric centers during 2010-2014 and 272 controls matched by birth month, sex, and location. A standardized interview was conducted with the parents of all study participants.
Rotavirus vaccine was added to the German national vaccination schedule in 2013. In a multivariate logistic regression analysis, the risk of intussusception was increased by 5.4-fold following the first dose of the vaccine, compared with nonrecipients. However, subsequent doses of rotavirus vaccine were not associated with any excess risk.
In addition, a family history of intussusception was linked to a 4.2-fold increased risk, while an episode of gastroenteritis during the first year of life was associated with a 4.7-fold elevated risk.
In a novel finding, breastfeeding was independently associated with a 44% reduction in the risk of intussusception, compared with that of bottle-fed babies.
The most common presenting signs and symptoms of intussusception were vomiting, abdominal pain, hematochezia, pallor, and reduced appetite, each present in at least half of affected infants.
Dr. Oberle reported having no financial conflicts regarding her study, supported by the Paul Ehrlich Institute.
LJUBLJANA, SLOVENIA – in a German case-control study.
Two other potent risk factors for intussusception in children less than 1 year old were identified: a family history of intussusception, and an episode of gastroenteritis, Doris F. Oberle, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Dr. Oberle, of the Paul Ehrlich Institute in Langen, Germany, presented a retrospective study of 116 meticulously validated cases of intussusception in infancy treated at 19 German pediatric centers during 2010-2014 and 272 controls matched by birth month, sex, and location. A standardized interview was conducted with the parents of all study participants.
Rotavirus vaccine was added to the German national vaccination schedule in 2013. In a multivariate logistic regression analysis, the risk of intussusception was increased by 5.4-fold following the first dose of the vaccine, compared with nonrecipients. However, subsequent doses of rotavirus vaccine were not associated with any excess risk.
In addition, a family history of intussusception was linked to a 4.2-fold increased risk, while an episode of gastroenteritis during the first year of life was associated with a 4.7-fold elevated risk.
In a novel finding, breastfeeding was independently associated with a 44% reduction in the risk of intussusception, compared with that of bottle-fed babies.
The most common presenting signs and symptoms of intussusception were vomiting, abdominal pain, hematochezia, pallor, and reduced appetite, each present in at least half of affected infants.
Dr. Oberle reported having no financial conflicts regarding her study, supported by the Paul Ehrlich Institute.
REPORTING FROM ESPID 2019
Systematic review indicates cutaneous laser therapy may be safe during pregnancy
according to the results of a systematic review of 22 studies.
Among 380 women in all trimesters of pregnancy who were treated with various laser wavelengths, the only clinically significant event was a case of premature rupture of membranes (PROM) “without further morbidity,” wrote Eric C. Wilkerson, MD, of Skin Laser & Surgery Specialists of NY and NJ in New York, and associates. In that case, the cause was not clear, there was no further morbidity, “and it was uncertain whether this was related to the laser procedure.”
However, only 22 studies were identified between 1960 and 2017, all of which were case reports or series, published from 1994 to 2015. “[Thus far,] the best evidence exists for the safety of the carbon dioxide laser, particularly in the treatment of condyloma,” they wrote in Dermatologic Surgery.
Elective laser treatments are usually not recommended during pregnancy, but no evidence supports this, Dr. Wilkerson and coauthors wrote. Therefore, they searched for studies indexed in PubMed, Google Scholar, the Cochrane Library, or the EBSCO CINAHL Plus Database from 1960 to 2017. They also searched LexisNexis for relevant legal cases, but found none.
The women in the 22 case reports and series were aged 14-41 years and received laser therapy for cervical adenocarcinoma, urolithiasis, condyloma acuminata, cervical carcinoma in situ, cutaneous scarring, Buschke-Löwenstein tumor, verrucous carcinoma, and acne vulgaris. Modalities included 504-nm pulsed-dye laser, 532-nm potassium titanyl phosphate, 1,064-nm neodymium:YAG, 2,100-nm holmium:YAG, and 10,600-nm CO2.
Apart from the case of PROM, there were no instances of fetal morbidity or mortality, premature labor or preterm birth, or detectable fetal stress, the authors wrote. The case of PROM occurred at 35 weeks, 4 days after the mother had received CO2 laser therapy for condyloma acuminata. She delivered normally approximately 1 week later. There also were several cases of premature contractions without true labor, all of which responded to tocolytic therapy. (In the same study, there also were two cases of PROM in women 7 and 10 weeks after the same procedure, but were thought to be unrelated.)
The thickness of the pregnant abdomen, uterus, and amniotic fluid makes it “very unlikely” that clinically significant amounts of laser energy would reach the fetus during cutaneous laser therapy, the authors noted. Certain topical anesthetics, such as lidocaine and prilocaine, also appear safe during pregnancy “and may potentially decrease concern for fetal stress secondary to maternal stress or pain during the procedure,” they added. “Appropriate safety measures including eye protection and laser plume management should continue to be used during laser treatment.”
The authors reported no funding sources or conflicts of interest.
SOURCE: Wilkerson EJ et al. Dermatol Surg. 2019 Jun;45(6):818-28.
according to the results of a systematic review of 22 studies.
Among 380 women in all trimesters of pregnancy who were treated with various laser wavelengths, the only clinically significant event was a case of premature rupture of membranes (PROM) “without further morbidity,” wrote Eric C. Wilkerson, MD, of Skin Laser & Surgery Specialists of NY and NJ in New York, and associates. In that case, the cause was not clear, there was no further morbidity, “and it was uncertain whether this was related to the laser procedure.”
However, only 22 studies were identified between 1960 and 2017, all of which were case reports or series, published from 1994 to 2015. “[Thus far,] the best evidence exists for the safety of the carbon dioxide laser, particularly in the treatment of condyloma,” they wrote in Dermatologic Surgery.
Elective laser treatments are usually not recommended during pregnancy, but no evidence supports this, Dr. Wilkerson and coauthors wrote. Therefore, they searched for studies indexed in PubMed, Google Scholar, the Cochrane Library, or the EBSCO CINAHL Plus Database from 1960 to 2017. They also searched LexisNexis for relevant legal cases, but found none.
The women in the 22 case reports and series were aged 14-41 years and received laser therapy for cervical adenocarcinoma, urolithiasis, condyloma acuminata, cervical carcinoma in situ, cutaneous scarring, Buschke-Löwenstein tumor, verrucous carcinoma, and acne vulgaris. Modalities included 504-nm pulsed-dye laser, 532-nm potassium titanyl phosphate, 1,064-nm neodymium:YAG, 2,100-nm holmium:YAG, and 10,600-nm CO2.
Apart from the case of PROM, there were no instances of fetal morbidity or mortality, premature labor or preterm birth, or detectable fetal stress, the authors wrote. The case of PROM occurred at 35 weeks, 4 days after the mother had received CO2 laser therapy for condyloma acuminata. She delivered normally approximately 1 week later. There also were several cases of premature contractions without true labor, all of which responded to tocolytic therapy. (In the same study, there also were two cases of PROM in women 7 and 10 weeks after the same procedure, but were thought to be unrelated.)
The thickness of the pregnant abdomen, uterus, and amniotic fluid makes it “very unlikely” that clinically significant amounts of laser energy would reach the fetus during cutaneous laser therapy, the authors noted. Certain topical anesthetics, such as lidocaine and prilocaine, also appear safe during pregnancy “and may potentially decrease concern for fetal stress secondary to maternal stress or pain during the procedure,” they added. “Appropriate safety measures including eye protection and laser plume management should continue to be used during laser treatment.”
The authors reported no funding sources or conflicts of interest.
SOURCE: Wilkerson EJ et al. Dermatol Surg. 2019 Jun;45(6):818-28.
according to the results of a systematic review of 22 studies.
Among 380 women in all trimesters of pregnancy who were treated with various laser wavelengths, the only clinically significant event was a case of premature rupture of membranes (PROM) “without further morbidity,” wrote Eric C. Wilkerson, MD, of Skin Laser & Surgery Specialists of NY and NJ in New York, and associates. In that case, the cause was not clear, there was no further morbidity, “and it was uncertain whether this was related to the laser procedure.”
However, only 22 studies were identified between 1960 and 2017, all of which were case reports or series, published from 1994 to 2015. “[Thus far,] the best evidence exists for the safety of the carbon dioxide laser, particularly in the treatment of condyloma,” they wrote in Dermatologic Surgery.
Elective laser treatments are usually not recommended during pregnancy, but no evidence supports this, Dr. Wilkerson and coauthors wrote. Therefore, they searched for studies indexed in PubMed, Google Scholar, the Cochrane Library, or the EBSCO CINAHL Plus Database from 1960 to 2017. They also searched LexisNexis for relevant legal cases, but found none.
The women in the 22 case reports and series were aged 14-41 years and received laser therapy for cervical adenocarcinoma, urolithiasis, condyloma acuminata, cervical carcinoma in situ, cutaneous scarring, Buschke-Löwenstein tumor, verrucous carcinoma, and acne vulgaris. Modalities included 504-nm pulsed-dye laser, 532-nm potassium titanyl phosphate, 1,064-nm neodymium:YAG, 2,100-nm holmium:YAG, and 10,600-nm CO2.
Apart from the case of PROM, there were no instances of fetal morbidity or mortality, premature labor or preterm birth, or detectable fetal stress, the authors wrote. The case of PROM occurred at 35 weeks, 4 days after the mother had received CO2 laser therapy for condyloma acuminata. She delivered normally approximately 1 week later. There also were several cases of premature contractions without true labor, all of which responded to tocolytic therapy. (In the same study, there also were two cases of PROM in women 7 and 10 weeks after the same procedure, but were thought to be unrelated.)
The thickness of the pregnant abdomen, uterus, and amniotic fluid makes it “very unlikely” that clinically significant amounts of laser energy would reach the fetus during cutaneous laser therapy, the authors noted. Certain topical anesthetics, such as lidocaine and prilocaine, also appear safe during pregnancy “and may potentially decrease concern for fetal stress secondary to maternal stress or pain during the procedure,” they added. “Appropriate safety measures including eye protection and laser plume management should continue to be used during laser treatment.”
The authors reported no funding sources or conflicts of interest.
SOURCE: Wilkerson EJ et al. Dermatol Surg. 2019 Jun;45(6):818-28.
FROM DERMATOLOGIC SURGERY
Colorectal cancer screening: Choosing the right test
Screening can help prevent colorectal cancer. The United States has seen a steady decline in colorectal cancer incidence and mortality, thanks in large part to screening. Screening rates can be increased with good patient-physician dialogue and by choosing a method the patient prefers and is most likely to complete.
In this article, we review a general approach to screening, focusing on the most commonly used methods in the United States, ie, the guaiac-based fecal occult blood test (FOBT), the fecal immunochemical test (FIT), and colonoscopy. We discuss current colorectal cancer incidence rates, screening recommendations, and how to choose the appropriate screening test.
This article does not discuss patients at high risk of polyps or cancer due to hereditary colon cancer syndromes, a personal history of colorectal neoplasia, inflammatory bowel disease, or primary sclerosing cholangitis.
TRENDS IN INCIDENCE
Colorectal cancer is the second most common type of cancer and cause of cancer-related deaths in the United States, responsible for an estimated 50,000 deaths in 2017. The lifetime risk of its occurrence is estimated to be 1 in 21 men and 1 in 23 women.1 Encouragingly, the incidence has declined by 24% over the last 30 years,2 and by 3% per year from 2004 to 2013.1 Also, as a result of screening and advances in treatment, 5-year survival rates for patients with colorectal cancer have increased, from 48.6% in 1975 to 66.4% in 2009.2
When detected at a localized stage, the 5-year survival rate in colorectal cancer is greater than 90%. Unfortunately, it is diagnosed early in only 39% of patients. And despite advances in treatment and a doubling of the 5-year survival rate in patients with advanced cancers since 1990,3 the latter is only 14%. In most patients, cancer is diagnosed when it has spread to the lymph nodes (36%) or to distant organs (22%), and the survival rate declines to 71% after lymph-node spread, and 14% after metastasis to distant organs.
It is essential to screen people who have no symptoms, as symptoms such as gastrointestinal bleeding, unexplained abdominal pain or weight loss, a persistent change in bowel movements, and bowel obstruction typically do not arise until the disease is advanced and less amenable to cure.
Increasing prevalence in younger adults
Curiously, the incidence of colorectal cancer is increasing in white US adults under age 50. Over the last 30 years, incidence rates have increased from 1.0% to 2.4% annually in adults ages 20 to 39.4 Based on current trends, colon cancer rates are expected to increase by 90% for patients ages 20 to 34 and by 28% for patients 35 to 49 by 2030.5
Although recommendations vary for colorectal cancer screening in patients under age 50, clinicians should investigate symptoms such as rectal bleeding, unexplained iron deficiency anemia, progressive abdominal pain, and persistent changes in bowel movements.
Other challenges
Despite the benefits of screening, it is underutilized. Although rates of compliance with screening recommendations have increased 10% over the last 10 years, only 65% of eligible adults currently comply.1,6
Additionally, certain areas of the country such as Appalachia and the Mississippi Delta have not benefited from the decline in the national rate of colorectal cancer.7
SCREENING GUIDELINES
Most guidelines say that colorectal cancer screening should begin at age 50 in people at average risk with no symptoms. However, the American College of Gastroenterology (ACG) recommends beginning screening at age 45 in African Americans, as this group has higher incidence and mortality rates of colorectal cancer.8 Also, the American Cancer Society recently recommended beginning screening at age 45 for all individuals.9
Screening can stop at age 75 for most patients, according to the ACG,8 the US Multi-Society Task Force on Colorectal Cancer,10 and the US Preventive Services Task Force (USPSTF).11 However, the decision should be individualized for patients ages 76 to 85. Patients within that age group who are in good health and have not previously been screened are more likely to benefit than those who have previously been screened and had a negative screening test. Patients over age 85 should not begin or continue screening, because of diminished benefit of screening in this age group, shorter life expectancy, advanced comorbid conditions, and the risks of colonoscopy and cancer treatment.
Patients and clinicians are encouraged to collaborate in deciding which screening method is appropriate. Patients adhere better when they are given a choice in the matter.12–14 And adherence is the key to effective colorectal cancer screening.
Familiarity with the key characteristics of currently available colorectal cancer screening tests will facilitate discussion with patients.
Opportunistic vs programmatic screening
Screening can be classified according to the approach to the patient or population and the intent of the test. Most screening in the United States is opportunistic rather than programmatic—that is, the physician offers the patient screening at the point of service without systematic follow-up or patient re-engagement.
In a programmatic approach, the patient is offered screening through an organized program that streamlines services, reduces overscreening, and provides systematic follow-up of testing.
DISCUSSING THE OPTIONS
Stool studies such as FOBT and FIT do not reliably detect cancer precursors such as adenomas and serrated neoplasms. If an FOBT is positive, follow-up diagnostic colonoscopy is required. Unlike screening colonoscopy, diagnostic colonoscopy requires a copayment for Medicare patients, and this should be explained to the patient.
FIT and FOBT detect hemolyzed blood within a stool sample, FOBT by a chemical reaction, and FIT by detecting a globin-specific antibody. Colorectal cancer and some large adenomatous polyps may intermittently bleed and result in occult blood in the stool, iron deficiency anemia, or hematochezia.15
Fecal occult blood testing
Historically, FOBT was the stool test of choice for screening. It uses an indirect enzymatic reaction to detect hemolyzed blood in the stool. When a specimen containing hemoglobin is added to guaiac paper and a drop of hydrogen peroxide is added to “develop” it, the peroxidase activity of hemoglobin turns the guaiac blue.
Screening with FOBT involves annual testing of 3 consecutively passed stools from different days; FOBT should not be performed at the time of digital rectal examination or if the patient is having overt rectal, urinary, or menstrual bleeding.
Dietary and medication restrictions before and during the testing period are critical, as red meat contains hemoglobin, and certain vegetables (eg, radishes, turnips, cauliflower, cucumbers) contain peroxidase, all of which can cause a false-positive result. Waiting 3 days after the stool sample is collected to develop it can mitigate the peroxidase activity of vegetables.16 Vitamin C inhibits heme peroxidase activity and leads to false-negative results. Aspirin and high-dose nonsteroidal anti-inflammatory drugs can promote bleeding throughout the intestinal tract.17
In randomized controlled trials,18–21 screening with FOBT reduced colorectal cancer mortality rates by 15% to 33%. The 30-year follow-up of a large US trial22 found a 32% relative reduction in mortality rates in patients randomized to annual screening, and a 22% relative reduction in those randomized to screening every 2 years. Despite the many possibilities for false-positive results, the specificity for detecting cancer has ranged from 86.7% to 97.3%, and the sensitivity from 37.1% to 79.4%, highlighting the benefit of colorectal cancer screening programs in unscreened populations.23–26
FIT vs FOBT in current practice
FIT should replace FOBT as the preferred stool screening method. Instead of an enzymatic reaction that can be altered by food or medication, FIT utilizes an antibody specific to human globin to directly detect hemolyzed blood, thus eliminating the need to modify the diet or medications.27 Additionally, only 1 stool specimen is needed, which may explain why the adherence rate was about 20% higher with FIT than with FOBT in most studies.28–30
FIT has a sensitivity of 69% to 86% for colorectal cancer and a specificity of 92% to 95%.31 The sensitivity can be improved by lowering the threshold value for a positive test, but this is associated with a decrease in specificity. A single FIT has the same sensitivity and specificity as several samples.32
In a large retrospective US cohort study of programmatic screening with FIT, Jensen et al33 reported that 48% of 670,841 people who were offered testing actually did the test. Of the 48% who participated in the first round and remained eligible, 75% to 86% participated in subsequent rounds over 4 years. Those who had a positive result on FIT were supposed to undergo colonoscopy, but 22% did not.
The US Multi-Society Task Force on Colorectal Cancer34 suggests that FIT-based screening programs aim for a target FIT completion rate of more than 60% and a target colonoscopy completion rate of more than 80% of patients with positive FITs. These benchmarks were derived from adherence rates in international FIT screening studies in average-risk populations.35–39 (Note that the large US cohort described above33 did not meet these goals.) Ideally, every patient with a positive FIT should undergo diagnostic colonoscopy, but in reality only 50% to 83% actually do. Methods shown to improve adherence include structured screening programs with routine performance reports, provider feedback, and involvement of patient navigators.40–42
Accordingly, several aspects of stool-based testing need to be stressed with patients. Understanding that FOBT is recommended yearly is integral for optimal impact on colorectal cancer incidence and mortality rates.
Additionally, patients should be advised to undergo colonoscopy soon after a positive FIT, because delaying colonoscopy could give precancerous lesions time to progress in stage. The acceptable time between a positive FIT and colonoscopy has yet to be determined. However, a retrospective cohort study of 1.26 million screened patients with 107,000 positive FIT results demonstrated that the rates of cancer discovered on colonoscopy were similar when performed within 30 days or up to 10 months after a positive test. Detection rates increased from 3% to 4.8% at 10 months and to 7.9% at 12 months.43
In modeling studies, Meester et al44 showed the estimated lifetime risk and mortality rates from colorectal cancer and life-years gained from screening are significantly better when colonoscopy is completed within 2 weeks rather than 1 year after a positive FIT. Each additional month after 2 weeks incrementally affected these outcomes, with a 1.4% increase in cancer mortality. These data suggest that colonoscopy should be done soon after a positive FIT result and at a maximum of 10 months.43,44
Screening with FOBT is a multistep process for patients that includes receiving the test kit, collecting the sample, preparing it, returning it, undergoing colonoscopy after a positive test, and repeating in 1 year if negative. The screening program should identify patients at average risk in whom screening is appropriate, ensure delivery of the test, verify the quality of collected samples for laboratory testing against the manufacturer’s recommendations, and report results. Report of a positive FOBT result should provide recommendations for follow-up.
Though evidence clearly supports screening annually or biennially (every 2 years) with FOBT, the ideal interval for FIT is undetermined. Modeling studies utilized by the USPSTF and Multi-Society Task Force demonstrate that colonoscopy and annual FIT result in similar life-years gained, while 2 population-based screening programs have demonstrated that a 2- or 3-year interval may be equally efficacious by lowering the threshold for a positive test.38,45
Randomized controlled trials of screening colonoscopy vs annual and biennial FIT are currently under way. Cost-effectiveness analysis has shown that offering single-sample FITs at more frequent (annual) intervals performs better than multisample testing at less frequent intervals.45–47
Colonoscopy
Compared with stool-based screening, colonoscopy has advantages, including a 10-year screening interval if bowel preparation is adequate and the examination shows no neoplasia, the ability to inspect the entire colon, and the ability to diagnose and treat lesions in the same session.
Screening colonoscopy visualizes the entire colon in more than 98% of cases, although it requires adequate bowel preparation for maximal polyp detection. It can be done safely with or without sedation.48
While there are no available randomized controlled trial data on the impact of screening colonoscopy on cancer incidence or mortality, extensive case-control and cohort studies consistently show that screening colonoscopy reduces cancer incidence and mortality rates.49–54 A US Veterans Administration study of more than 32,000 patients reported a 50% reduction in overall colorectal cancer mortality.55 In a microsimulation modeling study that assumed 100% adherence, colonoscopy every 10 years and annual FIT in individuals ages 50 to 75 provided similar life-years gained per 1,000 people screened (270 for colonoscopy, 244 for FIT).56
Well-established metrics for maximizing the effectiveness and quality of colonoscopy have been established (Table 2). The most important include the mucosa inspection time (withdrawal time) and adenoma detection rate.57 Withdrawal time is directly correlated with adenoma detection, and a 6-minute minimum withdrawal time is recommended in screening colonoscopy examinations of patients at average risk when no polyps are found.58 The adenoma detection rate is the strongest evidence-based metric, as each 1% increase in the adenoma detection rate over 19% is associated with a 3% decrease in the risk of colorectal cancer and a 5% decrease in death rate.59 The average-risk screening adenoma detection rate differs based on sex: the rate is greater than 20% for women and greater than 30% for men.
Complications from screening, diagnostic, or therapeutic colonoscopy are infrequent but include perforation (4/10,000) and significant intestinal bleeding (8/10,000).56–62
Patients with a first-degree relative under age 60 with advanced adenomas or colorectal cancer are considered at high risk and should begin screening colonoscopy at age 40, with repeat colonoscopy at 5-year intervals, given a trend toward advanced neoplasia detection compared with FIT.63
Guidelines recently published by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association also support starting screening in high-risk individuals at age 40, with a surveillance interval of 5 to 10 years based on the number of first-degree relatives with colorectal cancer or adenomas.64 Consensus statements were based on retrospective cohort, prospective case-controlled, and cross-sectional studies comparing the risk of colorectal cancer in individuals with a family history against those without a family history.
Randomized clinical trials comparing colonoscopy and FIT are under way. Interim analysis of a European trial in which asymptomatic adults ages 50 to 69 were randomized to 1-time colonoscopy (26,703 patients) vs FIT every 2 years (26,599 patients) found significantly higher participation rates in the FIT arm (34.2% vs 24.6%) but higher rates of nonadvanced adenomas (4.2% vs 0.4%) and advanced neoplasia (1.9% vs 0.9%) in the colonoscopy arm.65 Cancer was detected in 0.1% in each arm. These findings correlate with those of another study showing higher participation with FIT but higher advanced neoplasia detection rates with colonoscopy.66
Detection of precursor lesions is vital, as removing neoplasms is the main strategy to reduce colorectal cancer incidence. Accordingly, the advantage of colonoscopy was illustrated by a study that determined that 53 patients would need to undergo screening colonoscopy to detect 1 advanced adenoma or cancerous lesion, compared with 264 for FIT.67
STARTING SCREEING AT AGE 45
The American Cancer Society recently provided a qualified recommendation to start colorectal cancer screening in all individuals at age 45 rather than 50.9 This recommendation was based on modeling studies demonstrating that starting screening at age 45 with colonoscopy every 10 years resulted in 25 life-years gained at the cost of 610 colonoscopies per 1,000 individuals. Alternative strategies included FIT, which resulted in an additional 26 life-years gained per 1,000 individuals screened, flexible sigmoidoscopy (23 life-years gained), and computed tomographic colonoscopy (22 life-years gained).
Rates of colorectal cancer are rising in adults under age 50, and 10,000 new cases are anticipated this year.2,3 Currently, 22 million US adults are between the ages of 45 and 50. The system and support needed to perform screening in all adults over age 45 and a lack of direct evidence to support its benefits in the young population need to be considered before widespread acceptance of the American Cancer Society recommendations. However, if screening is considered, FIT with or without sigmoidoscopy may be appropriate, given that most cancers diagnosed in individuals under age 50 are left-sided.4,5
Screening has not been proven to reduce all-cause mortality. Randomized controlled trials of FOBT and observational studies of colonoscopy show that screening reduces cancer incidence and mortality. Until the currently ongoing randomized controlled trials comparing colonoscopy with FIT are completed, their comparative impact on colorectal cancer end points is unknown.
PATIENT ADHERENCE IS KEY
FIT and colonoscopy are the most prevalent screening methods in the United States. Careful attention should be given to offer the screening option the patient is most likely to complete, as adherence is key to the benefit from colorectal cancer screening.
The National Colorectal Cancer Roundtable (nccrt.org), established in 1997 by the American Cancer Society and the US Centers for Disease Control and Prevention, is a national coalition of public and private organizations dedicated to reducing colorectal cancer incidence and mortality. The Roundtable waged a national campaign to achieve a colorectal cancer screening rate of 80% in eligible adults by 2018, a goal that was not met. Still, the potential for a substantial impact is a compelling reason to endorse adherence to colorectal cancer screening. The Roundtable provides many resources for physicians to enhance screening in their practice.
The United States has seen a steady decline in colorectal cancer incidence and mortality, mainly as a result of screening. Colorectal cancer is preventable with ensuring patients’ adherence to screening. Screening rates have been shown to increase with patient-provider dialogue and with selection of a screening program the patient prefers and is most likely to complete.
- American Cancer Society. Colorectal Cancer Facts & Figures 2017–2019. Atlanta: American Cancer Society; 2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2017-2019.pdf. Accessed April 1, 2019.
- Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin 2017; 67(3):177–193. doi:10.3322/caac.21395
- Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 2009; 27(22):3677–3683. doi:10.1200/JCO.2008.20.5278
- Siegel RL, Jemal A, Ward EM. Increase in incidence of colorectal cancer among young men and women in the United States. Cancer Epidemiol Biomarkers Prev 2009; 18(6):1695–1698. doi:10.1158/1055-9965.EPI-09-0186
- Bailey CE, Hu CY, You YN, et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg 2015; 150(1):17–22. doi:10.1001/jamasurg.2014.1756
- Centers for Disease Control and Prevention (CDC). Vital signs: colorectal cancer screening test use—United States, 2012. MMWR Morb Mortal Wkly Rep 2013; 62(44):881–888. pmid:24196665
- Siegel RL, Sahar L, Robbins A, Jemal A. Where can colorectal cancer screening interventions have the most impact? Cancer Epidemiol Biomarkers Prev 2015; 24(8):1151–1156. doi:10.1158/1055-9965.EPI-15-0082
- Agrawal S, Bhupinderjit A, Bhutani MS, et al; Committee of Minority Affairs and Cultural Diversity, American College of Gastroenterology. Colorectal cancer in African Americans. Am J Gastroenterol 2005; 100(3):515–523. doi:10.1111/j.1572-0241.2005.41829.x
- Wolf AMD, Fontham ETH, Church TR, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin 2018; 68(4):250–281. doi:10.3322/caac.21457
- Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: recommendations for physicians and patients from the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2017; 112(7):1016–1030. doi:10.1038/ajg.2017.174
- US Preventive Services Task Force; Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for colorectal cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2016; 315(23):2564–2575. doi:10.1001/jama.2016.5989
- Inadomi JM, Vijan S, Janz NK, et al. Adherence to colorectal cancer screening: a randomized clinical trial of competing strategies. Arch Intern Med 2012; 172(7):575–582. doi:10.1001/archinternmed.2012.332
- Steinwachs D, Allen JD, Barlow WE, et al. National Institutes of Health state-of-the-science conference statement: enhancing use and quality of colorectal cancer screening. Ann Intern Med 2010; 152(10):663–667. doi:10.7326/0003-4819-152-10-201005180-00237
- Subramanian S, Klosterman M, Amonkar MM, Hunt TL. Adherence with colorectal cancer screening guidelines: a review. Prev Med 2004; 38(5):536–550. doi:10.1016/j.ypmed.2003.12.011
- Levin B, Lieberman DA, McFarland B, et al; American Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin 2008; 58(3):130–160. doi:10.3322/CA.2007.0018
- Sinatra MA, St John DJ, Young GP. Interference of plant peroxidases with guaiac-based fecal occult blood tests is avoidable. Clin Chem 1999; 45(1):123–126. pmid:9895348
- Allison JE, Sakoda LC, Levin TR, et al. Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst 2007; 99(19):1462–1470. doi:10.1093/jnci/djm150
- Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328(19):1365–1371. doi:10.1056/NEJM199305133281901
- Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348(9040):1472–1477. doi:10.1016/S0140-6736(96)03386-7
- Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996; 348(9040):1467–1471. doi:10.1016/S0140-6736(96)03430-7
- Wilson JMG, Junger G. Principles and practice of screening for disease. Geneva, Switzerland: World Health Organization; 1968. http://apps.who.int/iris/bitstream/handle/10665/37650/WHO_PHP_34.pdf?sequence=17. Accessed April 1, 2019.
- Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med 2013; 369(12):1106–1114. doi:10.1056/NEJMoa1300720
- Allison JE, Tekawa IS, Ransom LJ, Adrain AL. A comparison of fecal occult-blood tests for colorectal-cancer screening. N Engl J Med 1996; 334(3):155–159. doi:10.1056/NEJM199601183340304
- Shapiro JA, Bobo JK, Church TR, et al. A comparison of fecal immunochemical and high-sensitivity guaiac tests for colorectal cancer screening. Am J Gastroenterol 2017; 112(11):1728–1735. doi:10.1038/ajg.2017.285
- Smith A, Young GP, Cole SR, Bampton P. Comparison of a brush-sampling fecal immunochemical test for hemoglobin with a sensitive guaiac-based fecal occult blood test in detection of colorectal neoplasia. Cancer 2006; 107(9):2152–2159. doi:10.1002/cncr.22230
- Brenner H, Tao S. Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy. Eur J Cancer 2013; 49(14):3049–3054. doi:10.1016/j.ejca.2013.04.023
- Young GP, Cole S. New stool screening tests for colorectal cancer. Digestion 2007; 76(1):26–33. doi:10.1159/000108391
- van Rossum LG, van Rijn AF, Laheij RJ, et al. Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population. Gastroenterology 2008; 135(1):82–90. doi:10.1053/j.gastro.2008.03.040
- Hassan C, Giorgi Rossi P, Camilloni L, et al. Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test. Aliment Pharmacol Ther 2012; 36(10):929–940. doi:10.1111/apt.12071
- Vart G, Banzi R, Minozzi S. Comparing participation rates between immunochemical and guaiac faecal occult blood tests: a systematic review and meta-analysis. Prev Med 2012; 55(2):87–92. doi:10.1016/j.ypmed.2012.05.006
- Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med 2014; 370(14):1287–1297. doi:10.1056/NEJMoa1311194
- Lee JK, Liles EG, Bent S, Levin TR, Corley DA. Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis. Ann Intern Med 2014; 160(3):171. doi:10.7326/M13-1484
- Jensen CD, Corley DA, Quinn VP, et al. Fecal immunochemical test program performance over 4 rounds of annual screening: a retrospective cohort study. Ann Intern Med 2016; 164(7):456–463. doi:10.7326/M15-0983
- Robertson DJ, Lee JK, Boland CR, et al. Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2017; 152(5):1217–1237.e3. doi:10.1053/j.gastro.2016.08.053
- Rabeneck L, Rumble RB, Thompson F, et al. Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening. Can J Gastroenterol 2012; 26(3):131–147. pmid:22408764
- Logan RF, Patnick J, Nickerson C, Coleman L, Rutter MD, von Wagner C; English Bowel Cancer Screening Evaluation Committee. Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests. Gut 2012; 61(10):1439–1446. doi:10.1136/gutjnl-2011-300843
- Malila N, Oivanen T, Malminiemi O, Hakama M. Test, episode, and programme sensitivities of screening for colorectal cancer as a public health policy in Finland: experimental design. BMJ 2008; 337:a2261. doi:10.1136/bmj.a2261
- Denters MJ, Deutekom M, Bossuyt PM, Stroobants AK, Fockens P, Dekker E. Lower risk of advanced neoplasia among patients with a previous negative result from a fecal test for colorectal cancer. Gastroenterology 2012; 142(3):497–504. doi:10.1053/j.gastro.2011.11.024
- van Roon AH, Goede SL, van Ballegooijen M, et al. Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening. Gut 2013; 62(3):409–415. doi:10.1136/gutjnl-2011-301583
- Chubak J, Garcia MP, Burnett-Hartman AN, et al; PROSPR consortium. Time to colonoscopy after positive fecal blood test in four US health care systems. Cancer Epidemiol Biomarkers Prev 2016; 25(2):344–350. doi:10.1158/1055-9965.EPI-15-0470
- Carlson CM, Kirby KA, Casadei MA, Partin MR, Kistler CE, Walter LC. Lack of follow-up after fecal occult blood testing in older adults: inappropriate screening or failure to follow up? Arch Intern Med 2011; 171(3):249–256. doi:10.1001/archinternmed.2010.372
- Selby K, Baumgartner C, Levin TR, et al. Interventions to improve follow-up of positive results on fecal blood tests: a systematic review. Ann Intern Med 2017; 167(8):565–575. doi:10.7326/M17-1361
- Corley DA, Jensen CD, Quinn VP, et al. Association between time to colonoscopy after a positive fecal test result and risk of colorectal cancer and cancer stage at diagnosis. JAMA 2017; 317(16):1631–1641. doi:10.1001/jama.2017.3634
- Meester RG, Zauber AG, Doubeni CA, et al. Consequences of increasing time to colonoscopy examination after positive result from fecal colorectal cancer screening test. Clin Gastroenterol Hepatol 2016; 14(10):1445–1451.e8. doi:10.1016/j.cgh.2016.05.017
- Haug U, Grobbee EJ, Lansdorp-Vogelaar I, Spaander MCW, Kuipers EJ. Immunochemical faecal occult blood testing to screen for colorectal cancer: can the screening interval be extended? Gut 2017; 66(7):1262–1267. doi:10.1136/gutjnl-2015-310102
- Goede SL, van Roon AH, Reijerink JC, et al. Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening. Gut 2013; 62(5):727–734. doi:10.1136/gutjnl-2011-301917
- Digby J, Fraser CG, Carey FA, Steele RJC. Can the performance of a quantitative FIT-based colorectal cancer screening programme be enhanced by lowering the threshold and increasing the interval? Gut 2018; 67(5):993–994. doi:10.1136/gutjnl-2017-314862
- Hoffman MS, Butler TW, Shaver T. Colonoscopy without sedation. J Clin Gastroenterol 1998; 26(4):279–282. pmid:9649011
- Zauber AG, Winawer SJ, O’Brien MJ, et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 2012; 366(8):687–696. doi:10.1056/NEJMoa1100370
- Nishihara R, Wu K, Lochhead P, et al. Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 2013; 369(12):1095–1105. doi:10.1056/NEJMoa1301969
- Løberg M, Kalager M, Holme Ø, Hoff G, Adami HO, Bretthauer M. Long-term colorectal-cancer mortality after adenoma removal. N Engl J Med 2014; 371(9):799–807. doi:10.1056/NEJMoa1315870
- Manser CN, Bachmann LM, Brunner J, Hunold F, Bauerfeind P, Marbet UA. Colonoscopy screening markedly reduces the occurrence of colon carcinomas and carcinoma-related death: a closed cohort study. Gastrointest Endosc 2012; 76(1):110–117. doi:10.1016/j.gie.2012.02.040
- Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993; 329(27):1977–1981. doi:10.1056/NEJM199312303292701
- Citarda F, Tomaselli G, Capocaccia R, Barcherini S, Crespi M; Italian Multicentre Study Group. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence. Gut 2001; 48(6):812–815. pmid:11358901
- Muller AD, Sonnenberg A. Prevention of colorectal cancer by flexible endoscopy and polypectomy. A case-control study of 32,702 veterans. Ann Intern Med 1995; 123(12):904–910. pmid:7486484
- Knudsen AB, Zauber AG, Rutter CM, et al. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA 2016; 315(23):2595–2609. doi:10.1001/jama.2016.6828
- Rex DK, Schoenfeld PS, Cohen J, et al. Quality indicators for colonoscopy. Gastrointest Endosc 2015; 81(1):31–53. doi:10.1016/j.gie.2014.07.058
- Barclay RL, Vicari JJ, Doughty AS, Johanson JF, Greenlaw RL. Colonoscopic withdrawal times and adenoma detection during screening colonoscopy. N Engl J Med 2006; 355(24):2533–2541. doi:10.1056/NEJMoa055498
- Corley DA, Levin TR, Doubeni CA. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med 2014; 370(26):2541. doi:10.1056/NEJMc1405329
- Lin JS, Piper MA, Perdue LA, et al. Screening for colorectal cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016; 315(23):2576–2594. doi:10.1001/jama.2016.3332
- Gatto NM, Frucht H, Sundararajan V, Jacobson JS, Grann VR, Neugut AI. Risk of perforation after colonoscopy and sigmoidoscopy: a population-based study. J Natl Cancer Inst 2003; 95(3):230–236. pmid:12569145
- Warren JL, Klabunde CN, Mariotto AB, et al. Adverse events after outpatient colonoscopy in the Medicare population. Ann Intern Med 2009; 150(12):849–857, W152. pmid:19528563
- Quintero E, Carrillo M, Gimeno-García AZ, et al. Equivalency of fecal immunochemical tests and colonoscopy in familial colorectal cancer screening. Gastroenterology 2014; 147(5):1021–130.e1. doi:10.1053/j.gastro.2014.08.004
- Leddin D, Lieberman DA, Tse F, et al. Clinical practice guideline on screening for colorectal cancer in individuals with a family history of nonhereditary colorectal cancer or adenoma: the Canadian Association of Gastroenterology Banff Consensus. Gastroenterology 2018; 155(5):1325–1347.e3. doi:10.1053/j.gastro.2018.08.017
- Quintero E, Castells A, Bujanda L, et al; COLONPREV Study Investigators. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med 2012; 366(8):697–706. doi:10.1056/NEJMoa1108895
- Gupta S, Halm EA, Rockey DC, et al. Comparative effectiveness of fecal immunochemical test outreach, colonoscopy outreach, and usual care for boosting colorectal cancer screening among the underserved: a randomized clinical trial. JAMA Intern Med 2013; 173(18):1725–1732. doi:10.1001/jamainternmed.2013.9294
- Segnan N, Senore C, Andreoni B, et al; SCORE3 Working Group-Italy. Comparing attendance and detection rate of colonoscopy with sigmoidoscopy and FIT for colorectal cancer screening. Gastroenterology 2007; 132(7):2304–2312. doi:10.1053/j.gastro.2007.03.030
Screening can help prevent colorectal cancer. The United States has seen a steady decline in colorectal cancer incidence and mortality, thanks in large part to screening. Screening rates can be increased with good patient-physician dialogue and by choosing a method the patient prefers and is most likely to complete.
In this article, we review a general approach to screening, focusing on the most commonly used methods in the United States, ie, the guaiac-based fecal occult blood test (FOBT), the fecal immunochemical test (FIT), and colonoscopy. We discuss current colorectal cancer incidence rates, screening recommendations, and how to choose the appropriate screening test.
This article does not discuss patients at high risk of polyps or cancer due to hereditary colon cancer syndromes, a personal history of colorectal neoplasia, inflammatory bowel disease, or primary sclerosing cholangitis.
TRENDS IN INCIDENCE
Colorectal cancer is the second most common type of cancer and cause of cancer-related deaths in the United States, responsible for an estimated 50,000 deaths in 2017. The lifetime risk of its occurrence is estimated to be 1 in 21 men and 1 in 23 women.1 Encouragingly, the incidence has declined by 24% over the last 30 years,2 and by 3% per year from 2004 to 2013.1 Also, as a result of screening and advances in treatment, 5-year survival rates for patients with colorectal cancer have increased, from 48.6% in 1975 to 66.4% in 2009.2
When detected at a localized stage, the 5-year survival rate in colorectal cancer is greater than 90%. Unfortunately, it is diagnosed early in only 39% of patients. And despite advances in treatment and a doubling of the 5-year survival rate in patients with advanced cancers since 1990,3 the latter is only 14%. In most patients, cancer is diagnosed when it has spread to the lymph nodes (36%) or to distant organs (22%), and the survival rate declines to 71% after lymph-node spread, and 14% after metastasis to distant organs.
It is essential to screen people who have no symptoms, as symptoms such as gastrointestinal bleeding, unexplained abdominal pain or weight loss, a persistent change in bowel movements, and bowel obstruction typically do not arise until the disease is advanced and less amenable to cure.
Increasing prevalence in younger adults
Curiously, the incidence of colorectal cancer is increasing in white US adults under age 50. Over the last 30 years, incidence rates have increased from 1.0% to 2.4% annually in adults ages 20 to 39.4 Based on current trends, colon cancer rates are expected to increase by 90% for patients ages 20 to 34 and by 28% for patients 35 to 49 by 2030.5
Although recommendations vary for colorectal cancer screening in patients under age 50, clinicians should investigate symptoms such as rectal bleeding, unexplained iron deficiency anemia, progressive abdominal pain, and persistent changes in bowel movements.
Other challenges
Despite the benefits of screening, it is underutilized. Although rates of compliance with screening recommendations have increased 10% over the last 10 years, only 65% of eligible adults currently comply.1,6
Additionally, certain areas of the country such as Appalachia and the Mississippi Delta have not benefited from the decline in the national rate of colorectal cancer.7
SCREENING GUIDELINES
Most guidelines say that colorectal cancer screening should begin at age 50 in people at average risk with no symptoms. However, the American College of Gastroenterology (ACG) recommends beginning screening at age 45 in African Americans, as this group has higher incidence and mortality rates of colorectal cancer.8 Also, the American Cancer Society recently recommended beginning screening at age 45 for all individuals.9
Screening can stop at age 75 for most patients, according to the ACG,8 the US Multi-Society Task Force on Colorectal Cancer,10 and the US Preventive Services Task Force (USPSTF).11 However, the decision should be individualized for patients ages 76 to 85. Patients within that age group who are in good health and have not previously been screened are more likely to benefit than those who have previously been screened and had a negative screening test. Patients over age 85 should not begin or continue screening, because of diminished benefit of screening in this age group, shorter life expectancy, advanced comorbid conditions, and the risks of colonoscopy and cancer treatment.
Patients and clinicians are encouraged to collaborate in deciding which screening method is appropriate. Patients adhere better when they are given a choice in the matter.12–14 And adherence is the key to effective colorectal cancer screening.
Familiarity with the key characteristics of currently available colorectal cancer screening tests will facilitate discussion with patients.
Opportunistic vs programmatic screening
Screening can be classified according to the approach to the patient or population and the intent of the test. Most screening in the United States is opportunistic rather than programmatic—that is, the physician offers the patient screening at the point of service without systematic follow-up or patient re-engagement.
In a programmatic approach, the patient is offered screening through an organized program that streamlines services, reduces overscreening, and provides systematic follow-up of testing.
DISCUSSING THE OPTIONS
Stool studies such as FOBT and FIT do not reliably detect cancer precursors such as adenomas and serrated neoplasms. If an FOBT is positive, follow-up diagnostic colonoscopy is required. Unlike screening colonoscopy, diagnostic colonoscopy requires a copayment for Medicare patients, and this should be explained to the patient.
FIT and FOBT detect hemolyzed blood within a stool sample, FOBT by a chemical reaction, and FIT by detecting a globin-specific antibody. Colorectal cancer and some large adenomatous polyps may intermittently bleed and result in occult blood in the stool, iron deficiency anemia, or hematochezia.15
Fecal occult blood testing
Historically, FOBT was the stool test of choice for screening. It uses an indirect enzymatic reaction to detect hemolyzed blood in the stool. When a specimen containing hemoglobin is added to guaiac paper and a drop of hydrogen peroxide is added to “develop” it, the peroxidase activity of hemoglobin turns the guaiac blue.
Screening with FOBT involves annual testing of 3 consecutively passed stools from different days; FOBT should not be performed at the time of digital rectal examination or if the patient is having overt rectal, urinary, or menstrual bleeding.
Dietary and medication restrictions before and during the testing period are critical, as red meat contains hemoglobin, and certain vegetables (eg, radishes, turnips, cauliflower, cucumbers) contain peroxidase, all of which can cause a false-positive result. Waiting 3 days after the stool sample is collected to develop it can mitigate the peroxidase activity of vegetables.16 Vitamin C inhibits heme peroxidase activity and leads to false-negative results. Aspirin and high-dose nonsteroidal anti-inflammatory drugs can promote bleeding throughout the intestinal tract.17
In randomized controlled trials,18–21 screening with FOBT reduced colorectal cancer mortality rates by 15% to 33%. The 30-year follow-up of a large US trial22 found a 32% relative reduction in mortality rates in patients randomized to annual screening, and a 22% relative reduction in those randomized to screening every 2 years. Despite the many possibilities for false-positive results, the specificity for detecting cancer has ranged from 86.7% to 97.3%, and the sensitivity from 37.1% to 79.4%, highlighting the benefit of colorectal cancer screening programs in unscreened populations.23–26
FIT vs FOBT in current practice
FIT should replace FOBT as the preferred stool screening method. Instead of an enzymatic reaction that can be altered by food or medication, FIT utilizes an antibody specific to human globin to directly detect hemolyzed blood, thus eliminating the need to modify the diet or medications.27 Additionally, only 1 stool specimen is needed, which may explain why the adherence rate was about 20% higher with FIT than with FOBT in most studies.28–30
FIT has a sensitivity of 69% to 86% for colorectal cancer and a specificity of 92% to 95%.31 The sensitivity can be improved by lowering the threshold value for a positive test, but this is associated with a decrease in specificity. A single FIT has the same sensitivity and specificity as several samples.32
In a large retrospective US cohort study of programmatic screening with FIT, Jensen et al33 reported that 48% of 670,841 people who were offered testing actually did the test. Of the 48% who participated in the first round and remained eligible, 75% to 86% participated in subsequent rounds over 4 years. Those who had a positive result on FIT were supposed to undergo colonoscopy, but 22% did not.
The US Multi-Society Task Force on Colorectal Cancer34 suggests that FIT-based screening programs aim for a target FIT completion rate of more than 60% and a target colonoscopy completion rate of more than 80% of patients with positive FITs. These benchmarks were derived from adherence rates in international FIT screening studies in average-risk populations.35–39 (Note that the large US cohort described above33 did not meet these goals.) Ideally, every patient with a positive FIT should undergo diagnostic colonoscopy, but in reality only 50% to 83% actually do. Methods shown to improve adherence include structured screening programs with routine performance reports, provider feedback, and involvement of patient navigators.40–42
Accordingly, several aspects of stool-based testing need to be stressed with patients. Understanding that FOBT is recommended yearly is integral for optimal impact on colorectal cancer incidence and mortality rates.
Additionally, patients should be advised to undergo colonoscopy soon after a positive FIT, because delaying colonoscopy could give precancerous lesions time to progress in stage. The acceptable time between a positive FIT and colonoscopy has yet to be determined. However, a retrospective cohort study of 1.26 million screened patients with 107,000 positive FIT results demonstrated that the rates of cancer discovered on colonoscopy were similar when performed within 30 days or up to 10 months after a positive test. Detection rates increased from 3% to 4.8% at 10 months and to 7.9% at 12 months.43
In modeling studies, Meester et al44 showed the estimated lifetime risk and mortality rates from colorectal cancer and life-years gained from screening are significantly better when colonoscopy is completed within 2 weeks rather than 1 year after a positive FIT. Each additional month after 2 weeks incrementally affected these outcomes, with a 1.4% increase in cancer mortality. These data suggest that colonoscopy should be done soon after a positive FIT result and at a maximum of 10 months.43,44
Screening with FOBT is a multistep process for patients that includes receiving the test kit, collecting the sample, preparing it, returning it, undergoing colonoscopy after a positive test, and repeating in 1 year if negative. The screening program should identify patients at average risk in whom screening is appropriate, ensure delivery of the test, verify the quality of collected samples for laboratory testing against the manufacturer’s recommendations, and report results. Report of a positive FOBT result should provide recommendations for follow-up.
Though evidence clearly supports screening annually or biennially (every 2 years) with FOBT, the ideal interval for FIT is undetermined. Modeling studies utilized by the USPSTF and Multi-Society Task Force demonstrate that colonoscopy and annual FIT result in similar life-years gained, while 2 population-based screening programs have demonstrated that a 2- or 3-year interval may be equally efficacious by lowering the threshold for a positive test.38,45
Randomized controlled trials of screening colonoscopy vs annual and biennial FIT are currently under way. Cost-effectiveness analysis has shown that offering single-sample FITs at more frequent (annual) intervals performs better than multisample testing at less frequent intervals.45–47
Colonoscopy
Compared with stool-based screening, colonoscopy has advantages, including a 10-year screening interval if bowel preparation is adequate and the examination shows no neoplasia, the ability to inspect the entire colon, and the ability to diagnose and treat lesions in the same session.
Screening colonoscopy visualizes the entire colon in more than 98% of cases, although it requires adequate bowel preparation for maximal polyp detection. It can be done safely with or without sedation.48
While there are no available randomized controlled trial data on the impact of screening colonoscopy on cancer incidence or mortality, extensive case-control and cohort studies consistently show that screening colonoscopy reduces cancer incidence and mortality rates.49–54 A US Veterans Administration study of more than 32,000 patients reported a 50% reduction in overall colorectal cancer mortality.55 In a microsimulation modeling study that assumed 100% adherence, colonoscopy every 10 years and annual FIT in individuals ages 50 to 75 provided similar life-years gained per 1,000 people screened (270 for colonoscopy, 244 for FIT).56
Well-established metrics for maximizing the effectiveness and quality of colonoscopy have been established (Table 2). The most important include the mucosa inspection time (withdrawal time) and adenoma detection rate.57 Withdrawal time is directly correlated with adenoma detection, and a 6-minute minimum withdrawal time is recommended in screening colonoscopy examinations of patients at average risk when no polyps are found.58 The adenoma detection rate is the strongest evidence-based metric, as each 1% increase in the adenoma detection rate over 19% is associated with a 3% decrease in the risk of colorectal cancer and a 5% decrease in death rate.59 The average-risk screening adenoma detection rate differs based on sex: the rate is greater than 20% for women and greater than 30% for men.
Complications from screening, diagnostic, or therapeutic colonoscopy are infrequent but include perforation (4/10,000) and significant intestinal bleeding (8/10,000).56–62
Patients with a first-degree relative under age 60 with advanced adenomas or colorectal cancer are considered at high risk and should begin screening colonoscopy at age 40, with repeat colonoscopy at 5-year intervals, given a trend toward advanced neoplasia detection compared with FIT.63
Guidelines recently published by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association also support starting screening in high-risk individuals at age 40, with a surveillance interval of 5 to 10 years based on the number of first-degree relatives with colorectal cancer or adenomas.64 Consensus statements were based on retrospective cohort, prospective case-controlled, and cross-sectional studies comparing the risk of colorectal cancer in individuals with a family history against those without a family history.
Randomized clinical trials comparing colonoscopy and FIT are under way. Interim analysis of a European trial in which asymptomatic adults ages 50 to 69 were randomized to 1-time colonoscopy (26,703 patients) vs FIT every 2 years (26,599 patients) found significantly higher participation rates in the FIT arm (34.2% vs 24.6%) but higher rates of nonadvanced adenomas (4.2% vs 0.4%) and advanced neoplasia (1.9% vs 0.9%) in the colonoscopy arm.65 Cancer was detected in 0.1% in each arm. These findings correlate with those of another study showing higher participation with FIT but higher advanced neoplasia detection rates with colonoscopy.66
Detection of precursor lesions is vital, as removing neoplasms is the main strategy to reduce colorectal cancer incidence. Accordingly, the advantage of colonoscopy was illustrated by a study that determined that 53 patients would need to undergo screening colonoscopy to detect 1 advanced adenoma or cancerous lesion, compared with 264 for FIT.67
STARTING SCREEING AT AGE 45
The American Cancer Society recently provided a qualified recommendation to start colorectal cancer screening in all individuals at age 45 rather than 50.9 This recommendation was based on modeling studies demonstrating that starting screening at age 45 with colonoscopy every 10 years resulted in 25 life-years gained at the cost of 610 colonoscopies per 1,000 individuals. Alternative strategies included FIT, which resulted in an additional 26 life-years gained per 1,000 individuals screened, flexible sigmoidoscopy (23 life-years gained), and computed tomographic colonoscopy (22 life-years gained).
Rates of colorectal cancer are rising in adults under age 50, and 10,000 new cases are anticipated this year.2,3 Currently, 22 million US adults are between the ages of 45 and 50. The system and support needed to perform screening in all adults over age 45 and a lack of direct evidence to support its benefits in the young population need to be considered before widespread acceptance of the American Cancer Society recommendations. However, if screening is considered, FIT with or without sigmoidoscopy may be appropriate, given that most cancers diagnosed in individuals under age 50 are left-sided.4,5
Screening has not been proven to reduce all-cause mortality. Randomized controlled trials of FOBT and observational studies of colonoscopy show that screening reduces cancer incidence and mortality. Until the currently ongoing randomized controlled trials comparing colonoscopy with FIT are completed, their comparative impact on colorectal cancer end points is unknown.
PATIENT ADHERENCE IS KEY
FIT and colonoscopy are the most prevalent screening methods in the United States. Careful attention should be given to offer the screening option the patient is most likely to complete, as adherence is key to the benefit from colorectal cancer screening.
The National Colorectal Cancer Roundtable (nccrt.org), established in 1997 by the American Cancer Society and the US Centers for Disease Control and Prevention, is a national coalition of public and private organizations dedicated to reducing colorectal cancer incidence and mortality. The Roundtable waged a national campaign to achieve a colorectal cancer screening rate of 80% in eligible adults by 2018, a goal that was not met. Still, the potential for a substantial impact is a compelling reason to endorse adherence to colorectal cancer screening. The Roundtable provides many resources for physicians to enhance screening in their practice.
The United States has seen a steady decline in colorectal cancer incidence and mortality, mainly as a result of screening. Colorectal cancer is preventable with ensuring patients’ adherence to screening. Screening rates have been shown to increase with patient-provider dialogue and with selection of a screening program the patient prefers and is most likely to complete.
Screening can help prevent colorectal cancer. The United States has seen a steady decline in colorectal cancer incidence and mortality, thanks in large part to screening. Screening rates can be increased with good patient-physician dialogue and by choosing a method the patient prefers and is most likely to complete.
In this article, we review a general approach to screening, focusing on the most commonly used methods in the United States, ie, the guaiac-based fecal occult blood test (FOBT), the fecal immunochemical test (FIT), and colonoscopy. We discuss current colorectal cancer incidence rates, screening recommendations, and how to choose the appropriate screening test.
This article does not discuss patients at high risk of polyps or cancer due to hereditary colon cancer syndromes, a personal history of colorectal neoplasia, inflammatory bowel disease, or primary sclerosing cholangitis.
TRENDS IN INCIDENCE
Colorectal cancer is the second most common type of cancer and cause of cancer-related deaths in the United States, responsible for an estimated 50,000 deaths in 2017. The lifetime risk of its occurrence is estimated to be 1 in 21 men and 1 in 23 women.1 Encouragingly, the incidence has declined by 24% over the last 30 years,2 and by 3% per year from 2004 to 2013.1 Also, as a result of screening and advances in treatment, 5-year survival rates for patients with colorectal cancer have increased, from 48.6% in 1975 to 66.4% in 2009.2
When detected at a localized stage, the 5-year survival rate in colorectal cancer is greater than 90%. Unfortunately, it is diagnosed early in only 39% of patients. And despite advances in treatment and a doubling of the 5-year survival rate in patients with advanced cancers since 1990,3 the latter is only 14%. In most patients, cancer is diagnosed when it has spread to the lymph nodes (36%) or to distant organs (22%), and the survival rate declines to 71% after lymph-node spread, and 14% after metastasis to distant organs.
It is essential to screen people who have no symptoms, as symptoms such as gastrointestinal bleeding, unexplained abdominal pain or weight loss, a persistent change in bowel movements, and bowel obstruction typically do not arise until the disease is advanced and less amenable to cure.
Increasing prevalence in younger adults
Curiously, the incidence of colorectal cancer is increasing in white US adults under age 50. Over the last 30 years, incidence rates have increased from 1.0% to 2.4% annually in adults ages 20 to 39.4 Based on current trends, colon cancer rates are expected to increase by 90% for patients ages 20 to 34 and by 28% for patients 35 to 49 by 2030.5
Although recommendations vary for colorectal cancer screening in patients under age 50, clinicians should investigate symptoms such as rectal bleeding, unexplained iron deficiency anemia, progressive abdominal pain, and persistent changes in bowel movements.
Other challenges
Despite the benefits of screening, it is underutilized. Although rates of compliance with screening recommendations have increased 10% over the last 10 years, only 65% of eligible adults currently comply.1,6
Additionally, certain areas of the country such as Appalachia and the Mississippi Delta have not benefited from the decline in the national rate of colorectal cancer.7
SCREENING GUIDELINES
Most guidelines say that colorectal cancer screening should begin at age 50 in people at average risk with no symptoms. However, the American College of Gastroenterology (ACG) recommends beginning screening at age 45 in African Americans, as this group has higher incidence and mortality rates of colorectal cancer.8 Also, the American Cancer Society recently recommended beginning screening at age 45 for all individuals.9
Screening can stop at age 75 for most patients, according to the ACG,8 the US Multi-Society Task Force on Colorectal Cancer,10 and the US Preventive Services Task Force (USPSTF).11 However, the decision should be individualized for patients ages 76 to 85. Patients within that age group who are in good health and have not previously been screened are more likely to benefit than those who have previously been screened and had a negative screening test. Patients over age 85 should not begin or continue screening, because of diminished benefit of screening in this age group, shorter life expectancy, advanced comorbid conditions, and the risks of colonoscopy and cancer treatment.
Patients and clinicians are encouraged to collaborate in deciding which screening method is appropriate. Patients adhere better when they are given a choice in the matter.12–14 And adherence is the key to effective colorectal cancer screening.
Familiarity with the key characteristics of currently available colorectal cancer screening tests will facilitate discussion with patients.
Opportunistic vs programmatic screening
Screening can be classified according to the approach to the patient or population and the intent of the test. Most screening in the United States is opportunistic rather than programmatic—that is, the physician offers the patient screening at the point of service without systematic follow-up or patient re-engagement.
In a programmatic approach, the patient is offered screening through an organized program that streamlines services, reduces overscreening, and provides systematic follow-up of testing.
DISCUSSING THE OPTIONS
Stool studies such as FOBT and FIT do not reliably detect cancer precursors such as adenomas and serrated neoplasms. If an FOBT is positive, follow-up diagnostic colonoscopy is required. Unlike screening colonoscopy, diagnostic colonoscopy requires a copayment for Medicare patients, and this should be explained to the patient.
FIT and FOBT detect hemolyzed blood within a stool sample, FOBT by a chemical reaction, and FIT by detecting a globin-specific antibody. Colorectal cancer and some large adenomatous polyps may intermittently bleed and result in occult blood in the stool, iron deficiency anemia, or hematochezia.15
Fecal occult blood testing
Historically, FOBT was the stool test of choice for screening. It uses an indirect enzymatic reaction to detect hemolyzed blood in the stool. When a specimen containing hemoglobin is added to guaiac paper and a drop of hydrogen peroxide is added to “develop” it, the peroxidase activity of hemoglobin turns the guaiac blue.
Screening with FOBT involves annual testing of 3 consecutively passed stools from different days; FOBT should not be performed at the time of digital rectal examination or if the patient is having overt rectal, urinary, or menstrual bleeding.
Dietary and medication restrictions before and during the testing period are critical, as red meat contains hemoglobin, and certain vegetables (eg, radishes, turnips, cauliflower, cucumbers) contain peroxidase, all of which can cause a false-positive result. Waiting 3 days after the stool sample is collected to develop it can mitigate the peroxidase activity of vegetables.16 Vitamin C inhibits heme peroxidase activity and leads to false-negative results. Aspirin and high-dose nonsteroidal anti-inflammatory drugs can promote bleeding throughout the intestinal tract.17
In randomized controlled trials,18–21 screening with FOBT reduced colorectal cancer mortality rates by 15% to 33%. The 30-year follow-up of a large US trial22 found a 32% relative reduction in mortality rates in patients randomized to annual screening, and a 22% relative reduction in those randomized to screening every 2 years. Despite the many possibilities for false-positive results, the specificity for detecting cancer has ranged from 86.7% to 97.3%, and the sensitivity from 37.1% to 79.4%, highlighting the benefit of colorectal cancer screening programs in unscreened populations.23–26
FIT vs FOBT in current practice
FIT should replace FOBT as the preferred stool screening method. Instead of an enzymatic reaction that can be altered by food or medication, FIT utilizes an antibody specific to human globin to directly detect hemolyzed blood, thus eliminating the need to modify the diet or medications.27 Additionally, only 1 stool specimen is needed, which may explain why the adherence rate was about 20% higher with FIT than with FOBT in most studies.28–30
FIT has a sensitivity of 69% to 86% for colorectal cancer and a specificity of 92% to 95%.31 The sensitivity can be improved by lowering the threshold value for a positive test, but this is associated with a decrease in specificity. A single FIT has the same sensitivity and specificity as several samples.32
In a large retrospective US cohort study of programmatic screening with FIT, Jensen et al33 reported that 48% of 670,841 people who were offered testing actually did the test. Of the 48% who participated in the first round and remained eligible, 75% to 86% participated in subsequent rounds over 4 years. Those who had a positive result on FIT were supposed to undergo colonoscopy, but 22% did not.
The US Multi-Society Task Force on Colorectal Cancer34 suggests that FIT-based screening programs aim for a target FIT completion rate of more than 60% and a target colonoscopy completion rate of more than 80% of patients with positive FITs. These benchmarks were derived from adherence rates in international FIT screening studies in average-risk populations.35–39 (Note that the large US cohort described above33 did not meet these goals.) Ideally, every patient with a positive FIT should undergo diagnostic colonoscopy, but in reality only 50% to 83% actually do. Methods shown to improve adherence include structured screening programs with routine performance reports, provider feedback, and involvement of patient navigators.40–42
Accordingly, several aspects of stool-based testing need to be stressed with patients. Understanding that FOBT is recommended yearly is integral for optimal impact on colorectal cancer incidence and mortality rates.
Additionally, patients should be advised to undergo colonoscopy soon after a positive FIT, because delaying colonoscopy could give precancerous lesions time to progress in stage. The acceptable time between a positive FIT and colonoscopy has yet to be determined. However, a retrospective cohort study of 1.26 million screened patients with 107,000 positive FIT results demonstrated that the rates of cancer discovered on colonoscopy were similar when performed within 30 days or up to 10 months after a positive test. Detection rates increased from 3% to 4.8% at 10 months and to 7.9% at 12 months.43
In modeling studies, Meester et al44 showed the estimated lifetime risk and mortality rates from colorectal cancer and life-years gained from screening are significantly better when colonoscopy is completed within 2 weeks rather than 1 year after a positive FIT. Each additional month after 2 weeks incrementally affected these outcomes, with a 1.4% increase in cancer mortality. These data suggest that colonoscopy should be done soon after a positive FIT result and at a maximum of 10 months.43,44
Screening with FOBT is a multistep process for patients that includes receiving the test kit, collecting the sample, preparing it, returning it, undergoing colonoscopy after a positive test, and repeating in 1 year if negative. The screening program should identify patients at average risk in whom screening is appropriate, ensure delivery of the test, verify the quality of collected samples for laboratory testing against the manufacturer’s recommendations, and report results. Report of a positive FOBT result should provide recommendations for follow-up.
Though evidence clearly supports screening annually or biennially (every 2 years) with FOBT, the ideal interval for FIT is undetermined. Modeling studies utilized by the USPSTF and Multi-Society Task Force demonstrate that colonoscopy and annual FIT result in similar life-years gained, while 2 population-based screening programs have demonstrated that a 2- or 3-year interval may be equally efficacious by lowering the threshold for a positive test.38,45
Randomized controlled trials of screening colonoscopy vs annual and biennial FIT are currently under way. Cost-effectiveness analysis has shown that offering single-sample FITs at more frequent (annual) intervals performs better than multisample testing at less frequent intervals.45–47
Colonoscopy
Compared with stool-based screening, colonoscopy has advantages, including a 10-year screening interval if bowel preparation is adequate and the examination shows no neoplasia, the ability to inspect the entire colon, and the ability to diagnose and treat lesions in the same session.
Screening colonoscopy visualizes the entire colon in more than 98% of cases, although it requires adequate bowel preparation for maximal polyp detection. It can be done safely with or without sedation.48
While there are no available randomized controlled trial data on the impact of screening colonoscopy on cancer incidence or mortality, extensive case-control and cohort studies consistently show that screening colonoscopy reduces cancer incidence and mortality rates.49–54 A US Veterans Administration study of more than 32,000 patients reported a 50% reduction in overall colorectal cancer mortality.55 In a microsimulation modeling study that assumed 100% adherence, colonoscopy every 10 years and annual FIT in individuals ages 50 to 75 provided similar life-years gained per 1,000 people screened (270 for colonoscopy, 244 for FIT).56
Well-established metrics for maximizing the effectiveness and quality of colonoscopy have been established (Table 2). The most important include the mucosa inspection time (withdrawal time) and adenoma detection rate.57 Withdrawal time is directly correlated with adenoma detection, and a 6-minute minimum withdrawal time is recommended in screening colonoscopy examinations of patients at average risk when no polyps are found.58 The adenoma detection rate is the strongest evidence-based metric, as each 1% increase in the adenoma detection rate over 19% is associated with a 3% decrease in the risk of colorectal cancer and a 5% decrease in death rate.59 The average-risk screening adenoma detection rate differs based on sex: the rate is greater than 20% for women and greater than 30% for men.
Complications from screening, diagnostic, or therapeutic colonoscopy are infrequent but include perforation (4/10,000) and significant intestinal bleeding (8/10,000).56–62
Patients with a first-degree relative under age 60 with advanced adenomas or colorectal cancer are considered at high risk and should begin screening colonoscopy at age 40, with repeat colonoscopy at 5-year intervals, given a trend toward advanced neoplasia detection compared with FIT.63
Guidelines recently published by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association also support starting screening in high-risk individuals at age 40, with a surveillance interval of 5 to 10 years based on the number of first-degree relatives with colorectal cancer or adenomas.64 Consensus statements were based on retrospective cohort, prospective case-controlled, and cross-sectional studies comparing the risk of colorectal cancer in individuals with a family history against those without a family history.
Randomized clinical trials comparing colonoscopy and FIT are under way. Interim analysis of a European trial in which asymptomatic adults ages 50 to 69 were randomized to 1-time colonoscopy (26,703 patients) vs FIT every 2 years (26,599 patients) found significantly higher participation rates in the FIT arm (34.2% vs 24.6%) but higher rates of nonadvanced adenomas (4.2% vs 0.4%) and advanced neoplasia (1.9% vs 0.9%) in the colonoscopy arm.65 Cancer was detected in 0.1% in each arm. These findings correlate with those of another study showing higher participation with FIT but higher advanced neoplasia detection rates with colonoscopy.66
Detection of precursor lesions is vital, as removing neoplasms is the main strategy to reduce colorectal cancer incidence. Accordingly, the advantage of colonoscopy was illustrated by a study that determined that 53 patients would need to undergo screening colonoscopy to detect 1 advanced adenoma or cancerous lesion, compared with 264 for FIT.67
STARTING SCREEING AT AGE 45
The American Cancer Society recently provided a qualified recommendation to start colorectal cancer screening in all individuals at age 45 rather than 50.9 This recommendation was based on modeling studies demonstrating that starting screening at age 45 with colonoscopy every 10 years resulted in 25 life-years gained at the cost of 610 colonoscopies per 1,000 individuals. Alternative strategies included FIT, which resulted in an additional 26 life-years gained per 1,000 individuals screened, flexible sigmoidoscopy (23 life-years gained), and computed tomographic colonoscopy (22 life-years gained).
Rates of colorectal cancer are rising in adults under age 50, and 10,000 new cases are anticipated this year.2,3 Currently, 22 million US adults are between the ages of 45 and 50. The system and support needed to perform screening in all adults over age 45 and a lack of direct evidence to support its benefits in the young population need to be considered before widespread acceptance of the American Cancer Society recommendations. However, if screening is considered, FIT with or without sigmoidoscopy may be appropriate, given that most cancers diagnosed in individuals under age 50 are left-sided.4,5
Screening has not been proven to reduce all-cause mortality. Randomized controlled trials of FOBT and observational studies of colonoscopy show that screening reduces cancer incidence and mortality. Until the currently ongoing randomized controlled trials comparing colonoscopy with FIT are completed, their comparative impact on colorectal cancer end points is unknown.
PATIENT ADHERENCE IS KEY
FIT and colonoscopy are the most prevalent screening methods in the United States. Careful attention should be given to offer the screening option the patient is most likely to complete, as adherence is key to the benefit from colorectal cancer screening.
The National Colorectal Cancer Roundtable (nccrt.org), established in 1997 by the American Cancer Society and the US Centers for Disease Control and Prevention, is a national coalition of public and private organizations dedicated to reducing colorectal cancer incidence and mortality. The Roundtable waged a national campaign to achieve a colorectal cancer screening rate of 80% in eligible adults by 2018, a goal that was not met. Still, the potential for a substantial impact is a compelling reason to endorse adherence to colorectal cancer screening. The Roundtable provides many resources for physicians to enhance screening in their practice.
The United States has seen a steady decline in colorectal cancer incidence and mortality, mainly as a result of screening. Colorectal cancer is preventable with ensuring patients’ adherence to screening. Screening rates have been shown to increase with patient-provider dialogue and with selection of a screening program the patient prefers and is most likely to complete.
- American Cancer Society. Colorectal Cancer Facts & Figures 2017–2019. Atlanta: American Cancer Society; 2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2017-2019.pdf. Accessed April 1, 2019.
- Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin 2017; 67(3):177–193. doi:10.3322/caac.21395
- Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 2009; 27(22):3677–3683. doi:10.1200/JCO.2008.20.5278
- Siegel RL, Jemal A, Ward EM. Increase in incidence of colorectal cancer among young men and women in the United States. Cancer Epidemiol Biomarkers Prev 2009; 18(6):1695–1698. doi:10.1158/1055-9965.EPI-09-0186
- Bailey CE, Hu CY, You YN, et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg 2015; 150(1):17–22. doi:10.1001/jamasurg.2014.1756
- Centers for Disease Control and Prevention (CDC). Vital signs: colorectal cancer screening test use—United States, 2012. MMWR Morb Mortal Wkly Rep 2013; 62(44):881–888. pmid:24196665
- Siegel RL, Sahar L, Robbins A, Jemal A. Where can colorectal cancer screening interventions have the most impact? Cancer Epidemiol Biomarkers Prev 2015; 24(8):1151–1156. doi:10.1158/1055-9965.EPI-15-0082
- Agrawal S, Bhupinderjit A, Bhutani MS, et al; Committee of Minority Affairs and Cultural Diversity, American College of Gastroenterology. Colorectal cancer in African Americans. Am J Gastroenterol 2005; 100(3):515–523. doi:10.1111/j.1572-0241.2005.41829.x
- Wolf AMD, Fontham ETH, Church TR, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin 2018; 68(4):250–281. doi:10.3322/caac.21457
- Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: recommendations for physicians and patients from the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2017; 112(7):1016–1030. doi:10.1038/ajg.2017.174
- US Preventive Services Task Force; Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for colorectal cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2016; 315(23):2564–2575. doi:10.1001/jama.2016.5989
- Inadomi JM, Vijan S, Janz NK, et al. Adherence to colorectal cancer screening: a randomized clinical trial of competing strategies. Arch Intern Med 2012; 172(7):575–582. doi:10.1001/archinternmed.2012.332
- Steinwachs D, Allen JD, Barlow WE, et al. National Institutes of Health state-of-the-science conference statement: enhancing use and quality of colorectal cancer screening. Ann Intern Med 2010; 152(10):663–667. doi:10.7326/0003-4819-152-10-201005180-00237
- Subramanian S, Klosterman M, Amonkar MM, Hunt TL. Adherence with colorectal cancer screening guidelines: a review. Prev Med 2004; 38(5):536–550. doi:10.1016/j.ypmed.2003.12.011
- Levin B, Lieberman DA, McFarland B, et al; American Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin 2008; 58(3):130–160. doi:10.3322/CA.2007.0018
- Sinatra MA, St John DJ, Young GP. Interference of plant peroxidases with guaiac-based fecal occult blood tests is avoidable. Clin Chem 1999; 45(1):123–126. pmid:9895348
- Allison JE, Sakoda LC, Levin TR, et al. Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst 2007; 99(19):1462–1470. doi:10.1093/jnci/djm150
- Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328(19):1365–1371. doi:10.1056/NEJM199305133281901
- Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348(9040):1472–1477. doi:10.1016/S0140-6736(96)03386-7
- Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996; 348(9040):1467–1471. doi:10.1016/S0140-6736(96)03430-7
- Wilson JMG, Junger G. Principles and practice of screening for disease. Geneva, Switzerland: World Health Organization; 1968. http://apps.who.int/iris/bitstream/handle/10665/37650/WHO_PHP_34.pdf?sequence=17. Accessed April 1, 2019.
- Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med 2013; 369(12):1106–1114. doi:10.1056/NEJMoa1300720
- Allison JE, Tekawa IS, Ransom LJ, Adrain AL. A comparison of fecal occult-blood tests for colorectal-cancer screening. N Engl J Med 1996; 334(3):155–159. doi:10.1056/NEJM199601183340304
- Shapiro JA, Bobo JK, Church TR, et al. A comparison of fecal immunochemical and high-sensitivity guaiac tests for colorectal cancer screening. Am J Gastroenterol 2017; 112(11):1728–1735. doi:10.1038/ajg.2017.285
- Smith A, Young GP, Cole SR, Bampton P. Comparison of a brush-sampling fecal immunochemical test for hemoglobin with a sensitive guaiac-based fecal occult blood test in detection of colorectal neoplasia. Cancer 2006; 107(9):2152–2159. doi:10.1002/cncr.22230
- Brenner H, Tao S. Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy. Eur J Cancer 2013; 49(14):3049–3054. doi:10.1016/j.ejca.2013.04.023
- Young GP, Cole S. New stool screening tests for colorectal cancer. Digestion 2007; 76(1):26–33. doi:10.1159/000108391
- van Rossum LG, van Rijn AF, Laheij RJ, et al. Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population. Gastroenterology 2008; 135(1):82–90. doi:10.1053/j.gastro.2008.03.040
- Hassan C, Giorgi Rossi P, Camilloni L, et al. Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test. Aliment Pharmacol Ther 2012; 36(10):929–940. doi:10.1111/apt.12071
- Vart G, Banzi R, Minozzi S. Comparing participation rates between immunochemical and guaiac faecal occult blood tests: a systematic review and meta-analysis. Prev Med 2012; 55(2):87–92. doi:10.1016/j.ypmed.2012.05.006
- Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med 2014; 370(14):1287–1297. doi:10.1056/NEJMoa1311194
- Lee JK, Liles EG, Bent S, Levin TR, Corley DA. Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis. Ann Intern Med 2014; 160(3):171. doi:10.7326/M13-1484
- Jensen CD, Corley DA, Quinn VP, et al. Fecal immunochemical test program performance over 4 rounds of annual screening: a retrospective cohort study. Ann Intern Med 2016; 164(7):456–463. doi:10.7326/M15-0983
- Robertson DJ, Lee JK, Boland CR, et al. Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2017; 152(5):1217–1237.e3. doi:10.1053/j.gastro.2016.08.053
- Rabeneck L, Rumble RB, Thompson F, et al. Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening. Can J Gastroenterol 2012; 26(3):131–147. pmid:22408764
- Logan RF, Patnick J, Nickerson C, Coleman L, Rutter MD, von Wagner C; English Bowel Cancer Screening Evaluation Committee. Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests. Gut 2012; 61(10):1439–1446. doi:10.1136/gutjnl-2011-300843
- Malila N, Oivanen T, Malminiemi O, Hakama M. Test, episode, and programme sensitivities of screening for colorectal cancer as a public health policy in Finland: experimental design. BMJ 2008; 337:a2261. doi:10.1136/bmj.a2261
- Denters MJ, Deutekom M, Bossuyt PM, Stroobants AK, Fockens P, Dekker E. Lower risk of advanced neoplasia among patients with a previous negative result from a fecal test for colorectal cancer. Gastroenterology 2012; 142(3):497–504. doi:10.1053/j.gastro.2011.11.024
- van Roon AH, Goede SL, van Ballegooijen M, et al. Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening. Gut 2013; 62(3):409–415. doi:10.1136/gutjnl-2011-301583
- Chubak J, Garcia MP, Burnett-Hartman AN, et al; PROSPR consortium. Time to colonoscopy after positive fecal blood test in four US health care systems. Cancer Epidemiol Biomarkers Prev 2016; 25(2):344–350. doi:10.1158/1055-9965.EPI-15-0470
- Carlson CM, Kirby KA, Casadei MA, Partin MR, Kistler CE, Walter LC. Lack of follow-up after fecal occult blood testing in older adults: inappropriate screening or failure to follow up? Arch Intern Med 2011; 171(3):249–256. doi:10.1001/archinternmed.2010.372
- Selby K, Baumgartner C, Levin TR, et al. Interventions to improve follow-up of positive results on fecal blood tests: a systematic review. Ann Intern Med 2017; 167(8):565–575. doi:10.7326/M17-1361
- Corley DA, Jensen CD, Quinn VP, et al. Association between time to colonoscopy after a positive fecal test result and risk of colorectal cancer and cancer stage at diagnosis. JAMA 2017; 317(16):1631–1641. doi:10.1001/jama.2017.3634
- Meester RG, Zauber AG, Doubeni CA, et al. Consequences of increasing time to colonoscopy examination after positive result from fecal colorectal cancer screening test. Clin Gastroenterol Hepatol 2016; 14(10):1445–1451.e8. doi:10.1016/j.cgh.2016.05.017
- Haug U, Grobbee EJ, Lansdorp-Vogelaar I, Spaander MCW, Kuipers EJ. Immunochemical faecal occult blood testing to screen for colorectal cancer: can the screening interval be extended? Gut 2017; 66(7):1262–1267. doi:10.1136/gutjnl-2015-310102
- Goede SL, van Roon AH, Reijerink JC, et al. Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening. Gut 2013; 62(5):727–734. doi:10.1136/gutjnl-2011-301917
- Digby J, Fraser CG, Carey FA, Steele RJC. Can the performance of a quantitative FIT-based colorectal cancer screening programme be enhanced by lowering the threshold and increasing the interval? Gut 2018; 67(5):993–994. doi:10.1136/gutjnl-2017-314862
- Hoffman MS, Butler TW, Shaver T. Colonoscopy without sedation. J Clin Gastroenterol 1998; 26(4):279–282. pmid:9649011
- Zauber AG, Winawer SJ, O’Brien MJ, et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 2012; 366(8):687–696. doi:10.1056/NEJMoa1100370
- Nishihara R, Wu K, Lochhead P, et al. Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 2013; 369(12):1095–1105. doi:10.1056/NEJMoa1301969
- Løberg M, Kalager M, Holme Ø, Hoff G, Adami HO, Bretthauer M. Long-term colorectal-cancer mortality after adenoma removal. N Engl J Med 2014; 371(9):799–807. doi:10.1056/NEJMoa1315870
- Manser CN, Bachmann LM, Brunner J, Hunold F, Bauerfeind P, Marbet UA. Colonoscopy screening markedly reduces the occurrence of colon carcinomas and carcinoma-related death: a closed cohort study. Gastrointest Endosc 2012; 76(1):110–117. doi:10.1016/j.gie.2012.02.040
- Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993; 329(27):1977–1981. doi:10.1056/NEJM199312303292701
- Citarda F, Tomaselli G, Capocaccia R, Barcherini S, Crespi M; Italian Multicentre Study Group. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence. Gut 2001; 48(6):812–815. pmid:11358901
- Muller AD, Sonnenberg A. Prevention of colorectal cancer by flexible endoscopy and polypectomy. A case-control study of 32,702 veterans. Ann Intern Med 1995; 123(12):904–910. pmid:7486484
- Knudsen AB, Zauber AG, Rutter CM, et al. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA 2016; 315(23):2595–2609. doi:10.1001/jama.2016.6828
- Rex DK, Schoenfeld PS, Cohen J, et al. Quality indicators for colonoscopy. Gastrointest Endosc 2015; 81(1):31–53. doi:10.1016/j.gie.2014.07.058
- Barclay RL, Vicari JJ, Doughty AS, Johanson JF, Greenlaw RL. Colonoscopic withdrawal times and adenoma detection during screening colonoscopy. N Engl J Med 2006; 355(24):2533–2541. doi:10.1056/NEJMoa055498
- Corley DA, Levin TR, Doubeni CA. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med 2014; 370(26):2541. doi:10.1056/NEJMc1405329
- Lin JS, Piper MA, Perdue LA, et al. Screening for colorectal cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016; 315(23):2576–2594. doi:10.1001/jama.2016.3332
- Gatto NM, Frucht H, Sundararajan V, Jacobson JS, Grann VR, Neugut AI. Risk of perforation after colonoscopy and sigmoidoscopy: a population-based study. J Natl Cancer Inst 2003; 95(3):230–236. pmid:12569145
- Warren JL, Klabunde CN, Mariotto AB, et al. Adverse events after outpatient colonoscopy in the Medicare population. Ann Intern Med 2009; 150(12):849–857, W152. pmid:19528563
- Quintero E, Carrillo M, Gimeno-García AZ, et al. Equivalency of fecal immunochemical tests and colonoscopy in familial colorectal cancer screening. Gastroenterology 2014; 147(5):1021–130.e1. doi:10.1053/j.gastro.2014.08.004
- Leddin D, Lieberman DA, Tse F, et al. Clinical practice guideline on screening for colorectal cancer in individuals with a family history of nonhereditary colorectal cancer or adenoma: the Canadian Association of Gastroenterology Banff Consensus. Gastroenterology 2018; 155(5):1325–1347.e3. doi:10.1053/j.gastro.2018.08.017
- Quintero E, Castells A, Bujanda L, et al; COLONPREV Study Investigators. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med 2012; 366(8):697–706. doi:10.1056/NEJMoa1108895
- Gupta S, Halm EA, Rockey DC, et al. Comparative effectiveness of fecal immunochemical test outreach, colonoscopy outreach, and usual care for boosting colorectal cancer screening among the underserved: a randomized clinical trial. JAMA Intern Med 2013; 173(18):1725–1732. doi:10.1001/jamainternmed.2013.9294
- Segnan N, Senore C, Andreoni B, et al; SCORE3 Working Group-Italy. Comparing attendance and detection rate of colonoscopy with sigmoidoscopy and FIT for colorectal cancer screening. Gastroenterology 2007; 132(7):2304–2312. doi:10.1053/j.gastro.2007.03.030
- American Cancer Society. Colorectal Cancer Facts & Figures 2017–2019. Atlanta: American Cancer Society; 2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2017-2019.pdf. Accessed April 1, 2019.
- Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin 2017; 67(3):177–193. doi:10.3322/caac.21395
- Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 2009; 27(22):3677–3683. doi:10.1200/JCO.2008.20.5278
- Siegel RL, Jemal A, Ward EM. Increase in incidence of colorectal cancer among young men and women in the United States. Cancer Epidemiol Biomarkers Prev 2009; 18(6):1695–1698. doi:10.1158/1055-9965.EPI-09-0186
- Bailey CE, Hu CY, You YN, et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg 2015; 150(1):17–22. doi:10.1001/jamasurg.2014.1756
- Centers for Disease Control and Prevention (CDC). Vital signs: colorectal cancer screening test use—United States, 2012. MMWR Morb Mortal Wkly Rep 2013; 62(44):881–888. pmid:24196665
- Siegel RL, Sahar L, Robbins A, Jemal A. Where can colorectal cancer screening interventions have the most impact? Cancer Epidemiol Biomarkers Prev 2015; 24(8):1151–1156. doi:10.1158/1055-9965.EPI-15-0082
- Agrawal S, Bhupinderjit A, Bhutani MS, et al; Committee of Minority Affairs and Cultural Diversity, American College of Gastroenterology. Colorectal cancer in African Americans. Am J Gastroenterol 2005; 100(3):515–523. doi:10.1111/j.1572-0241.2005.41829.x
- Wolf AMD, Fontham ETH, Church TR, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin 2018; 68(4):250–281. doi:10.3322/caac.21457
- Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: recommendations for physicians and patients from the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2017; 112(7):1016–1030. doi:10.1038/ajg.2017.174
- US Preventive Services Task Force; Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for colorectal cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2016; 315(23):2564–2575. doi:10.1001/jama.2016.5989
- Inadomi JM, Vijan S, Janz NK, et al. Adherence to colorectal cancer screening: a randomized clinical trial of competing strategies. Arch Intern Med 2012; 172(7):575–582. doi:10.1001/archinternmed.2012.332
- Steinwachs D, Allen JD, Barlow WE, et al. National Institutes of Health state-of-the-science conference statement: enhancing use and quality of colorectal cancer screening. Ann Intern Med 2010; 152(10):663–667. doi:10.7326/0003-4819-152-10-201005180-00237
- Subramanian S, Klosterman M, Amonkar MM, Hunt TL. Adherence with colorectal cancer screening guidelines: a review. Prev Med 2004; 38(5):536–550. doi:10.1016/j.ypmed.2003.12.011
- Levin B, Lieberman DA, McFarland B, et al; American Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin 2008; 58(3):130–160. doi:10.3322/CA.2007.0018
- Sinatra MA, St John DJ, Young GP. Interference of plant peroxidases with guaiac-based fecal occult blood tests is avoidable. Clin Chem 1999; 45(1):123–126. pmid:9895348
- Allison JE, Sakoda LC, Levin TR, et al. Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst 2007; 99(19):1462–1470. doi:10.1093/jnci/djm150
- Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328(19):1365–1371. doi:10.1056/NEJM199305133281901
- Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348(9040):1472–1477. doi:10.1016/S0140-6736(96)03386-7
- Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996; 348(9040):1467–1471. doi:10.1016/S0140-6736(96)03430-7
- Wilson JMG, Junger G. Principles and practice of screening for disease. Geneva, Switzerland: World Health Organization; 1968. http://apps.who.int/iris/bitstream/handle/10665/37650/WHO_PHP_34.pdf?sequence=17. Accessed April 1, 2019.
- Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med 2013; 369(12):1106–1114. doi:10.1056/NEJMoa1300720
- Allison JE, Tekawa IS, Ransom LJ, Adrain AL. A comparison of fecal occult-blood tests for colorectal-cancer screening. N Engl J Med 1996; 334(3):155–159. doi:10.1056/NEJM199601183340304
- Shapiro JA, Bobo JK, Church TR, et al. A comparison of fecal immunochemical and high-sensitivity guaiac tests for colorectal cancer screening. Am J Gastroenterol 2017; 112(11):1728–1735. doi:10.1038/ajg.2017.285
- Smith A, Young GP, Cole SR, Bampton P. Comparison of a brush-sampling fecal immunochemical test for hemoglobin with a sensitive guaiac-based fecal occult blood test in detection of colorectal neoplasia. Cancer 2006; 107(9):2152–2159. doi:10.1002/cncr.22230
- Brenner H, Tao S. Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy. Eur J Cancer 2013; 49(14):3049–3054. doi:10.1016/j.ejca.2013.04.023
- Young GP, Cole S. New stool screening tests for colorectal cancer. Digestion 2007; 76(1):26–33. doi:10.1159/000108391
- van Rossum LG, van Rijn AF, Laheij RJ, et al. Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population. Gastroenterology 2008; 135(1):82–90. doi:10.1053/j.gastro.2008.03.040
- Hassan C, Giorgi Rossi P, Camilloni L, et al. Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test. Aliment Pharmacol Ther 2012; 36(10):929–940. doi:10.1111/apt.12071
- Vart G, Banzi R, Minozzi S. Comparing participation rates between immunochemical and guaiac faecal occult blood tests: a systematic review and meta-analysis. Prev Med 2012; 55(2):87–92. doi:10.1016/j.ypmed.2012.05.006
- Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med 2014; 370(14):1287–1297. doi:10.1056/NEJMoa1311194
- Lee JK, Liles EG, Bent S, Levin TR, Corley DA. Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis. Ann Intern Med 2014; 160(3):171. doi:10.7326/M13-1484
- Jensen CD, Corley DA, Quinn VP, et al. Fecal immunochemical test program performance over 4 rounds of annual screening: a retrospective cohort study. Ann Intern Med 2016; 164(7):456–463. doi:10.7326/M15-0983
- Robertson DJ, Lee JK, Boland CR, et al. Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2017; 152(5):1217–1237.e3. doi:10.1053/j.gastro.2016.08.053
- Rabeneck L, Rumble RB, Thompson F, et al. Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening. Can J Gastroenterol 2012; 26(3):131–147. pmid:22408764
- Logan RF, Patnick J, Nickerson C, Coleman L, Rutter MD, von Wagner C; English Bowel Cancer Screening Evaluation Committee. Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests. Gut 2012; 61(10):1439–1446. doi:10.1136/gutjnl-2011-300843
- Malila N, Oivanen T, Malminiemi O, Hakama M. Test, episode, and programme sensitivities of screening for colorectal cancer as a public health policy in Finland: experimental design. BMJ 2008; 337:a2261. doi:10.1136/bmj.a2261
- Denters MJ, Deutekom M, Bossuyt PM, Stroobants AK, Fockens P, Dekker E. Lower risk of advanced neoplasia among patients with a previous negative result from a fecal test for colorectal cancer. Gastroenterology 2012; 142(3):497–504. doi:10.1053/j.gastro.2011.11.024
- van Roon AH, Goede SL, van Ballegooijen M, et al. Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening. Gut 2013; 62(3):409–415. doi:10.1136/gutjnl-2011-301583
- Chubak J, Garcia MP, Burnett-Hartman AN, et al; PROSPR consortium. Time to colonoscopy after positive fecal blood test in four US health care systems. Cancer Epidemiol Biomarkers Prev 2016; 25(2):344–350. doi:10.1158/1055-9965.EPI-15-0470
- Carlson CM, Kirby KA, Casadei MA, Partin MR, Kistler CE, Walter LC. Lack of follow-up after fecal occult blood testing in older adults: inappropriate screening or failure to follow up? Arch Intern Med 2011; 171(3):249–256. doi:10.1001/archinternmed.2010.372
- Selby K, Baumgartner C, Levin TR, et al. Interventions to improve follow-up of positive results on fecal blood tests: a systematic review. Ann Intern Med 2017; 167(8):565–575. doi:10.7326/M17-1361
- Corley DA, Jensen CD, Quinn VP, et al. Association between time to colonoscopy after a positive fecal test result and risk of colorectal cancer and cancer stage at diagnosis. JAMA 2017; 317(16):1631–1641. doi:10.1001/jama.2017.3634
- Meester RG, Zauber AG, Doubeni CA, et al. Consequences of increasing time to colonoscopy examination after positive result from fecal colorectal cancer screening test. Clin Gastroenterol Hepatol 2016; 14(10):1445–1451.e8. doi:10.1016/j.cgh.2016.05.017
- Haug U, Grobbee EJ, Lansdorp-Vogelaar I, Spaander MCW, Kuipers EJ. Immunochemical faecal occult blood testing to screen for colorectal cancer: can the screening interval be extended? Gut 2017; 66(7):1262–1267. doi:10.1136/gutjnl-2015-310102
- Goede SL, van Roon AH, Reijerink JC, et al. Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening. Gut 2013; 62(5):727–734. doi:10.1136/gutjnl-2011-301917
- Digby J, Fraser CG, Carey FA, Steele RJC. Can the performance of a quantitative FIT-based colorectal cancer screening programme be enhanced by lowering the threshold and increasing the interval? Gut 2018; 67(5):993–994. doi:10.1136/gutjnl-2017-314862
- Hoffman MS, Butler TW, Shaver T. Colonoscopy without sedation. J Clin Gastroenterol 1998; 26(4):279–282. pmid:9649011
- Zauber AG, Winawer SJ, O’Brien MJ, et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 2012; 366(8):687–696. doi:10.1056/NEJMoa1100370
- Nishihara R, Wu K, Lochhead P, et al. Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 2013; 369(12):1095–1105. doi:10.1056/NEJMoa1301969
- Løberg M, Kalager M, Holme Ø, Hoff G, Adami HO, Bretthauer M. Long-term colorectal-cancer mortality after adenoma removal. N Engl J Med 2014; 371(9):799–807. doi:10.1056/NEJMoa1315870
- Manser CN, Bachmann LM, Brunner J, Hunold F, Bauerfeind P, Marbet UA. Colonoscopy screening markedly reduces the occurrence of colon carcinomas and carcinoma-related death: a closed cohort study. Gastrointest Endosc 2012; 76(1):110–117. doi:10.1016/j.gie.2012.02.040
- Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993; 329(27):1977–1981. doi:10.1056/NEJM199312303292701
- Citarda F, Tomaselli G, Capocaccia R, Barcherini S, Crespi M; Italian Multicentre Study Group. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence. Gut 2001; 48(6):812–815. pmid:11358901
- Muller AD, Sonnenberg A. Prevention of colorectal cancer by flexible endoscopy and polypectomy. A case-control study of 32,702 veterans. Ann Intern Med 1995; 123(12):904–910. pmid:7486484
- Knudsen AB, Zauber AG, Rutter CM, et al. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA 2016; 315(23):2595–2609. doi:10.1001/jama.2016.6828
- Rex DK, Schoenfeld PS, Cohen J, et al. Quality indicators for colonoscopy. Gastrointest Endosc 2015; 81(1):31–53. doi:10.1016/j.gie.2014.07.058
- Barclay RL, Vicari JJ, Doughty AS, Johanson JF, Greenlaw RL. Colonoscopic withdrawal times and adenoma detection during screening colonoscopy. N Engl J Med 2006; 355(24):2533–2541. doi:10.1056/NEJMoa055498
- Corley DA, Levin TR, Doubeni CA. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med 2014; 370(26):2541. doi:10.1056/NEJMc1405329
- Lin JS, Piper MA, Perdue LA, et al. Screening for colorectal cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016; 315(23):2576–2594. doi:10.1001/jama.2016.3332
- Gatto NM, Frucht H, Sundararajan V, Jacobson JS, Grann VR, Neugut AI. Risk of perforation after colonoscopy and sigmoidoscopy: a population-based study. J Natl Cancer Inst 2003; 95(3):230–236. pmid:12569145
- Warren JL, Klabunde CN, Mariotto AB, et al. Adverse events after outpatient colonoscopy in the Medicare population. Ann Intern Med 2009; 150(12):849–857, W152. pmid:19528563
- Quintero E, Carrillo M, Gimeno-García AZ, et al. Equivalency of fecal immunochemical tests and colonoscopy in familial colorectal cancer screening. Gastroenterology 2014; 147(5):1021–130.e1. doi:10.1053/j.gastro.2014.08.004
- Leddin D, Lieberman DA, Tse F, et al. Clinical practice guideline on screening for colorectal cancer in individuals with a family history of nonhereditary colorectal cancer or adenoma: the Canadian Association of Gastroenterology Banff Consensus. Gastroenterology 2018; 155(5):1325–1347.e3. doi:10.1053/j.gastro.2018.08.017
- Quintero E, Castells A, Bujanda L, et al; COLONPREV Study Investigators. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med 2012; 366(8):697–706. doi:10.1056/NEJMoa1108895
- Gupta S, Halm EA, Rockey DC, et al. Comparative effectiveness of fecal immunochemical test outreach, colonoscopy outreach, and usual care for boosting colorectal cancer screening among the underserved: a randomized clinical trial. JAMA Intern Med 2013; 173(18):1725–1732. doi:10.1001/jamainternmed.2013.9294
- Segnan N, Senore C, Andreoni B, et al; SCORE3 Working Group-Italy. Comparing attendance and detection rate of colonoscopy with sigmoidoscopy and FIT for colorectal cancer screening. Gastroenterology 2007; 132(7):2304–2312. doi:10.1053/j.gastro.2007.03.030
KEY POINTS
- Colorectal cancer rates are increasing in young individuals, with 10,000 new cases reported in 2017 in people ages 20 to 49. The evidence to support screening at ages 45 to 50 is not well established.
- FIT is noninvasive but requires high patient adherence and the ability to follow a multistep process. Preliminary results from one trial showed it inferior to colonoscopy for detecting colorectal cancer precursors.
- Colonoscopy allows visualization and removal of precursor lesions. A positive FIT result requires follow-up colonoscopy within 10 months.
Women’s health 2019: Osteoporosis, breast cancer, contraception, and hormone therapy
Keeping up with current evidence-based healthcare practices is key to providing good clinical care to patients. This review presents 5 vignettes that highlight key issues in women’s health: osteoporosis screening, hormonal contraceptive interactions with antibiotics, hormone replacement therapy in carriers of the BRCA1 gene mutation, risks associated with hormonal contraception, and breast cancer diagnosis using digital tomosynthesis in addition to digital mammography. Supporting articles, all published in 2017 and 2018, were selected from high-impact medical and women’s health journals.
OSTEOPOROSIS SCREENING FOR FRACTURE PREVENTION
A 60-year-old woman reports that her last menstrual period was 7 years ago. She has no history of falls or fractures, and she takes no medications. She smokes 10 cigarettes per day and drinks 3 to 4 alcoholic beverages on most days of the week. She is 5 feet 6 inches (170 cm) tall and weighs 107 lb. Should she be screened for osteoporosis?
Osteoporosis is underdiagnosed
It is estimated that, in the United States, 12.3 million individuals older than 50 will develop osteoporosis by 2020. Missed opportunities to screen high-risk individuals can lead to fractures, including fractures of the hip.1
Updated screening recommendations
In 2018, the US Preventive Services Task Force (USPSTF) developed and published evidence-based recommendations for osteoporosis screening to help providers identify and treat osteoporosis early to prevent fractures.2 Available evidence on screening and treatment in women and men were reviewed with the intention of updating the 2011 USPSTF recommendations. The review also evaluated risk assessment tools, screening intervals, and efficacy of screening and treatment in various subpopulations.
Since the 2011 recommendations, more data have become available on fracture risk assessment with or without bone mineral density measurements. In its 2018 report, the USPSTF recommends that postmenopausal women younger than 65 should undergo screening with a bone density test if their 10-year risk of major osteoporotic fracture is more than 8.4%. This is equivalent to the fracture risk of a 65-year-old white woman with no major risk factors for fracture (grade B recommendation—high certainty that the benefit is moderate, or moderate certainty that the benefit is moderate to substantial).2
Assessment of fracture risk
For postmenopausal women who are under age 65 and who have at least 1 risk factor for fracture, it is reasonable to use a clinical risk assessment tool to determine who should undergo screening with bone mineral density measurement. Risk factors associated with an increased risk of osteoporotic fractures include a parental history of hip fracture, smoking, intake of 3 or more alcoholic drinks per day, low body weight, malabsorption, rheumatoid arthritis, diabetes, and postmenopausal status (not using estrogen replacement). Medications should be carefully reviewed for those that can increase the risk of fractures, including steroids and antiestrogen treatments.
The 10-year risk of a major osteoporotic or hip fracture can be assessed using the Fractional Risk Assessment Tool (FRAX), available at www.sheffield.ac.uk/FRAX/. Other acceptable tools that perform similarly to FRAX include the Osteoporosis Risk Assessment Instrument (ORAI) (10 studies; N = 16,780), Osteoporosis Index of Risk (OSIRIS) (5 studies; N = 5,649), Osteoporosis Self-Assessment Tool (OST) (13 studies; N = 44,323), and Simple Calculated Osteoporosis Risk Estimation (SCORE) (8 studies; N = 15,362).
Should this patient be screened for osteoporosis?
Based on the FRAX, this patient’s 10-year risk of major osteoporosis fracture is 9.2%. She would benefit from osteoporosis screening with a bone density test.
DO ANTIBIOTICS REDUCE EFFECTIVENESS OF HORMONAL CONTRACEPTION?
A 27-year-old woman presents with a dog bite on her right hand and is started on oral antibiotics. She takes an oral contraceptive that contains 35 µg of ethinyl estradiol and 0.25 mg of norgestimate. She asks if she should use condoms while taking antibiotics.
The antibiotics rifampin and rifabutin are known inducers of the hepatic enzymes required for contraceptive steroid metabolism, whereas other antibiotics are not. Despite the lack of compelling evidence that broad-spectrum antibiotics interfere with the efficacy of hormonal contraception, most pharmacists recommend backup contraception for women who use concomitant antibiotics.3 This practice could lead to poor compliance with the contraceptive regimen, the antibiotic regimen, or both.3
Simmons et al3 conducted a systematic review of randomized and nonrandomized studies that assessed pregnancy rates, breakthrough bleeding, ovulation suppression, and hormone pharmacokinetics in women taking oral or vaginal hormonal contraceptives in combination with nonrifamycin antibiotics, including oral, intramuscular, and intravenous forms. Oral contraceptives used in the studies included a range of doses and progestins, but lowest-dose pills, such as those containing less than 30 µg ethinyl estradiol or less than 150 µg levonorgestrel, were not included.
The contraceptive formulations in this systematic review3 included oral contraceptive pills, emergency contraception pills, and the contraceptive vaginal ring. The effect of antibiotics on other nonoral contraceptives, such as the transdermal patch, injectables, and progestin implants was not studied.
Four observational studies3 evaluated pregnancy rates or hormonal contraception failure with any antibiotic use. In 2 of these 4 studies, there was no difference in pregnancy rates in women who used oral contraceptives with and without nonrifamycin antibiotics. However, ethinyl estradiol was shown to have increased clearance when administered with dirithromycin (a macrolide).3 Twenty-five of the studies reported measures of contraceptive effectiveness (ovulation) and pharmacokinetic outcomes.
There were no observed differences in ovulation suppression or breakthrough bleeding in any study that combined hormonal contraceptives with an antibiotic. Furthermore, there was no significant decrease in progestin pharmacokinetic parameters during coadministration with an antibiotic.3 Study limitations included small sample sizes and the observational nature of the data.
How would you counsel this patient?
Available evidence suggests that nonrifamycin antibiotics do not diminish the effectiveness of the vaginal contraceptive ring or an oral hormonal contraceptive that contains at least 30 µg of ethinyl estradiol or 150 µg of levonorgestrel. Current guidelines do not recommend the use of additional backup contraception, regardless of hormonal contraception dose or formulation.4 Likewise, the most recent guidance for dental practitioners (ie, from 2012) no longer advises women to use additional contraceptive protection when taking nonrifamycin antibiotics.5
In our practice, we discuss the option of additional protection when prescribing formulations with lower estrogen doses (< 30 µg), not only because of the limitations of the available data, but also because of the high rates of unintended pregnancy with typical use of combined hormonal contraceptives (9% per year, unrelated to use of antibiotics).4 However, if our patient would rather not use additional barrier methods, she can be reassured that concomitant nonrifamycin antibiotic use is unlikely to affect contraceptive effectiveness.
HORMONE REPLACEMENT THERAPY IN CARRIERS OF THE BRCA1 MUTATION
A 41-year-old healthy mother of 3 was recently found to be a carrier of the BRCA1 mutation. She is planning to undergo prophylactic bilateral salpingo-oophorectomy for ovarian cancer prevention. However, she is apprehensive about undergoing surgical menopause. Should she be started on hormone replacement therapy after oophorectomy? How would hormone replacement therapy affect her risk of breast cancer?
In females who carry the BRCA1 mutation, the cumulative risk of both ovarian and breast cancer approaches 44% (95% confidence interval [CI] 36%–53%) and 72% (95% CI 65%–79%) by age 80.6 Prophylactic salpingo-oophorectomy reduces the risk of breast cancer by 50% and the risk of ovarian cancer by 90%. Unfortunately, premature withdrawal of ovarian hormones has been associated with long-term adverse effects including significant vasomotor symptoms, decreased quality of life, sexual dysfunction, early mortality, bone loss, decline in mood and cognition, and poor cardiovascular outcomes.7 Many of these effects can be avoided or lessened with hormone replacement therapy.
Kotsopoulos et al8 conducted a longitudinal, prospective analysis of BRCA1 mutation carriers in a multicenter study between 1995 and 2017. The mean follow-up period was 7.6 years (range 0.4–22.1). The study assessed associations between the use of hormone replacement therapy and breast cancer risk in carriers of the BRCA1 mutation who underwent prophylactic salpingo-oophorectomy. Study participants did not have a personal history of cancer. Those with a history of prophylactic mastectomy were excluded.
Participants completed a series of questionnaires every 2 years, disclosing updates in personal medical, cancer, and reproductive history. The questionnaires also inquired about the use of hormone replacement therapy, including the type used (estrogen only, progestin only, estrogen plus progestin, other), brand name, duration of use, and dose and route of administration (pill, patch, suppository).
Of the 13,087 BRCA1 mutation carriers identified, 872 met the study criteria. Of those, 377 (43%) reported using some form of hormone replacement therapy after salpingo-oophorectomy, and 495 (57%) did not. The average duration of use was 3.9 years (range 0.5–19), with most (69%) using estrogen alone; 18% used other regimens, including estrogen plus progestin and progestin only. A small percentage of participants did not indicate which formulation they used. On average, women using hormone replacement therapy underwent prophylactic oophorectomy earlier than nonusers (age 43.0 vs 48.4; absolute difference 5.5 years, P < .001).
During follow-up, there was no significant difference noted in the proportion of women diagnosed with breast cancer between hormone replacement therapy users and nonusers (10.3 vs 10.7%; absolute difference 0.4%; P = .86). In fact, for each year of estrogen-containing hormone replacement therapy, there was an 18% reduction in breast cancer risk when oophorectomy was performed before age 45 (95% CI 0.69–0.97). The authors also noted a nonsignificant 14% trend toward an increase in breast cancer risk for each year of progestin use after oophorectomy when surgery was performed before age 45 (95% CI 0.9–1.46).
Although prophylactic hysterectomy was not recommended, the authors noted that hysterectomy would eliminate the need for progestin-containing hormone replacement therapy. For those who underwent oophorectomy after age 45, hormone replacement therapy did not increase or decrease the risk of breast cancer.7
A meta-analysis by Marchetti et al9 also supports the safety of hormone replacement therapy after risk-reducing salpingo-oophorectomy. Three studies that included 1,100 patients were analyzed (including the Kotsopoulos study8 noted above). There was a nonsignificant decrease in breast cancer risk in women on estrogen-only hormone replacement therapy compared with women on estrogen-plus-progestin therapy (odds ratio 0.53, 95% CI 0.25–1.15). Overall, the authors regarded hormone replacement therapy as a safe therapeutic option after prophylactic salpingo-oophorectomy in carriers of the BRCA1 and BRCA2 mutations.9
In a case-control study published in 2016,10 hormone replacement therapy was assessed in 432 postmenopausal BRCA1 mutation carriers with invasive breast cancer (cases) and in 432 BRCA1 mutation carriers without a history of breast cancer (controls). Results showed no difference in breast cancer risk between hormone replacement therapy users and nonusers.10
Rebbeck et al11 evaluated short-term hormone replacement therapy in BRCA1 and BRCA2 gene-mutation carriers after they underwent prophylactic salpingo-oophorectomy. The results showed that hormone replacement did not affect the breast cancer risk-reduction conferred with prophylactic bilateral salpingo-oophorectomy.
Johansen et al12 evaluated hormone replacement therapy in premenopausal women after prophylactic salpingo-oophorectomy. They studied 324 carriers of BRCA gene mutations after they underwent prophylactic salpingo-oophorectomy and a subset of 950 controls who had bilateral salpingo-oophorectomy for reasons unrelated to cancer. In both groups, hormone replacement therapy was underutilized. The authors recommended using it when clinically indicated.
Should your patient start hormone replacement therapy?
This patient is healthy, and in the absence of contraindications, systemic hormone replacement therapy after prophylactic oophorectomy could mitigate the potential adverse effects of surgically induced menopause. The patient can be reassured that estrogen-containing short-term hormone replacement therapy is unlikely to increase her breast cancer risk.
HORMONAL CONTRACEPTION AND THE RISK OF BREAST CANCER
A 44-year-old woman presents to your office for an annual visit. She is sexually active but does not wish to become pregnant. She has a family history of breast cancer: her mother was diagnosed at age 53. She is interested in an oral contraceptive to prevent pregnancy and acne. However, she is nervous about being on any contraceptive that may increase her risk of breast cancer.
To date, studies assessing the effect of hormonal contraception on the risk of breast cancer have produced inconsistent results. Although most studies have shown no associated risk, a few have shown a temporary 20% to 30% increased risk of breast cancer during use.13,14 Case-controlled studies that reported an association between hormonal contraception and breast cancer included populations taking higher-dose combination pills, which are no longer prescribed. Most studies do not evaluate specific formulations of hormonal contraception, and little is known about effects associated with intrauterine devices or progestin-only contraception.
A prospective study performed by Mørch et al13 followed more than 1 million reproductive-aged women for a mean of 10.9 years. The Danish Cancer Registry was used to identify cases of invasive breast cancer. Women who used hormonal contraceptives had a relative risk of breast cancer of 1.20 compared with women not on hormonal contraception (95% CI 1.14–1.26). The study suggested that those who had been on contraceptive agents for more than 5 years had an increased risk and that this risk remained for 5 years after the agents were discontinued. Conversely, no increased risk of cancer was noted in those who used hormonal contraception for less than 5 years. No notable differences were seen among various formulations.
For women using the levonorgestrel-containing intrauterine device, the relative risk of breast cancer was 1.21 (95% CI 1.11–1.33). A few cancers were noted in those who used the progestin-only implant or those using depot medroxyprogesterone acetate. While the study showed an increased relative risk of breast cancer, the absolute risk was low—13 cases per 100,000, or approximately 1 additional case of breast cancer per 7,690 per year.13
This study had several important limitations. The authors did not adjust for common breast cancer risk factors including age at menarche, alcohol use, or breastfeeding. Additionally, the study did not account for the use of hormonal contraception before the study period and conversely, did not account for women who may have stopped taking their contraceptive despite their prescribed duration. The frequency of mammography was not explicitly noted, which could have shifted results for women who had more aggressive screening.
It is also noteworthy that the use of high-dose systemic progestins was not associated with an increased risk, whereas the levonorgestrel intrauterine device, which contains only 1/20th the dose of a low-dose oral contraceptive pill, was associated with an increased risk. This discrepancy in risk warrants further investigation, and clinicians should be aware that this inconsistency needs validation before changing clinical practice.
In an observational cohort study,15 more than 100,000 women ages 50 to 71 were followed prospectively for 15 years to evaluate the association between hormonal contraceptive use and the risk of gynecologic and breast cancers. In this study, the duration of hormonal contraceptive use, smoking status, alcohol use, body mass index, physical activity, and family history of cancer were recorded. Long-term hormonal contraceptive use reduced ovarian and endometrial cancer risks by 40% and 34%, respectively, with no increase in breast cancer risk regardless of family history.
How would you counsel the patient?
The patient should be educated on the benefits of hormonal contraception that extend beyond pregnancy prevention, including regulation of menses, improved acne, decreased risk of endometrial and ovarian cancer, and likely reductions in colorectal cancer and overall mortality risk.13–16 Further, after their own systematic review of the data assessing risk of breast cancer with hormonal contraception, the US Centers for Disease Control and Prevention state in their guidelines that all contraceptives may be used without limitation in those who have a family history of breast cancer.4 Any potential increased risk of breast cancer in women using hormonal contraception is small and would not outweigh the benefits associated with use.
One must consider the impact of an unintended pregnancy in such women, including effects on the health of the fetus and mother. Recent reports on the increasing rates of maternal death in the US (23.8 of 100,000 live births) serve as a reminder of the complications that can arise with pregnancy, especially if a mother’s health is not optimized before conception.17
MAMMOGRAPHY PLUS TOMOSYNTHESIS VS MAMMOGRAPHY ALONE
The same 44-year-old patient now inquires about screening for breast cancer. She is curious about 3-dimensional mammography and whether it would be a better screening test for her.
Digital breast tomosynthesis (DBT) is a newer imaging modality that provides a 3-dimensional reconstruction of the breast using low-dose x-ray imaging. Some studies have shown that combining DBT with digital mammography may be superior to digital mammography alone in detecting cancers.18 However, digital mammography is currently the gold standard for breast cancer screening and is the only test proven to reduce mortality.18,19
In a retrospective US study of 13 medical centers,20 breast cancer detection rates increased by 41% the year after DBT was introduced, from 2.9 to 4.1 per 1,000 cases. DBT was associated with 16 fewer patients recalled for repeat imaging out of 1,000 women screened (as opposed to mammography alone). Two European studies similarly suggested an increase in cancer detection with lower recall rates.21,22
Is 3-D mammography a better option?
In a 2-arm study by Pattacini et al,18 nearly 20,000 women ages 45 to 70 were randomized to undergo either digital mammography or digital mammography plus DBT for primary breast cancer screening. Women were enrolled over a 2-year period and were followed for 4.5 years, and the development of a primary invasive cancer was the primary end point. Recall rates, reading times, and radiation doses were also compared between the 2 groups.
Overall, the cancer detection rate was higher in the digital mammography plus DBT arm compared with digital mammography alone (8.6 vs 4.5 per 1,000). The detection rates were higher in the combined screening group among all age subgroups, with relative risks ranging from 1.83 to 2.04 (P = .93). The recall rate was 3.5% in the 2 arms, with relative risks ranging from 0.93 to 1.11 (P = .52). There was a reduction in the number of false positives seen in women undergoing digital mammography plus DBT when compared with digital mammography alone, from 30 per 1,000 to 27 per 1,000.
Detection of ductal carcinoma in situ increased in the experimental arm (relative detection 2.80, 95% CI 1.01–7.65) compared with invasive cancers. Comparing radiation, the dose was 2.3 times higher in those who underwent digital mammography plus DBT. The average reading times for digital mammography alone were 20 to 85 seconds; adding DBT added 35 to 81 seconds.19
Should you advise 3-D mammography?
The patient should be educated on the benefits of both digital mammography alone and digital mammography plus DBT. The use of digital mammography plus DBT has been supported in various studies and has been shown to increase cancer detection rates, although data are still conflicting regarding recall rates.19,20 More studies are needed to determine its effect on breast cancer morality.
Routine use of DBT in women with or without dense breast tissue has not been recommended by organizations such as the USPSTF and the American College of Obstetricians and Gynecologists.23,24 While there is an increased dose of radiation, it still falls below the US Food and Drug Administration limits and should not be the sole barrier to use.
- Cauley JA. Screening for osteoporosis. JAMA 2018; 319(24):2483–2485. doi:10.1001/jama.2018.5722
- US Preventive Services Task Force, Curry SJ, Krist AH, Owens DK, et al. Screening for osteoporosis to prevent fractures: US Preventive Services Task Force recommendation statement. JAMA 2018; 319(24):2521–2531. doi:10.1001/jama.2018.7498
- Simmons KB, Haddad LB, Nanda K, Curtis KM. Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review. Am J Obstet Gynecol 2018; 218(1):88–97.e14. doi:10.1016/j.ajog.2017.07.003
- Curtis KM, Tepper NK, Jatlaoui TC, et al. US Medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep 2016; 65(3):1–103. doi:10.15585/mmwr.rr6503a1
- Taylor J, Pemberton MN. Antibiotics and oral contraceptives: new considerations for dental practice. Br Dent J 2012; 212(10):481–483. doi:10.1038/sj.bdj.2012.414
- Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 2017; 317(23):2402–2416. doi:10.1001/jama.2017.7112
- Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long-term health consequences of premature or early menopause and considerations for management. Climacteric 2015; 18(4):483–491. doi:10.3109/13697137.2015.1020484
- Kotsopoulos J, Gronwald J, Karlan BY, et al; Hereditary Breast Cancer Clinical Study Group. Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. JAMA Oncol 2018; 4(8):1059–1065. doi:10.1001/jamaoncol.2018.0211
- Marchetti C, De Felice F, Boccia S, et al. Hormone replacement therapy after prophylactic risk reducing salpingo-oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a meta-analysis. Crit Rev Oncol Hematol 2018; 132:111–115. doi:10.1016/j.critrevonc.2018.09.018
- Kotsopoulos J, Huzarski T, Gronwald J, et al. Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case-control study. Breast Cancer Res Treat 2016; 155(2):365–373. doi:10.1007/s10549-016-3685-3
- Rebbeck TR, Friebel T, Wagner T, et al; PROSE Study Group. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2005; 23(31):7804–7810. doi:10.1200/JCO.2004.00.8151
- Johansen N, Liavaag AH, Iversen OE, Dørum A, Braaten T, Michelsen TM. Use of hormone replacement therapy after risk-reducing salpingo-oophorectomy. Acta Obstet Gynecol Scand 2017; 96(5):547–555. doi:10.1111/aogs.13120
- Mørch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard Ø. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med 2017; 377(23):2228–2239. doi:10.1056/NEJMoa1700732
- Batur P, Sikka S, McNamara M. Contraception update: extended use of long acting methods, hormonal contraception risks, and over the counter access. J Womens Health (Larchmt) 2018. doi:10.1089/jwh.2018.7391. [Epub ahead of print]
- Michels KA, Pfeiffer RM, Brinton LA, Trabert B. Modification of the associations between duration of oral contraceptive use and ovarian, endometrial, breast, and colorectal cancers. JAMA Oncol 2018; 4(4):516–521. doi:10.1001/jamaoncol.2017.4942
- Iversen L, Fielding S, Lidegaard Ø, Mørch LS, Skovlund CW, Hannaford PC. Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study. BMJ 2018; 362:k3609. doi:10.1136/bmj.k3609
- MacDorman MF, Declercq E, Cabral H, Morton C. Recent increases in the US maternal mortality rate: disentangling trends from measurement issues. Obstet Gynecol 2016; 128(3):447–455. doi:10.1097/AOG.0000000000001556
- Pattacini P, Nitrosi A, Giorgi Rossi P, et al; RETomo Working Group. Digital mammography versus digital mammography plus tomosynthesis for breast cancer screening: the Reggio Emilia tomosynthesis randomized trial. Radiology 2018; 288(2):375–385. doi:10.1148/radiol.2018172119
- Pace L, Keating NL. A systematic assessment of benefits and risks to guide breast cancer screening decisions. JAMA 2014; 311(13):1327–1335. doi:10.1001/jama.2014.1398
- Friedewald SM, Rafferty EA, Rose SL, et al. Breast cancer screening using tomosynthesis in combination with digital mammography. JAMA 2014; 311(24):2499–2507. doi:10.1001/jama.2014.6095
- Skaane P, Bandos AI, Gullien R, et al. Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program. Radiology 2013; 267(1):47–56. doi:10.1148/radiol.12121373
- Ciatto S, Houssami N, Bernardi D, et al. Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study. Lancet Oncol 2013; 14(7):583–589. doi:10.1016/S1470-2045(13)70134-7
- US Preventive Services Task Force. Final recommendation statement: breast cancer: screening. www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/breast-cancer-screening1. Accessed May 13, 2019.
- American College of Obstetricians and Gynecologists. Breast cancer risk assessment and screening in average-risk women. www.acog.org/Clinical-Guidance-and-Publications/Practice-Bulletins/Committee-on-Practice-Bulletins-Gynecology/Breast-Cancer-Risk-Assessment-and-Screening-in-Average-Risk-Women?IsMobileSet=false#5. Accessed May 13, 2019.
Keeping up with current evidence-based healthcare practices is key to providing good clinical care to patients. This review presents 5 vignettes that highlight key issues in women’s health: osteoporosis screening, hormonal contraceptive interactions with antibiotics, hormone replacement therapy in carriers of the BRCA1 gene mutation, risks associated with hormonal contraception, and breast cancer diagnosis using digital tomosynthesis in addition to digital mammography. Supporting articles, all published in 2017 and 2018, were selected from high-impact medical and women’s health journals.
OSTEOPOROSIS SCREENING FOR FRACTURE PREVENTION
A 60-year-old woman reports that her last menstrual period was 7 years ago. She has no history of falls or fractures, and she takes no medications. She smokes 10 cigarettes per day and drinks 3 to 4 alcoholic beverages on most days of the week. She is 5 feet 6 inches (170 cm) tall and weighs 107 lb. Should she be screened for osteoporosis?
Osteoporosis is underdiagnosed
It is estimated that, in the United States, 12.3 million individuals older than 50 will develop osteoporosis by 2020. Missed opportunities to screen high-risk individuals can lead to fractures, including fractures of the hip.1
Updated screening recommendations
In 2018, the US Preventive Services Task Force (USPSTF) developed and published evidence-based recommendations for osteoporosis screening to help providers identify and treat osteoporosis early to prevent fractures.2 Available evidence on screening and treatment in women and men were reviewed with the intention of updating the 2011 USPSTF recommendations. The review also evaluated risk assessment tools, screening intervals, and efficacy of screening and treatment in various subpopulations.
Since the 2011 recommendations, more data have become available on fracture risk assessment with or without bone mineral density measurements. In its 2018 report, the USPSTF recommends that postmenopausal women younger than 65 should undergo screening with a bone density test if their 10-year risk of major osteoporotic fracture is more than 8.4%. This is equivalent to the fracture risk of a 65-year-old white woman with no major risk factors for fracture (grade B recommendation—high certainty that the benefit is moderate, or moderate certainty that the benefit is moderate to substantial).2
Assessment of fracture risk
For postmenopausal women who are under age 65 and who have at least 1 risk factor for fracture, it is reasonable to use a clinical risk assessment tool to determine who should undergo screening with bone mineral density measurement. Risk factors associated with an increased risk of osteoporotic fractures include a parental history of hip fracture, smoking, intake of 3 or more alcoholic drinks per day, low body weight, malabsorption, rheumatoid arthritis, diabetes, and postmenopausal status (not using estrogen replacement). Medications should be carefully reviewed for those that can increase the risk of fractures, including steroids and antiestrogen treatments.
The 10-year risk of a major osteoporotic or hip fracture can be assessed using the Fractional Risk Assessment Tool (FRAX), available at www.sheffield.ac.uk/FRAX/. Other acceptable tools that perform similarly to FRAX include the Osteoporosis Risk Assessment Instrument (ORAI) (10 studies; N = 16,780), Osteoporosis Index of Risk (OSIRIS) (5 studies; N = 5,649), Osteoporosis Self-Assessment Tool (OST) (13 studies; N = 44,323), and Simple Calculated Osteoporosis Risk Estimation (SCORE) (8 studies; N = 15,362).
Should this patient be screened for osteoporosis?
Based on the FRAX, this patient’s 10-year risk of major osteoporosis fracture is 9.2%. She would benefit from osteoporosis screening with a bone density test.
DO ANTIBIOTICS REDUCE EFFECTIVENESS OF HORMONAL CONTRACEPTION?
A 27-year-old woman presents with a dog bite on her right hand and is started on oral antibiotics. She takes an oral contraceptive that contains 35 µg of ethinyl estradiol and 0.25 mg of norgestimate. She asks if she should use condoms while taking antibiotics.
The antibiotics rifampin and rifabutin are known inducers of the hepatic enzymes required for contraceptive steroid metabolism, whereas other antibiotics are not. Despite the lack of compelling evidence that broad-spectrum antibiotics interfere with the efficacy of hormonal contraception, most pharmacists recommend backup contraception for women who use concomitant antibiotics.3 This practice could lead to poor compliance with the contraceptive regimen, the antibiotic regimen, or both.3
Simmons et al3 conducted a systematic review of randomized and nonrandomized studies that assessed pregnancy rates, breakthrough bleeding, ovulation suppression, and hormone pharmacokinetics in women taking oral or vaginal hormonal contraceptives in combination with nonrifamycin antibiotics, including oral, intramuscular, and intravenous forms. Oral contraceptives used in the studies included a range of doses and progestins, but lowest-dose pills, such as those containing less than 30 µg ethinyl estradiol or less than 150 µg levonorgestrel, were not included.
The contraceptive formulations in this systematic review3 included oral contraceptive pills, emergency contraception pills, and the contraceptive vaginal ring. The effect of antibiotics on other nonoral contraceptives, such as the transdermal patch, injectables, and progestin implants was not studied.
Four observational studies3 evaluated pregnancy rates or hormonal contraception failure with any antibiotic use. In 2 of these 4 studies, there was no difference in pregnancy rates in women who used oral contraceptives with and without nonrifamycin antibiotics. However, ethinyl estradiol was shown to have increased clearance when administered with dirithromycin (a macrolide).3 Twenty-five of the studies reported measures of contraceptive effectiveness (ovulation) and pharmacokinetic outcomes.
There were no observed differences in ovulation suppression or breakthrough bleeding in any study that combined hormonal contraceptives with an antibiotic. Furthermore, there was no significant decrease in progestin pharmacokinetic parameters during coadministration with an antibiotic.3 Study limitations included small sample sizes and the observational nature of the data.
How would you counsel this patient?
Available evidence suggests that nonrifamycin antibiotics do not diminish the effectiveness of the vaginal contraceptive ring or an oral hormonal contraceptive that contains at least 30 µg of ethinyl estradiol or 150 µg of levonorgestrel. Current guidelines do not recommend the use of additional backup contraception, regardless of hormonal contraception dose or formulation.4 Likewise, the most recent guidance for dental practitioners (ie, from 2012) no longer advises women to use additional contraceptive protection when taking nonrifamycin antibiotics.5
In our practice, we discuss the option of additional protection when prescribing formulations with lower estrogen doses (< 30 µg), not only because of the limitations of the available data, but also because of the high rates of unintended pregnancy with typical use of combined hormonal contraceptives (9% per year, unrelated to use of antibiotics).4 However, if our patient would rather not use additional barrier methods, she can be reassured that concomitant nonrifamycin antibiotic use is unlikely to affect contraceptive effectiveness.
HORMONE REPLACEMENT THERAPY IN CARRIERS OF THE BRCA1 MUTATION
A 41-year-old healthy mother of 3 was recently found to be a carrier of the BRCA1 mutation. She is planning to undergo prophylactic bilateral salpingo-oophorectomy for ovarian cancer prevention. However, she is apprehensive about undergoing surgical menopause. Should she be started on hormone replacement therapy after oophorectomy? How would hormone replacement therapy affect her risk of breast cancer?
In females who carry the BRCA1 mutation, the cumulative risk of both ovarian and breast cancer approaches 44% (95% confidence interval [CI] 36%–53%) and 72% (95% CI 65%–79%) by age 80.6 Prophylactic salpingo-oophorectomy reduces the risk of breast cancer by 50% and the risk of ovarian cancer by 90%. Unfortunately, premature withdrawal of ovarian hormones has been associated with long-term adverse effects including significant vasomotor symptoms, decreased quality of life, sexual dysfunction, early mortality, bone loss, decline in mood and cognition, and poor cardiovascular outcomes.7 Many of these effects can be avoided or lessened with hormone replacement therapy.
Kotsopoulos et al8 conducted a longitudinal, prospective analysis of BRCA1 mutation carriers in a multicenter study between 1995 and 2017. The mean follow-up period was 7.6 years (range 0.4–22.1). The study assessed associations between the use of hormone replacement therapy and breast cancer risk in carriers of the BRCA1 mutation who underwent prophylactic salpingo-oophorectomy. Study participants did not have a personal history of cancer. Those with a history of prophylactic mastectomy were excluded.
Participants completed a series of questionnaires every 2 years, disclosing updates in personal medical, cancer, and reproductive history. The questionnaires also inquired about the use of hormone replacement therapy, including the type used (estrogen only, progestin only, estrogen plus progestin, other), brand name, duration of use, and dose and route of administration (pill, patch, suppository).
Of the 13,087 BRCA1 mutation carriers identified, 872 met the study criteria. Of those, 377 (43%) reported using some form of hormone replacement therapy after salpingo-oophorectomy, and 495 (57%) did not. The average duration of use was 3.9 years (range 0.5–19), with most (69%) using estrogen alone; 18% used other regimens, including estrogen plus progestin and progestin only. A small percentage of participants did not indicate which formulation they used. On average, women using hormone replacement therapy underwent prophylactic oophorectomy earlier than nonusers (age 43.0 vs 48.4; absolute difference 5.5 years, P < .001).
During follow-up, there was no significant difference noted in the proportion of women diagnosed with breast cancer between hormone replacement therapy users and nonusers (10.3 vs 10.7%; absolute difference 0.4%; P = .86). In fact, for each year of estrogen-containing hormone replacement therapy, there was an 18% reduction in breast cancer risk when oophorectomy was performed before age 45 (95% CI 0.69–0.97). The authors also noted a nonsignificant 14% trend toward an increase in breast cancer risk for each year of progestin use after oophorectomy when surgery was performed before age 45 (95% CI 0.9–1.46).
Although prophylactic hysterectomy was not recommended, the authors noted that hysterectomy would eliminate the need for progestin-containing hormone replacement therapy. For those who underwent oophorectomy after age 45, hormone replacement therapy did not increase or decrease the risk of breast cancer.7
A meta-analysis by Marchetti et al9 also supports the safety of hormone replacement therapy after risk-reducing salpingo-oophorectomy. Three studies that included 1,100 patients were analyzed (including the Kotsopoulos study8 noted above). There was a nonsignificant decrease in breast cancer risk in women on estrogen-only hormone replacement therapy compared with women on estrogen-plus-progestin therapy (odds ratio 0.53, 95% CI 0.25–1.15). Overall, the authors regarded hormone replacement therapy as a safe therapeutic option after prophylactic salpingo-oophorectomy in carriers of the BRCA1 and BRCA2 mutations.9
In a case-control study published in 2016,10 hormone replacement therapy was assessed in 432 postmenopausal BRCA1 mutation carriers with invasive breast cancer (cases) and in 432 BRCA1 mutation carriers without a history of breast cancer (controls). Results showed no difference in breast cancer risk between hormone replacement therapy users and nonusers.10
Rebbeck et al11 evaluated short-term hormone replacement therapy in BRCA1 and BRCA2 gene-mutation carriers after they underwent prophylactic salpingo-oophorectomy. The results showed that hormone replacement did not affect the breast cancer risk-reduction conferred with prophylactic bilateral salpingo-oophorectomy.
Johansen et al12 evaluated hormone replacement therapy in premenopausal women after prophylactic salpingo-oophorectomy. They studied 324 carriers of BRCA gene mutations after they underwent prophylactic salpingo-oophorectomy and a subset of 950 controls who had bilateral salpingo-oophorectomy for reasons unrelated to cancer. In both groups, hormone replacement therapy was underutilized. The authors recommended using it when clinically indicated.
Should your patient start hormone replacement therapy?
This patient is healthy, and in the absence of contraindications, systemic hormone replacement therapy after prophylactic oophorectomy could mitigate the potential adverse effects of surgically induced menopause. The patient can be reassured that estrogen-containing short-term hormone replacement therapy is unlikely to increase her breast cancer risk.
HORMONAL CONTRACEPTION AND THE RISK OF BREAST CANCER
A 44-year-old woman presents to your office for an annual visit. She is sexually active but does not wish to become pregnant. She has a family history of breast cancer: her mother was diagnosed at age 53. She is interested in an oral contraceptive to prevent pregnancy and acne. However, she is nervous about being on any contraceptive that may increase her risk of breast cancer.
To date, studies assessing the effect of hormonal contraception on the risk of breast cancer have produced inconsistent results. Although most studies have shown no associated risk, a few have shown a temporary 20% to 30% increased risk of breast cancer during use.13,14 Case-controlled studies that reported an association between hormonal contraception and breast cancer included populations taking higher-dose combination pills, which are no longer prescribed. Most studies do not evaluate specific formulations of hormonal contraception, and little is known about effects associated with intrauterine devices or progestin-only contraception.
A prospective study performed by Mørch et al13 followed more than 1 million reproductive-aged women for a mean of 10.9 years. The Danish Cancer Registry was used to identify cases of invasive breast cancer. Women who used hormonal contraceptives had a relative risk of breast cancer of 1.20 compared with women not on hormonal contraception (95% CI 1.14–1.26). The study suggested that those who had been on contraceptive agents for more than 5 years had an increased risk and that this risk remained for 5 years after the agents were discontinued. Conversely, no increased risk of cancer was noted in those who used hormonal contraception for less than 5 years. No notable differences were seen among various formulations.
For women using the levonorgestrel-containing intrauterine device, the relative risk of breast cancer was 1.21 (95% CI 1.11–1.33). A few cancers were noted in those who used the progestin-only implant or those using depot medroxyprogesterone acetate. While the study showed an increased relative risk of breast cancer, the absolute risk was low—13 cases per 100,000, or approximately 1 additional case of breast cancer per 7,690 per year.13
This study had several important limitations. The authors did not adjust for common breast cancer risk factors including age at menarche, alcohol use, or breastfeeding. Additionally, the study did not account for the use of hormonal contraception before the study period and conversely, did not account for women who may have stopped taking their contraceptive despite their prescribed duration. The frequency of mammography was not explicitly noted, which could have shifted results for women who had more aggressive screening.
It is also noteworthy that the use of high-dose systemic progestins was not associated with an increased risk, whereas the levonorgestrel intrauterine device, which contains only 1/20th the dose of a low-dose oral contraceptive pill, was associated with an increased risk. This discrepancy in risk warrants further investigation, and clinicians should be aware that this inconsistency needs validation before changing clinical practice.
In an observational cohort study,15 more than 100,000 women ages 50 to 71 were followed prospectively for 15 years to evaluate the association between hormonal contraceptive use and the risk of gynecologic and breast cancers. In this study, the duration of hormonal contraceptive use, smoking status, alcohol use, body mass index, physical activity, and family history of cancer were recorded. Long-term hormonal contraceptive use reduced ovarian and endometrial cancer risks by 40% and 34%, respectively, with no increase in breast cancer risk regardless of family history.
How would you counsel the patient?
The patient should be educated on the benefits of hormonal contraception that extend beyond pregnancy prevention, including regulation of menses, improved acne, decreased risk of endometrial and ovarian cancer, and likely reductions in colorectal cancer and overall mortality risk.13–16 Further, after their own systematic review of the data assessing risk of breast cancer with hormonal contraception, the US Centers for Disease Control and Prevention state in their guidelines that all contraceptives may be used without limitation in those who have a family history of breast cancer.4 Any potential increased risk of breast cancer in women using hormonal contraception is small and would not outweigh the benefits associated with use.
One must consider the impact of an unintended pregnancy in such women, including effects on the health of the fetus and mother. Recent reports on the increasing rates of maternal death in the US (23.8 of 100,000 live births) serve as a reminder of the complications that can arise with pregnancy, especially if a mother’s health is not optimized before conception.17
MAMMOGRAPHY PLUS TOMOSYNTHESIS VS MAMMOGRAPHY ALONE
The same 44-year-old patient now inquires about screening for breast cancer. She is curious about 3-dimensional mammography and whether it would be a better screening test for her.
Digital breast tomosynthesis (DBT) is a newer imaging modality that provides a 3-dimensional reconstruction of the breast using low-dose x-ray imaging. Some studies have shown that combining DBT with digital mammography may be superior to digital mammography alone in detecting cancers.18 However, digital mammography is currently the gold standard for breast cancer screening and is the only test proven to reduce mortality.18,19
In a retrospective US study of 13 medical centers,20 breast cancer detection rates increased by 41% the year after DBT was introduced, from 2.9 to 4.1 per 1,000 cases. DBT was associated with 16 fewer patients recalled for repeat imaging out of 1,000 women screened (as opposed to mammography alone). Two European studies similarly suggested an increase in cancer detection with lower recall rates.21,22
Is 3-D mammography a better option?
In a 2-arm study by Pattacini et al,18 nearly 20,000 women ages 45 to 70 were randomized to undergo either digital mammography or digital mammography plus DBT for primary breast cancer screening. Women were enrolled over a 2-year period and were followed for 4.5 years, and the development of a primary invasive cancer was the primary end point. Recall rates, reading times, and radiation doses were also compared between the 2 groups.
Overall, the cancer detection rate was higher in the digital mammography plus DBT arm compared with digital mammography alone (8.6 vs 4.5 per 1,000). The detection rates were higher in the combined screening group among all age subgroups, with relative risks ranging from 1.83 to 2.04 (P = .93). The recall rate was 3.5% in the 2 arms, with relative risks ranging from 0.93 to 1.11 (P = .52). There was a reduction in the number of false positives seen in women undergoing digital mammography plus DBT when compared with digital mammography alone, from 30 per 1,000 to 27 per 1,000.
Detection of ductal carcinoma in situ increased in the experimental arm (relative detection 2.80, 95% CI 1.01–7.65) compared with invasive cancers. Comparing radiation, the dose was 2.3 times higher in those who underwent digital mammography plus DBT. The average reading times for digital mammography alone were 20 to 85 seconds; adding DBT added 35 to 81 seconds.19
Should you advise 3-D mammography?
The patient should be educated on the benefits of both digital mammography alone and digital mammography plus DBT. The use of digital mammography plus DBT has been supported in various studies and has been shown to increase cancer detection rates, although data are still conflicting regarding recall rates.19,20 More studies are needed to determine its effect on breast cancer morality.
Routine use of DBT in women with or without dense breast tissue has not been recommended by organizations such as the USPSTF and the American College of Obstetricians and Gynecologists.23,24 While there is an increased dose of radiation, it still falls below the US Food and Drug Administration limits and should not be the sole barrier to use.
Keeping up with current evidence-based healthcare practices is key to providing good clinical care to patients. This review presents 5 vignettes that highlight key issues in women’s health: osteoporosis screening, hormonal contraceptive interactions with antibiotics, hormone replacement therapy in carriers of the BRCA1 gene mutation, risks associated with hormonal contraception, and breast cancer diagnosis using digital tomosynthesis in addition to digital mammography. Supporting articles, all published in 2017 and 2018, were selected from high-impact medical and women’s health journals.
OSTEOPOROSIS SCREENING FOR FRACTURE PREVENTION
A 60-year-old woman reports that her last menstrual period was 7 years ago. She has no history of falls or fractures, and she takes no medications. She smokes 10 cigarettes per day and drinks 3 to 4 alcoholic beverages on most days of the week. She is 5 feet 6 inches (170 cm) tall and weighs 107 lb. Should she be screened for osteoporosis?
Osteoporosis is underdiagnosed
It is estimated that, in the United States, 12.3 million individuals older than 50 will develop osteoporosis by 2020. Missed opportunities to screen high-risk individuals can lead to fractures, including fractures of the hip.1
Updated screening recommendations
In 2018, the US Preventive Services Task Force (USPSTF) developed and published evidence-based recommendations for osteoporosis screening to help providers identify and treat osteoporosis early to prevent fractures.2 Available evidence on screening and treatment in women and men were reviewed with the intention of updating the 2011 USPSTF recommendations. The review also evaluated risk assessment tools, screening intervals, and efficacy of screening and treatment in various subpopulations.
Since the 2011 recommendations, more data have become available on fracture risk assessment with or without bone mineral density measurements. In its 2018 report, the USPSTF recommends that postmenopausal women younger than 65 should undergo screening with a bone density test if their 10-year risk of major osteoporotic fracture is more than 8.4%. This is equivalent to the fracture risk of a 65-year-old white woman with no major risk factors for fracture (grade B recommendation—high certainty that the benefit is moderate, or moderate certainty that the benefit is moderate to substantial).2
Assessment of fracture risk
For postmenopausal women who are under age 65 and who have at least 1 risk factor for fracture, it is reasonable to use a clinical risk assessment tool to determine who should undergo screening with bone mineral density measurement. Risk factors associated with an increased risk of osteoporotic fractures include a parental history of hip fracture, smoking, intake of 3 or more alcoholic drinks per day, low body weight, malabsorption, rheumatoid arthritis, diabetes, and postmenopausal status (not using estrogen replacement). Medications should be carefully reviewed for those that can increase the risk of fractures, including steroids and antiestrogen treatments.
The 10-year risk of a major osteoporotic or hip fracture can be assessed using the Fractional Risk Assessment Tool (FRAX), available at www.sheffield.ac.uk/FRAX/. Other acceptable tools that perform similarly to FRAX include the Osteoporosis Risk Assessment Instrument (ORAI) (10 studies; N = 16,780), Osteoporosis Index of Risk (OSIRIS) (5 studies; N = 5,649), Osteoporosis Self-Assessment Tool (OST) (13 studies; N = 44,323), and Simple Calculated Osteoporosis Risk Estimation (SCORE) (8 studies; N = 15,362).
Should this patient be screened for osteoporosis?
Based on the FRAX, this patient’s 10-year risk of major osteoporosis fracture is 9.2%. She would benefit from osteoporosis screening with a bone density test.
DO ANTIBIOTICS REDUCE EFFECTIVENESS OF HORMONAL CONTRACEPTION?
A 27-year-old woman presents with a dog bite on her right hand and is started on oral antibiotics. She takes an oral contraceptive that contains 35 µg of ethinyl estradiol and 0.25 mg of norgestimate. She asks if she should use condoms while taking antibiotics.
The antibiotics rifampin and rifabutin are known inducers of the hepatic enzymes required for contraceptive steroid metabolism, whereas other antibiotics are not. Despite the lack of compelling evidence that broad-spectrum antibiotics interfere with the efficacy of hormonal contraception, most pharmacists recommend backup contraception for women who use concomitant antibiotics.3 This practice could lead to poor compliance with the contraceptive regimen, the antibiotic regimen, or both.3
Simmons et al3 conducted a systematic review of randomized and nonrandomized studies that assessed pregnancy rates, breakthrough bleeding, ovulation suppression, and hormone pharmacokinetics in women taking oral or vaginal hormonal contraceptives in combination with nonrifamycin antibiotics, including oral, intramuscular, and intravenous forms. Oral contraceptives used in the studies included a range of doses and progestins, but lowest-dose pills, such as those containing less than 30 µg ethinyl estradiol or less than 150 µg levonorgestrel, were not included.
The contraceptive formulations in this systematic review3 included oral contraceptive pills, emergency contraception pills, and the contraceptive vaginal ring. The effect of antibiotics on other nonoral contraceptives, such as the transdermal patch, injectables, and progestin implants was not studied.
Four observational studies3 evaluated pregnancy rates or hormonal contraception failure with any antibiotic use. In 2 of these 4 studies, there was no difference in pregnancy rates in women who used oral contraceptives with and without nonrifamycin antibiotics. However, ethinyl estradiol was shown to have increased clearance when administered with dirithromycin (a macrolide).3 Twenty-five of the studies reported measures of contraceptive effectiveness (ovulation) and pharmacokinetic outcomes.
There were no observed differences in ovulation suppression or breakthrough bleeding in any study that combined hormonal contraceptives with an antibiotic. Furthermore, there was no significant decrease in progestin pharmacokinetic parameters during coadministration with an antibiotic.3 Study limitations included small sample sizes and the observational nature of the data.
How would you counsel this patient?
Available evidence suggests that nonrifamycin antibiotics do not diminish the effectiveness of the vaginal contraceptive ring or an oral hormonal contraceptive that contains at least 30 µg of ethinyl estradiol or 150 µg of levonorgestrel. Current guidelines do not recommend the use of additional backup contraception, regardless of hormonal contraception dose or formulation.4 Likewise, the most recent guidance for dental practitioners (ie, from 2012) no longer advises women to use additional contraceptive protection when taking nonrifamycin antibiotics.5
In our practice, we discuss the option of additional protection when prescribing formulations with lower estrogen doses (< 30 µg), not only because of the limitations of the available data, but also because of the high rates of unintended pregnancy with typical use of combined hormonal contraceptives (9% per year, unrelated to use of antibiotics).4 However, if our patient would rather not use additional barrier methods, she can be reassured that concomitant nonrifamycin antibiotic use is unlikely to affect contraceptive effectiveness.
HORMONE REPLACEMENT THERAPY IN CARRIERS OF THE BRCA1 MUTATION
A 41-year-old healthy mother of 3 was recently found to be a carrier of the BRCA1 mutation. She is planning to undergo prophylactic bilateral salpingo-oophorectomy for ovarian cancer prevention. However, she is apprehensive about undergoing surgical menopause. Should she be started on hormone replacement therapy after oophorectomy? How would hormone replacement therapy affect her risk of breast cancer?
In females who carry the BRCA1 mutation, the cumulative risk of both ovarian and breast cancer approaches 44% (95% confidence interval [CI] 36%–53%) and 72% (95% CI 65%–79%) by age 80.6 Prophylactic salpingo-oophorectomy reduces the risk of breast cancer by 50% and the risk of ovarian cancer by 90%. Unfortunately, premature withdrawal of ovarian hormones has been associated with long-term adverse effects including significant vasomotor symptoms, decreased quality of life, sexual dysfunction, early mortality, bone loss, decline in mood and cognition, and poor cardiovascular outcomes.7 Many of these effects can be avoided or lessened with hormone replacement therapy.
Kotsopoulos et al8 conducted a longitudinal, prospective analysis of BRCA1 mutation carriers in a multicenter study between 1995 and 2017. The mean follow-up period was 7.6 years (range 0.4–22.1). The study assessed associations between the use of hormone replacement therapy and breast cancer risk in carriers of the BRCA1 mutation who underwent prophylactic salpingo-oophorectomy. Study participants did not have a personal history of cancer. Those with a history of prophylactic mastectomy were excluded.
Participants completed a series of questionnaires every 2 years, disclosing updates in personal medical, cancer, and reproductive history. The questionnaires also inquired about the use of hormone replacement therapy, including the type used (estrogen only, progestin only, estrogen plus progestin, other), brand name, duration of use, and dose and route of administration (pill, patch, suppository).
Of the 13,087 BRCA1 mutation carriers identified, 872 met the study criteria. Of those, 377 (43%) reported using some form of hormone replacement therapy after salpingo-oophorectomy, and 495 (57%) did not. The average duration of use was 3.9 years (range 0.5–19), with most (69%) using estrogen alone; 18% used other regimens, including estrogen plus progestin and progestin only. A small percentage of participants did not indicate which formulation they used. On average, women using hormone replacement therapy underwent prophylactic oophorectomy earlier than nonusers (age 43.0 vs 48.4; absolute difference 5.5 years, P < .001).
During follow-up, there was no significant difference noted in the proportion of women diagnosed with breast cancer between hormone replacement therapy users and nonusers (10.3 vs 10.7%; absolute difference 0.4%; P = .86). In fact, for each year of estrogen-containing hormone replacement therapy, there was an 18% reduction in breast cancer risk when oophorectomy was performed before age 45 (95% CI 0.69–0.97). The authors also noted a nonsignificant 14% trend toward an increase in breast cancer risk for each year of progestin use after oophorectomy when surgery was performed before age 45 (95% CI 0.9–1.46).
Although prophylactic hysterectomy was not recommended, the authors noted that hysterectomy would eliminate the need for progestin-containing hormone replacement therapy. For those who underwent oophorectomy after age 45, hormone replacement therapy did not increase or decrease the risk of breast cancer.7
A meta-analysis by Marchetti et al9 also supports the safety of hormone replacement therapy after risk-reducing salpingo-oophorectomy. Three studies that included 1,100 patients were analyzed (including the Kotsopoulos study8 noted above). There was a nonsignificant decrease in breast cancer risk in women on estrogen-only hormone replacement therapy compared with women on estrogen-plus-progestin therapy (odds ratio 0.53, 95% CI 0.25–1.15). Overall, the authors regarded hormone replacement therapy as a safe therapeutic option after prophylactic salpingo-oophorectomy in carriers of the BRCA1 and BRCA2 mutations.9
In a case-control study published in 2016,10 hormone replacement therapy was assessed in 432 postmenopausal BRCA1 mutation carriers with invasive breast cancer (cases) and in 432 BRCA1 mutation carriers without a history of breast cancer (controls). Results showed no difference in breast cancer risk between hormone replacement therapy users and nonusers.10
Rebbeck et al11 evaluated short-term hormone replacement therapy in BRCA1 and BRCA2 gene-mutation carriers after they underwent prophylactic salpingo-oophorectomy. The results showed that hormone replacement did not affect the breast cancer risk-reduction conferred with prophylactic bilateral salpingo-oophorectomy.
Johansen et al12 evaluated hormone replacement therapy in premenopausal women after prophylactic salpingo-oophorectomy. They studied 324 carriers of BRCA gene mutations after they underwent prophylactic salpingo-oophorectomy and a subset of 950 controls who had bilateral salpingo-oophorectomy for reasons unrelated to cancer. In both groups, hormone replacement therapy was underutilized. The authors recommended using it when clinically indicated.
Should your patient start hormone replacement therapy?
This patient is healthy, and in the absence of contraindications, systemic hormone replacement therapy after prophylactic oophorectomy could mitigate the potential adverse effects of surgically induced menopause. The patient can be reassured that estrogen-containing short-term hormone replacement therapy is unlikely to increase her breast cancer risk.
HORMONAL CONTRACEPTION AND THE RISK OF BREAST CANCER
A 44-year-old woman presents to your office for an annual visit. She is sexually active but does not wish to become pregnant. She has a family history of breast cancer: her mother was diagnosed at age 53. She is interested in an oral contraceptive to prevent pregnancy and acne. However, she is nervous about being on any contraceptive that may increase her risk of breast cancer.
To date, studies assessing the effect of hormonal contraception on the risk of breast cancer have produced inconsistent results. Although most studies have shown no associated risk, a few have shown a temporary 20% to 30% increased risk of breast cancer during use.13,14 Case-controlled studies that reported an association between hormonal contraception and breast cancer included populations taking higher-dose combination pills, which are no longer prescribed. Most studies do not evaluate specific formulations of hormonal contraception, and little is known about effects associated with intrauterine devices or progestin-only contraception.
A prospective study performed by Mørch et al13 followed more than 1 million reproductive-aged women for a mean of 10.9 years. The Danish Cancer Registry was used to identify cases of invasive breast cancer. Women who used hormonal contraceptives had a relative risk of breast cancer of 1.20 compared with women not on hormonal contraception (95% CI 1.14–1.26). The study suggested that those who had been on contraceptive agents for more than 5 years had an increased risk and that this risk remained for 5 years after the agents were discontinued. Conversely, no increased risk of cancer was noted in those who used hormonal contraception for less than 5 years. No notable differences were seen among various formulations.
For women using the levonorgestrel-containing intrauterine device, the relative risk of breast cancer was 1.21 (95% CI 1.11–1.33). A few cancers were noted in those who used the progestin-only implant or those using depot medroxyprogesterone acetate. While the study showed an increased relative risk of breast cancer, the absolute risk was low—13 cases per 100,000, or approximately 1 additional case of breast cancer per 7,690 per year.13
This study had several important limitations. The authors did not adjust for common breast cancer risk factors including age at menarche, alcohol use, or breastfeeding. Additionally, the study did not account for the use of hormonal contraception before the study period and conversely, did not account for women who may have stopped taking their contraceptive despite their prescribed duration. The frequency of mammography was not explicitly noted, which could have shifted results for women who had more aggressive screening.
It is also noteworthy that the use of high-dose systemic progestins was not associated with an increased risk, whereas the levonorgestrel intrauterine device, which contains only 1/20th the dose of a low-dose oral contraceptive pill, was associated with an increased risk. This discrepancy in risk warrants further investigation, and clinicians should be aware that this inconsistency needs validation before changing clinical practice.
In an observational cohort study,15 more than 100,000 women ages 50 to 71 were followed prospectively for 15 years to evaluate the association between hormonal contraceptive use and the risk of gynecologic and breast cancers. In this study, the duration of hormonal contraceptive use, smoking status, alcohol use, body mass index, physical activity, and family history of cancer were recorded. Long-term hormonal contraceptive use reduced ovarian and endometrial cancer risks by 40% and 34%, respectively, with no increase in breast cancer risk regardless of family history.
How would you counsel the patient?
The patient should be educated on the benefits of hormonal contraception that extend beyond pregnancy prevention, including regulation of menses, improved acne, decreased risk of endometrial and ovarian cancer, and likely reductions in colorectal cancer and overall mortality risk.13–16 Further, after their own systematic review of the data assessing risk of breast cancer with hormonal contraception, the US Centers for Disease Control and Prevention state in their guidelines that all contraceptives may be used without limitation in those who have a family history of breast cancer.4 Any potential increased risk of breast cancer in women using hormonal contraception is small and would not outweigh the benefits associated with use.
One must consider the impact of an unintended pregnancy in such women, including effects on the health of the fetus and mother. Recent reports on the increasing rates of maternal death in the US (23.8 of 100,000 live births) serve as a reminder of the complications that can arise with pregnancy, especially if a mother’s health is not optimized before conception.17
MAMMOGRAPHY PLUS TOMOSYNTHESIS VS MAMMOGRAPHY ALONE
The same 44-year-old patient now inquires about screening for breast cancer. She is curious about 3-dimensional mammography and whether it would be a better screening test for her.
Digital breast tomosynthesis (DBT) is a newer imaging modality that provides a 3-dimensional reconstruction of the breast using low-dose x-ray imaging. Some studies have shown that combining DBT with digital mammography may be superior to digital mammography alone in detecting cancers.18 However, digital mammography is currently the gold standard for breast cancer screening and is the only test proven to reduce mortality.18,19
In a retrospective US study of 13 medical centers,20 breast cancer detection rates increased by 41% the year after DBT was introduced, from 2.9 to 4.1 per 1,000 cases. DBT was associated with 16 fewer patients recalled for repeat imaging out of 1,000 women screened (as opposed to mammography alone). Two European studies similarly suggested an increase in cancer detection with lower recall rates.21,22
Is 3-D mammography a better option?
In a 2-arm study by Pattacini et al,18 nearly 20,000 women ages 45 to 70 were randomized to undergo either digital mammography or digital mammography plus DBT for primary breast cancer screening. Women were enrolled over a 2-year period and were followed for 4.5 years, and the development of a primary invasive cancer was the primary end point. Recall rates, reading times, and radiation doses were also compared between the 2 groups.
Overall, the cancer detection rate was higher in the digital mammography plus DBT arm compared with digital mammography alone (8.6 vs 4.5 per 1,000). The detection rates were higher in the combined screening group among all age subgroups, with relative risks ranging from 1.83 to 2.04 (P = .93). The recall rate was 3.5% in the 2 arms, with relative risks ranging from 0.93 to 1.11 (P = .52). There was a reduction in the number of false positives seen in women undergoing digital mammography plus DBT when compared with digital mammography alone, from 30 per 1,000 to 27 per 1,000.
Detection of ductal carcinoma in situ increased in the experimental arm (relative detection 2.80, 95% CI 1.01–7.65) compared with invasive cancers. Comparing radiation, the dose was 2.3 times higher in those who underwent digital mammography plus DBT. The average reading times for digital mammography alone were 20 to 85 seconds; adding DBT added 35 to 81 seconds.19
Should you advise 3-D mammography?
The patient should be educated on the benefits of both digital mammography alone and digital mammography plus DBT. The use of digital mammography plus DBT has been supported in various studies and has been shown to increase cancer detection rates, although data are still conflicting regarding recall rates.19,20 More studies are needed to determine its effect on breast cancer morality.
Routine use of DBT in women with or without dense breast tissue has not been recommended by organizations such as the USPSTF and the American College of Obstetricians and Gynecologists.23,24 While there is an increased dose of radiation, it still falls below the US Food and Drug Administration limits and should not be the sole barrier to use.
- Cauley JA. Screening for osteoporosis. JAMA 2018; 319(24):2483–2485. doi:10.1001/jama.2018.5722
- US Preventive Services Task Force, Curry SJ, Krist AH, Owens DK, et al. Screening for osteoporosis to prevent fractures: US Preventive Services Task Force recommendation statement. JAMA 2018; 319(24):2521–2531. doi:10.1001/jama.2018.7498
- Simmons KB, Haddad LB, Nanda K, Curtis KM. Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review. Am J Obstet Gynecol 2018; 218(1):88–97.e14. doi:10.1016/j.ajog.2017.07.003
- Curtis KM, Tepper NK, Jatlaoui TC, et al. US Medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep 2016; 65(3):1–103. doi:10.15585/mmwr.rr6503a1
- Taylor J, Pemberton MN. Antibiotics and oral contraceptives: new considerations for dental practice. Br Dent J 2012; 212(10):481–483. doi:10.1038/sj.bdj.2012.414
- Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 2017; 317(23):2402–2416. doi:10.1001/jama.2017.7112
- Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long-term health consequences of premature or early menopause and considerations for management. Climacteric 2015; 18(4):483–491. doi:10.3109/13697137.2015.1020484
- Kotsopoulos J, Gronwald J, Karlan BY, et al; Hereditary Breast Cancer Clinical Study Group. Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. JAMA Oncol 2018; 4(8):1059–1065. doi:10.1001/jamaoncol.2018.0211
- Marchetti C, De Felice F, Boccia S, et al. Hormone replacement therapy after prophylactic risk reducing salpingo-oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a meta-analysis. Crit Rev Oncol Hematol 2018; 132:111–115. doi:10.1016/j.critrevonc.2018.09.018
- Kotsopoulos J, Huzarski T, Gronwald J, et al. Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case-control study. Breast Cancer Res Treat 2016; 155(2):365–373. doi:10.1007/s10549-016-3685-3
- Rebbeck TR, Friebel T, Wagner T, et al; PROSE Study Group. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2005; 23(31):7804–7810. doi:10.1200/JCO.2004.00.8151
- Johansen N, Liavaag AH, Iversen OE, Dørum A, Braaten T, Michelsen TM. Use of hormone replacement therapy after risk-reducing salpingo-oophorectomy. Acta Obstet Gynecol Scand 2017; 96(5):547–555. doi:10.1111/aogs.13120
- Mørch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard Ø. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med 2017; 377(23):2228–2239. doi:10.1056/NEJMoa1700732
- Batur P, Sikka S, McNamara M. Contraception update: extended use of long acting methods, hormonal contraception risks, and over the counter access. J Womens Health (Larchmt) 2018. doi:10.1089/jwh.2018.7391. [Epub ahead of print]
- Michels KA, Pfeiffer RM, Brinton LA, Trabert B. Modification of the associations between duration of oral contraceptive use and ovarian, endometrial, breast, and colorectal cancers. JAMA Oncol 2018; 4(4):516–521. doi:10.1001/jamaoncol.2017.4942
- Iversen L, Fielding S, Lidegaard Ø, Mørch LS, Skovlund CW, Hannaford PC. Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study. BMJ 2018; 362:k3609. doi:10.1136/bmj.k3609
- MacDorman MF, Declercq E, Cabral H, Morton C. Recent increases in the US maternal mortality rate: disentangling trends from measurement issues. Obstet Gynecol 2016; 128(3):447–455. doi:10.1097/AOG.0000000000001556
- Pattacini P, Nitrosi A, Giorgi Rossi P, et al; RETomo Working Group. Digital mammography versus digital mammography plus tomosynthesis for breast cancer screening: the Reggio Emilia tomosynthesis randomized trial. Radiology 2018; 288(2):375–385. doi:10.1148/radiol.2018172119
- Pace L, Keating NL. A systematic assessment of benefits and risks to guide breast cancer screening decisions. JAMA 2014; 311(13):1327–1335. doi:10.1001/jama.2014.1398
- Friedewald SM, Rafferty EA, Rose SL, et al. Breast cancer screening using tomosynthesis in combination with digital mammography. JAMA 2014; 311(24):2499–2507. doi:10.1001/jama.2014.6095
- Skaane P, Bandos AI, Gullien R, et al. Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program. Radiology 2013; 267(1):47–56. doi:10.1148/radiol.12121373
- Ciatto S, Houssami N, Bernardi D, et al. Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study. Lancet Oncol 2013; 14(7):583–589. doi:10.1016/S1470-2045(13)70134-7
- US Preventive Services Task Force. Final recommendation statement: breast cancer: screening. www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/breast-cancer-screening1. Accessed May 13, 2019.
- American College of Obstetricians and Gynecologists. Breast cancer risk assessment and screening in average-risk women. www.acog.org/Clinical-Guidance-and-Publications/Practice-Bulletins/Committee-on-Practice-Bulletins-Gynecology/Breast-Cancer-Risk-Assessment-and-Screening-in-Average-Risk-Women?IsMobileSet=false#5. Accessed May 13, 2019.
- Cauley JA. Screening for osteoporosis. JAMA 2018; 319(24):2483–2485. doi:10.1001/jama.2018.5722
- US Preventive Services Task Force, Curry SJ, Krist AH, Owens DK, et al. Screening for osteoporosis to prevent fractures: US Preventive Services Task Force recommendation statement. JAMA 2018; 319(24):2521–2531. doi:10.1001/jama.2018.7498
- Simmons KB, Haddad LB, Nanda K, Curtis KM. Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review. Am J Obstet Gynecol 2018; 218(1):88–97.e14. doi:10.1016/j.ajog.2017.07.003
- Curtis KM, Tepper NK, Jatlaoui TC, et al. US Medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep 2016; 65(3):1–103. doi:10.15585/mmwr.rr6503a1
- Taylor J, Pemberton MN. Antibiotics and oral contraceptives: new considerations for dental practice. Br Dent J 2012; 212(10):481–483. doi:10.1038/sj.bdj.2012.414
- Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 2017; 317(23):2402–2416. doi:10.1001/jama.2017.7112
- Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long-term health consequences of premature or early menopause and considerations for management. Climacteric 2015; 18(4):483–491. doi:10.3109/13697137.2015.1020484
- Kotsopoulos J, Gronwald J, Karlan BY, et al; Hereditary Breast Cancer Clinical Study Group. Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. JAMA Oncol 2018; 4(8):1059–1065. doi:10.1001/jamaoncol.2018.0211
- Marchetti C, De Felice F, Boccia S, et al. Hormone replacement therapy after prophylactic risk reducing salpingo-oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a meta-analysis. Crit Rev Oncol Hematol 2018; 132:111–115. doi:10.1016/j.critrevonc.2018.09.018
- Kotsopoulos J, Huzarski T, Gronwald J, et al. Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case-control study. Breast Cancer Res Treat 2016; 155(2):365–373. doi:10.1007/s10549-016-3685-3
- Rebbeck TR, Friebel T, Wagner T, et al; PROSE Study Group. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2005; 23(31):7804–7810. doi:10.1200/JCO.2004.00.8151
- Johansen N, Liavaag AH, Iversen OE, Dørum A, Braaten T, Michelsen TM. Use of hormone replacement therapy after risk-reducing salpingo-oophorectomy. Acta Obstet Gynecol Scand 2017; 96(5):547–555. doi:10.1111/aogs.13120
- Mørch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard Ø. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med 2017; 377(23):2228–2239. doi:10.1056/NEJMoa1700732
- Batur P, Sikka S, McNamara M. Contraception update: extended use of long acting methods, hormonal contraception risks, and over the counter access. J Womens Health (Larchmt) 2018. doi:10.1089/jwh.2018.7391. [Epub ahead of print]
- Michels KA, Pfeiffer RM, Brinton LA, Trabert B. Modification of the associations between duration of oral contraceptive use and ovarian, endometrial, breast, and colorectal cancers. JAMA Oncol 2018; 4(4):516–521. doi:10.1001/jamaoncol.2017.4942
- Iversen L, Fielding S, Lidegaard Ø, Mørch LS, Skovlund CW, Hannaford PC. Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study. BMJ 2018; 362:k3609. doi:10.1136/bmj.k3609
- MacDorman MF, Declercq E, Cabral H, Morton C. Recent increases in the US maternal mortality rate: disentangling trends from measurement issues. Obstet Gynecol 2016; 128(3):447–455. doi:10.1097/AOG.0000000000001556
- Pattacini P, Nitrosi A, Giorgi Rossi P, et al; RETomo Working Group. Digital mammography versus digital mammography plus tomosynthesis for breast cancer screening: the Reggio Emilia tomosynthesis randomized trial. Radiology 2018; 288(2):375–385. doi:10.1148/radiol.2018172119
- Pace L, Keating NL. A systematic assessment of benefits and risks to guide breast cancer screening decisions. JAMA 2014; 311(13):1327–1335. doi:10.1001/jama.2014.1398
- Friedewald SM, Rafferty EA, Rose SL, et al. Breast cancer screening using tomosynthesis in combination with digital mammography. JAMA 2014; 311(24):2499–2507. doi:10.1001/jama.2014.6095
- Skaane P, Bandos AI, Gullien R, et al. Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program. Radiology 2013; 267(1):47–56. doi:10.1148/radiol.12121373
- Ciatto S, Houssami N, Bernardi D, et al. Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study. Lancet Oncol 2013; 14(7):583–589. doi:10.1016/S1470-2045(13)70134-7
- US Preventive Services Task Force. Final recommendation statement: breast cancer: screening. www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/breast-cancer-screening1. Accessed May 13, 2019.
- American College of Obstetricians and Gynecologists. Breast cancer risk assessment and screening in average-risk women. www.acog.org/Clinical-Guidance-and-Publications/Practice-Bulletins/Committee-on-Practice-Bulletins-Gynecology/Breast-Cancer-Risk-Assessment-and-Screening-in-Average-Risk-Women?IsMobileSet=false#5. Accessed May 13, 2019.
KEY POINTS
- The US Preventive Services Task Force recommends screening bone density when the 10-year risk of major osteoporotic fracture is more than 8.4%.
- Women can be reassured that nonrifamycin antibiotics are unlikely to reduce efficacy of hormonal contraception.
- Hormone replacement therapy after prophylactic bilateral salpingo-oophorectomy does not increase breast cancer risk in women who carry the BRCA1 gene mutation.
- Hormonal contraception may increase the risk of breast cancer by 1 extra case per 7,690 women, although most studies suggest there is no increased risk.
- The use of digital breast tomosynthesis along with digital mammography can increase cancer detection in women with dense breast tissue, but it is not yet routinely recommended by most professional societies.
Click for Credit: Biomarkers for VTE risk; Exercise & concussion recovery; more
Here are 5 articles from the June issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Expert: There’s no single treatment for fibromyalgia
To take the posttest, go to: https://bit.ly/2EAI5v1
Expires February 3, 2020
2. Mood and behavior are different targets for irritability in children
To take the posttest, go to: https://bit.ly/2wpLS9X
Expires February 6, 2020
3. Biomarkers predict VTE risk with menopausal oral hormone therapy
To take the posttest, go to: https://bit.ly/2JKEQFC
Expires February 6, 2020
4. Mild aerobic exercise speeds sports concussion recovery
To take the posttest, go to: https://bit.ly/30RuYiE
Expires February 4, 2020
5. For CABG, multiple and single arterial grafts show no survival difference
To take the posttest, go to: https://bit.ly/2wtiCiF
Expires January 31, 2020
Here are 5 articles from the June issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Expert: There’s no single treatment for fibromyalgia
To take the posttest, go to: https://bit.ly/2EAI5v1
Expires February 3, 2020
2. Mood and behavior are different targets for irritability in children
To take the posttest, go to: https://bit.ly/2wpLS9X
Expires February 6, 2020
3. Biomarkers predict VTE risk with menopausal oral hormone therapy
To take the posttest, go to: https://bit.ly/2JKEQFC
Expires February 6, 2020
4. Mild aerobic exercise speeds sports concussion recovery
To take the posttest, go to: https://bit.ly/30RuYiE
Expires February 4, 2020
5. For CABG, multiple and single arterial grafts show no survival difference
To take the posttest, go to: https://bit.ly/2wtiCiF
Expires January 31, 2020
Here are 5 articles from the June issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Expert: There’s no single treatment for fibromyalgia
To take the posttest, go to: https://bit.ly/2EAI5v1
Expires February 3, 2020
2. Mood and behavior are different targets for irritability in children
To take the posttest, go to: https://bit.ly/2wpLS9X
Expires February 6, 2020
3. Biomarkers predict VTE risk with menopausal oral hormone therapy
To take the posttest, go to: https://bit.ly/2JKEQFC
Expires February 6, 2020
4. Mild aerobic exercise speeds sports concussion recovery
To take the posttest, go to: https://bit.ly/30RuYiE
Expires February 4, 2020
5. For CABG, multiple and single arterial grafts show no survival difference
To take the posttest, go to: https://bit.ly/2wtiCiF
Expires January 31, 2020
Obesity doesn’t hamper flu vaccine response in pregnancy
LJUBLJANA, SLOVENIA – ; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m2 or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.
Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.
Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.
Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.
LJUBLJANA, SLOVENIA – ; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m2 or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.
Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.
Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.
Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.
LJUBLJANA, SLOVENIA – ; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m2 or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.
Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.
Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.
Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.
REPORTING FROM ESPID 2019
Key clinical point: High BMI doesn’t impair influenza vaccine responses in pregnant women.
Major finding: Protective antibody levels against all three vaccine antigens were documented 1 month post vaccination in 92% of the obese and 74% of the nonobese mothers.
Study details: This was a prospective observational study of 90 women vaccinated against influenza during pregnancy, 24 of whom were obese.
Disclosures: The study was supported by the University of Adelaide Women’s and Children’s Hospital Research Foundation.