Breast Cancer

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

A new follow-up study of menopausal hormone therapy found that prior use of conjugated equine estrogen (CEE) decreased both breast cancer incidence and mortality, while prior use of CEE plus medroxyprogesterone acetate (MPA) was associated with an increase in incidence.

“Prior use of CEE alone is, to our knowledge, the first pharmacologic intervention demonstrated to be associated with a statistically significantly reduction in deaths from breast cancer,” wrote Rowan T. Chlebowski, MD, PhD, of the Lundquist Institute for Biomedical Innovation in Torrance, Calif., and his coauthors. The study was published July 28 in JAMA.

To further investigate the outcomes of the Women’s Health Initiative in regard to hormone therapy and breast cancer risk, the researchers analyzed the long-term follow-up of two randomized trials that included 27,347 postmenopausal women with no prior breast cancer and negative mammograms at baseline. Their mean (SD) age was 63.4 (7.2) years. Enrollment took place from 1993 to 1998; participants were contacted for follow-up every 6 months through 2005 and annually from then on. Mortality data were gathered from follow-up and the National Death Index.

The first trial included 16,608 women with a uterus. Among these women, 8,506 received 0.625 mg/day of CEE plus 2.5 mg/day of MPA, and 8,102 received placebo. The second trial included 10,739 women who’d gotten a hysterectomy, 5,310 of whom received 0.625 mg/day of CEE alone and 5,429 of whom received placebo. The first trial ended in 2002 after a median intervention period of 5.6 years, and the second trial ended in 2004 after a period of 7.2 years.

An analysis in 2015 found that CEE alone was associated with lower risk of breast cancer and CEE plus MPA was associated with increased risk.

The current analysis confirmed that, after a median of 20.3 years of follow-up, and with mortality data now available for more than 98% of participants, CEE alone was associated with fewer cases of breast cancer (238 cases, annualized rate 0.30%), compared with placebo (296 cases, annualized rate 0.37%; hazard ratio 0.78; 95% confidence interval, 0.65-0.93; P = .005).

Furthermore, CEE alone was also associated with lower mortality (30 deaths, annualized mortality rate 0.031%), compared with placebo (46 deaths, annualized mortality rate 0.046%; HR 0.60; 95% CI, 0.37-0.97; P = .04).

By comparison, CEE plus MPA was linked with more cases of breast cancer (584 cases, annualized rate 0.45%) than placebo (447 cases, annualized rate 0.36%; HR 1.28; 95% CI, 1.13-1.45; P < .001). In regard to mortality, there was no statistically significant difference between CEE plus MPA (71 deaths, annualized mortality rate 0.045%) and placebo (53 deaths, annualized mortality rate 0.035%; HR 1.35; 95% CI, 0.94-1.95; P = .11).

“The big thing to think about is estrogen alone reducing breast cancer mortality by 40%,” said Dr. Chlebowski in an interview. “None of the other interventions, including tamoxifen, had any change on mortality. This should change the way we look at breast cancer prevention, though we might have to be a little creative about it. I think you have to be a little away from menopause for it to reduce breast cancer. But we wanted to start that debate.

“On the other hand,” he said, “a woman takes estrogen plus progestin and when you look at that curve, it’s staying about 25% increased. You take it for 5.6 years and the increase continues through 20 years, so you’re maybe buying a lifetime of increase in breast cancer by taking estrogen plus progestin for 5 years.”

He also highlighted the comprehensiveness of the mortality data, noting that “when you hook up to the National Death Index, they find 98% of all deaths in the United States. That’s really remarkable; you retain the whole power of the randomization. It means our data, between the death index and our follow-up of participants, is essentially complete.”

Use of hormone therapy, and decoding the outcomes, remains ‘complex’

Decades after the data were gathered from the Women’s Health Initiative clinical trials, they continue to assist researchers and patients alike, wrote Christina A. Minami, MD, of Brigham and Women’s Hospital in Boston and Rachel A. Freedman, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

That said, in regard to the findings of this latest analysis, “many questions still remain on whether (and how) a hormone therapy intervention that occurred many years earlier may continue to affect breast cancer risk and mortality at 20 years,” they wrote. They noted that it’s “impossible” to isolate how exposure to certain therapies can impact long-term outcomes, and that a high percentage of patients who discontinued the drugs during each trial muddy the waters even further.

“Decisions to initiate these medications remain complex,” they added, emphasizing that breast cancer risk is just one of many factors that physicians must consider when considering hormone therapy for their patients.

Dr. Chlebowski and his coauthors acknowledged their study’s limitations, including the use of very specifically administered and formulated dosages making their findings “not necessarily generalizable to other preparations.” In addition, they noted the significant percentage of patients – 54% with CEE alone and 42% with CEE plus MPA – who discontinued drug usage during their respective trials.

The Women’s Health Initiative is supported by the National Institutes of Health and the Department of Health and Human Services. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various government organizations, foundations, and pharmaceutical companies. The editorial’s authors reported no conflicts of interest.

SOURCE: Chlebowski RT et al. JAMA. 2020 Jul 28. doi: 10.1001/jama.2020.9482.

A new follow-up study of menopausal hormone therapy found that prior use of conjugated equine estrogen (CEE) decreased both breast cancer incidence and mortality, while prior use of CEE plus medroxyprogesterone acetate (MPA) was associated with an increase in incidence.

“Prior use of CEE alone is, to our knowledge, the first pharmacologic intervention demonstrated to be associated with a statistically significantly reduction in deaths from breast cancer,” wrote Rowan T. Chlebowski, MD, PhD, of the Lundquist Institute for Biomedical Innovation in Torrance, Calif., and his coauthors. The study was published July 28 in JAMA.

To further investigate the outcomes of the Women’s Health Initiative in regard to hormone therapy and breast cancer risk, the researchers analyzed the long-term follow-up of two randomized trials that included 27,347 postmenopausal women with no prior breast cancer and negative mammograms at baseline. Their mean (SD) age was 63.4 (7.2) years. Enrollment took place from 1993 to 1998; participants were contacted for follow-up every 6 months through 2005 and annually from then on. Mortality data were gathered from follow-up and the National Death Index.

The first trial included 16,608 women with a uterus. Among these women, 8,506 received 0.625 mg/day of CEE plus 2.5 mg/day of MPA, and 8,102 received placebo. The second trial included 10,739 women who’d gotten a hysterectomy, 5,310 of whom received 0.625 mg/day of CEE alone and 5,429 of whom received placebo. The first trial ended in 2002 after a median intervention period of 5.6 years, and the second trial ended in 2004 after a period of 7.2 years.

An analysis in 2015 found that CEE alone was associated with lower risk of breast cancer and CEE plus MPA was associated with increased risk.

The current analysis confirmed that, after a median of 20.3 years of follow-up, and with mortality data now available for more than 98% of participants, CEE alone was associated with fewer cases of breast cancer (238 cases, annualized rate 0.30%), compared with placebo (296 cases, annualized rate 0.37%; hazard ratio 0.78; 95% confidence interval, 0.65-0.93; P = .005).

Furthermore, CEE alone was also associated with lower mortality (30 deaths, annualized mortality rate 0.031%), compared with placebo (46 deaths, annualized mortality rate 0.046%; HR 0.60; 95% CI, 0.37-0.97; P = .04).

By comparison, CEE plus MPA was linked with more cases of breast cancer (584 cases, annualized rate 0.45%) than placebo (447 cases, annualized rate 0.36%; HR 1.28; 95% CI, 1.13-1.45; P < .001). In regard to mortality, there was no statistically significant difference between CEE plus MPA (71 deaths, annualized mortality rate 0.045%) and placebo (53 deaths, annualized mortality rate 0.035%; HR 1.35; 95% CI, 0.94-1.95; P = .11).

“The big thing to think about is estrogen alone reducing breast cancer mortality by 40%,” said Dr. Chlebowski in an interview. “None of the other interventions, including tamoxifen, had any change on mortality. This should change the way we look at breast cancer prevention, though we might have to be a little creative about it. I think you have to be a little away from menopause for it to reduce breast cancer. But we wanted to start that debate.

“On the other hand,” he said, “a woman takes estrogen plus progestin and when you look at that curve, it’s staying about 25% increased. You take it for 5.6 years and the increase continues through 20 years, so you’re maybe buying a lifetime of increase in breast cancer by taking estrogen plus progestin for 5 years.”

He also highlighted the comprehensiveness of the mortality data, noting that “when you hook up to the National Death Index, they find 98% of all deaths in the United States. That’s really remarkable; you retain the whole power of the randomization. It means our data, between the death index and our follow-up of participants, is essentially complete.”

Use of hormone therapy, and decoding the outcomes, remains ‘complex’

Decades after the data were gathered from the Women’s Health Initiative clinical trials, they continue to assist researchers and patients alike, wrote Christina A. Minami, MD, of Brigham and Women’s Hospital in Boston and Rachel A. Freedman, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

That said, in regard to the findings of this latest analysis, “many questions still remain on whether (and how) a hormone therapy intervention that occurred many years earlier may continue to affect breast cancer risk and mortality at 20 years,” they wrote. They noted that it’s “impossible” to isolate how exposure to certain therapies can impact long-term outcomes, and that a high percentage of patients who discontinued the drugs during each trial muddy the waters even further.

“Decisions to initiate these medications remain complex,” they added, emphasizing that breast cancer risk is just one of many factors that physicians must consider when considering hormone therapy for their patients.

Dr. Chlebowski and his coauthors acknowledged their study’s limitations, including the use of very specifically administered and formulated dosages making their findings “not necessarily generalizable to other preparations.” In addition, they noted the significant percentage of patients – 54% with CEE alone and 42% with CEE plus MPA – who discontinued drug usage during their respective trials.

The Women’s Health Initiative is supported by the National Institutes of Health and the Department of Health and Human Services. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various government organizations, foundations, and pharmaceutical companies. The editorial’s authors reported no conflicts of interest.

SOURCE: Chlebowski RT et al. JAMA. 2020 Jul 28. doi: 10.1001/jama.2020.9482.

A new follow-up study of menopausal hormone therapy found that prior use of conjugated equine estrogen (CEE) decreased both breast cancer incidence and mortality, while prior use of CEE plus medroxyprogesterone acetate (MPA) was associated with an increase in incidence.

“Prior use of CEE alone is, to our knowledge, the first pharmacologic intervention demonstrated to be associated with a statistically significantly reduction in deaths from breast cancer,” wrote Rowan T. Chlebowski, MD, PhD, of the Lundquist Institute for Biomedical Innovation in Torrance, Calif., and his coauthors. The study was published July 28 in JAMA.

To further investigate the outcomes of the Women’s Health Initiative in regard to hormone therapy and breast cancer risk, the researchers analyzed the long-term follow-up of two randomized trials that included 27,347 postmenopausal women with no prior breast cancer and negative mammograms at baseline. Their mean (SD) age was 63.4 (7.2) years. Enrollment took place from 1993 to 1998; participants were contacted for follow-up every 6 months through 2005 and annually from then on. Mortality data were gathered from follow-up and the National Death Index.

The first trial included 16,608 women with a uterus. Among these women, 8,506 received 0.625 mg/day of CEE plus 2.5 mg/day of MPA, and 8,102 received placebo. The second trial included 10,739 women who’d gotten a hysterectomy, 5,310 of whom received 0.625 mg/day of CEE alone and 5,429 of whom received placebo. The first trial ended in 2002 after a median intervention period of 5.6 years, and the second trial ended in 2004 after a period of 7.2 years.

An analysis in 2015 found that CEE alone was associated with lower risk of breast cancer and CEE plus MPA was associated with increased risk.

The current analysis confirmed that, after a median of 20.3 years of follow-up, and with mortality data now available for more than 98% of participants, CEE alone was associated with fewer cases of breast cancer (238 cases, annualized rate 0.30%), compared with placebo (296 cases, annualized rate 0.37%; hazard ratio 0.78; 95% confidence interval, 0.65-0.93; P = .005).

Furthermore, CEE alone was also associated with lower mortality (30 deaths, annualized mortality rate 0.031%), compared with placebo (46 deaths, annualized mortality rate 0.046%; HR 0.60; 95% CI, 0.37-0.97; P = .04).

By comparison, CEE plus MPA was linked with more cases of breast cancer (584 cases, annualized rate 0.45%) than placebo (447 cases, annualized rate 0.36%; HR 1.28; 95% CI, 1.13-1.45; P < .001). In regard to mortality, there was no statistically significant difference between CEE plus MPA (71 deaths, annualized mortality rate 0.045%) and placebo (53 deaths, annualized mortality rate 0.035%; HR 1.35; 95% CI, 0.94-1.95; P = .11).

“The big thing to think about is estrogen alone reducing breast cancer mortality by 40%,” said Dr. Chlebowski in an interview. “None of the other interventions, including tamoxifen, had any change on mortality. This should change the way we look at breast cancer prevention, though we might have to be a little creative about it. I think you have to be a little away from menopause for it to reduce breast cancer. But we wanted to start that debate.

“On the other hand,” he said, “a woman takes estrogen plus progestin and when you look at that curve, it’s staying about 25% increased. You take it for 5.6 years and the increase continues through 20 years, so you’re maybe buying a lifetime of increase in breast cancer by taking estrogen plus progestin for 5 years.”

He also highlighted the comprehensiveness of the mortality data, noting that “when you hook up to the National Death Index, they find 98% of all deaths in the United States. That’s really remarkable; you retain the whole power of the randomization. It means our data, between the death index and our follow-up of participants, is essentially complete.”

Use of hormone therapy, and decoding the outcomes, remains ‘complex’

Decades after the data were gathered from the Women’s Health Initiative clinical trials, they continue to assist researchers and patients alike, wrote Christina A. Minami, MD, of Brigham and Women’s Hospital in Boston and Rachel A. Freedman, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

That said, in regard to the findings of this latest analysis, “many questions still remain on whether (and how) a hormone therapy intervention that occurred many years earlier may continue to affect breast cancer risk and mortality at 20 years,” they wrote. They noted that it’s “impossible” to isolate how exposure to certain therapies can impact long-term outcomes, and that a high percentage of patients who discontinued the drugs during each trial muddy the waters even further.

“Decisions to initiate these medications remain complex,” they added, emphasizing that breast cancer risk is just one of many factors that physicians must consider when considering hormone therapy for their patients.

Dr. Chlebowski and his coauthors acknowledged their study’s limitations, including the use of very specifically administered and formulated dosages making their findings “not necessarily generalizable to other preparations.” In addition, they noted the significant percentage of patients – 54% with CEE alone and 42% with CEE plus MPA – who discontinued drug usage during their respective trials.

The Women’s Health Initiative is supported by the National Institutes of Health and the Department of Health and Human Services. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various government organizations, foundations, and pharmaceutical companies. The editorial’s authors reported no conflicts of interest.

SOURCE: Chlebowski RT et al. JAMA. 2020 Jul 28. doi: 10.1001/jama.2020.9482.

A study has shown for the first time that knowing BRCA1/2 mutation status before a breast cancer diagnosis was associated with better survival.

The study, conducted among Ashkenazi Jewish women in Israel, showed that among women who knew their carrier status before they developed breast cancer, diagnoses were made at an earlier disease stage and 5-year survival was improved compared to women who learned their carrier status only after their disease had been diagnosed.

The study was published online on July 9 in JAMA Oncology.

“I don’t want to belittle the complexities of knowing that you’re a carrier. But I think these results really show that knowledge is power,” first author Ephrat Levy-Lahad, MD, director of the medical genetics unit at Shaare Zedek Medical Center in Jerusalem, Israel, told Medscape Medical News.

Carrying a BRCA1/2 pathogenic mutation is associated with a 70% to 80% lifetime risk for breast cancer and about a 10% to 50% lifetime risk for ovarian cancer, depending on the specific mutation. Only about 10% of carriers will not develop either cancer during their lifetime.

The study provides support for genetic screening for pathogenic BRCA1/2 mutations, especially in high-risk populations, according to Levy-Lahad.

“For me, the results are part of a bigger picture.... I think we should be moving towards general population screening, certainly in high-risk populations like Ashkenazi Jews,” she said.

In Israel, that decision has already been made: a new policy, introduced in January 2020, offers testing for common BRCA1/2 mutations for all Ashkenazi Jewish women.

However, women in other countries may also benefit from testing, she argues. About half of BRCA1/2 carriers in a general population like that of the United States do not have a family history that would indicate a need for testing. That means many women who carry these mutations may not be taking advantage of recommended surveillance and prevention measures, she said.

But screening for BRCA1/2 mutations becomes more complicated when applied to more general populations, she acknowledged.

About 2.5% of women of Ashkenazi Jewish descent carry pathogenic mutations for BRCA1/2, compared to 0.5% in the general White population.

Also, screening in the Ashkenazi Jewish population is probably simpler than in the general population. Just three mutations are definitely known to cause disease and need to be tested for among Ashkenazi Jews. Screening in a larger population would require full sequencing of the gene. That increases the likelihood of finding variants of unknown significance (VUSs), which muddies the water. Knowledge is incomplete about whether some of these VUSs increase cancer risk, and physicians do not always know how to manage them in women who test positive.

Moreover, Israel has a national health system. Screening in a country without universal health insurance such as the United States raises questions about whether follow-up would be covered by insurance carriers for women who test positive.

Mehmet Copur, MD, an oncologist at Morrison Cancer Center in Hastings, Nebraska, questions how general population screening could be done in “real life.”

“These findings should be taken into consideration in the context of the patient population who would agree to genetic testing, who would agree to comply with the recommended guidelines for risk reduction, and who would have insurance coverage or resources to comply with the recommendations,” Copur told Medscape Medical News.

“If BRCA-positive patients did not or could not follow these recommendations, the results would different,” he added.

The most crucial component of screening for these mutations is genetic counselors, who are in short supply in the United States, according to Copur.

Another issue is that of cost. Genetic counseling is not always covered by insurance, especially for individuals who do not have a family history of BRCA-related cancers. Genetic testing is not cheap, and the costs of monitoring women who test positive could be prohibitive, especially in a healthcare system burdened by COVID-19.

“Whether our current healthcare system could bear the cost of such a change is up for debate. The screening itself may be feasible, but offering lifelong surveillance to every woman identified with mutations could present huge capacity issues,” Copur said. “Maybe in the future, the healthcare system can be ready for such an undertaking, but I don’t think we are there yet.”

Although she acknowledges the differences in risk between Ashkenazi Jews and the general population, Levy-Lahad thinks not having screening is like “throwing the baby out with the bath water.”

“Maybe we’re not ready for total general population screening, but I think we have to start thinking along those lines,” she said. “We have this incredible tool for cancer prevention, and we should really be using it, certainly in populations like Ashkenazi Jews.”

Researchers conducted a retrospective analysis that included 105 women diagnosed with breast cancer at Shaare Zedek Medical Center in Jerusalem between 2005 and 2016. Forty-two women knew they were carriers before their breast cancer diagnosis, and 63 learned of their carrier status only after diagnosis. Of the participants, 83% were Ashkenazi Jews. For both prediagnosis and postdiagnosis groups, the age at diagnosis was the same (50.4 years). For both groups, distributions of pathogenic mutations were similar. There were no significant differences in hormone receptor or ERBB2 status.

Among women who knew they were carriers before diagnosis, 80.9% (34/42) were diagnosed either with ductal carcinoma in situ or stage 1 disease. Only 9.5% (4/42) of these women were diagnosed with disease of stage 2 or higher.

In comparison, among women who learned their carrier status after diagnosis, 30% (19/63) had early-stage disease at diagnosis, and 52.4% (33/63) were diagnosed at stage 2 or higher (P < .001).

Compared to women who knew their carrier status before diagnosis, women who found out after diagnosis had 12 times higher odds of being diagnosed with disease of advanced clinical stage (P = .001) and eight times higher odds of being diagnosed with disease of advanced pathologic stage (P = .002).

A sentinel node biopsy was sufficient in 85.7% (36/42) of women who knew their carrier status before diagnosis; 7.2% (3/42) of these women needed a full lymph node dissection. In contrast, 3.2% (2/63) of women who learned their carrier status after diagnosis underwent sentinel node biopsy, and 34.9% (25/105) needed a full lymph node dissection (P < .001).

Among women who knew their carrier status before diagnosis, 54.8% (23/42) did not need chemotherapy at all, and none needed neoadjuvant chemotherapy. Only 4.8% (3/63) of women who learned their mutation status after diagnosis were able to forgo chemotherapy (P < .001); 22.2% (14/63) needed neoadjuvant therapy (P = .001).

These findings appeared to translate into better outcomes. Overall 5-year survival was significantly higher among women who knew their carrier status before diagnosis compared to women who found out afterward (94% [SE 4%] vs 78% [SE 5%]; P = .03). Only two of 42 women (4.8%) in the prediagnosis group died, compared to 16 of 63 (25.4%) in the postdiagnosis group.

Analyses that controlled for year at diagnosis showed that women who learned their carrier status before diagnosis had significantly lower risk for overall mortality compared with those who found out after diagnosis (hazard ratio [HR], 0.20; 95% CI, 0.04 – 0.93; P = .04). However, these results lost significance when controlled for age, socioeconomic index, family history, and gene variant (HR, 0.16; 95% CI, 0.02 – 1.4; P = .10).

Higher socioeconomic status (HR, 0.76; 95% CI, 0.6 – 0.97; P = .03), gene variant (BRCA2 vs BRCA1: HR, 0.15; 95% CI, 0.03 – 0.75; P = .02), and age at diagnosis (HR, 1.047; 95% CI, 1.003 – 1.093; P = .04) were all associated with overall mortality.

“I can’t infer causation, but we suspect that the reason for these results is the difference in follow-up,” Levy-Lahad said.

Most of the women (95.2%, 40/42) who knew their carrier status before diagnosis received their follow-up at the medical center’s high-risk carrier clinic. Twenty-seven of 42 (64.3%) of these women were diagnosed with breast MRI. By contrast, only 1.6% (1/63) of women who found out their carrier status after diagnosis were diagnosed with breast MRI. Breast MRI is not routinely used for breast cancer screening but can be more sensitive than mammography for detecting breast cancer.

The study was funded by the Breast Cancer Research Foundation and by a gift from Ellie and David Werber to ShaareZedek Medical Center.

Levy-Lahad received grants from the Breast Cancer Research Foundation and from the Israel Cancer Association during the conduct of the study and personal fees from AstraZeneca outside the submitted work. Copur has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A study has shown for the first time that knowing BRCA1/2 mutation status before a breast cancer diagnosis was associated with better survival.

The study, conducted among Ashkenazi Jewish women in Israel, showed that among women who knew their carrier status before they developed breast cancer, diagnoses were made at an earlier disease stage and 5-year survival was improved compared to women who learned their carrier status only after their disease had been diagnosed.

The study was published online on July 9 in JAMA Oncology.

“I don’t want to belittle the complexities of knowing that you’re a carrier. But I think these results really show that knowledge is power,” first author Ephrat Levy-Lahad, MD, director of the medical genetics unit at Shaare Zedek Medical Center in Jerusalem, Israel, told Medscape Medical News.

Carrying a BRCA1/2 pathogenic mutation is associated with a 70% to 80% lifetime risk for breast cancer and about a 10% to 50% lifetime risk for ovarian cancer, depending on the specific mutation. Only about 10% of carriers will not develop either cancer during their lifetime.

The study provides support for genetic screening for pathogenic BRCA1/2 mutations, especially in high-risk populations, according to Levy-Lahad.

“For me, the results are part of a bigger picture.... I think we should be moving towards general population screening, certainly in high-risk populations like Ashkenazi Jews,” she said.

In Israel, that decision has already been made: a new policy, introduced in January 2020, offers testing for common BRCA1/2 mutations for all Ashkenazi Jewish women.

However, women in other countries may also benefit from testing, she argues. About half of BRCA1/2 carriers in a general population like that of the United States do not have a family history that would indicate a need for testing. That means many women who carry these mutations may not be taking advantage of recommended surveillance and prevention measures, she said.

But screening for BRCA1/2 mutations becomes more complicated when applied to more general populations, she acknowledged.

About 2.5% of women of Ashkenazi Jewish descent carry pathogenic mutations for BRCA1/2, compared to 0.5% in the general White population.

Also, screening in the Ashkenazi Jewish population is probably simpler than in the general population. Just three mutations are definitely known to cause disease and need to be tested for among Ashkenazi Jews. Screening in a larger population would require full sequencing of the gene. That increases the likelihood of finding variants of unknown significance (VUSs), which muddies the water. Knowledge is incomplete about whether some of these VUSs increase cancer risk, and physicians do not always know how to manage them in women who test positive.

Moreover, Israel has a national health system. Screening in a country without universal health insurance such as the United States raises questions about whether follow-up would be covered by insurance carriers for women who test positive.

Mehmet Copur, MD, an oncologist at Morrison Cancer Center in Hastings, Nebraska, questions how general population screening could be done in “real life.”

“These findings should be taken into consideration in the context of the patient population who would agree to genetic testing, who would agree to comply with the recommended guidelines for risk reduction, and who would have insurance coverage or resources to comply with the recommendations,” Copur told Medscape Medical News.

“If BRCA-positive patients did not or could not follow these recommendations, the results would different,” he added.

The most crucial component of screening for these mutations is genetic counselors, who are in short supply in the United States, according to Copur.

Another issue is that of cost. Genetic counseling is not always covered by insurance, especially for individuals who do not have a family history of BRCA-related cancers. Genetic testing is not cheap, and the costs of monitoring women who test positive could be prohibitive, especially in a healthcare system burdened by COVID-19.

“Whether our current healthcare system could bear the cost of such a change is up for debate. The screening itself may be feasible, but offering lifelong surveillance to every woman identified with mutations could present huge capacity issues,” Copur said. “Maybe in the future, the healthcare system can be ready for such an undertaking, but I don’t think we are there yet.”

Although she acknowledges the differences in risk between Ashkenazi Jews and the general population, Levy-Lahad thinks not having screening is like “throwing the baby out with the bath water.”

“Maybe we’re not ready for total general population screening, but I think we have to start thinking along those lines,” she said. “We have this incredible tool for cancer prevention, and we should really be using it, certainly in populations like Ashkenazi Jews.”

Researchers conducted a retrospective analysis that included 105 women diagnosed with breast cancer at Shaare Zedek Medical Center in Jerusalem between 2005 and 2016. Forty-two women knew they were carriers before their breast cancer diagnosis, and 63 learned of their carrier status only after diagnosis. Of the participants, 83% were Ashkenazi Jews. For both prediagnosis and postdiagnosis groups, the age at diagnosis was the same (50.4 years). For both groups, distributions of pathogenic mutations were similar. There were no significant differences in hormone receptor or ERBB2 status.

Among women who knew they were carriers before diagnosis, 80.9% (34/42) were diagnosed either with ductal carcinoma in situ or stage 1 disease. Only 9.5% (4/42) of these women were diagnosed with disease of stage 2 or higher.

In comparison, among women who learned their carrier status after diagnosis, 30% (19/63) had early-stage disease at diagnosis, and 52.4% (33/63) were diagnosed at stage 2 or higher (P < .001).

Compared to women who knew their carrier status before diagnosis, women who found out after diagnosis had 12 times higher odds of being diagnosed with disease of advanced clinical stage (P = .001) and eight times higher odds of being diagnosed with disease of advanced pathologic stage (P = .002).

A sentinel node biopsy was sufficient in 85.7% (36/42) of women who knew their carrier status before diagnosis; 7.2% (3/42) of these women needed a full lymph node dissection. In contrast, 3.2% (2/63) of women who learned their carrier status after diagnosis underwent sentinel node biopsy, and 34.9% (25/105) needed a full lymph node dissection (P < .001).

Among women who knew their carrier status before diagnosis, 54.8% (23/42) did not need chemotherapy at all, and none needed neoadjuvant chemotherapy. Only 4.8% (3/63) of women who learned their mutation status after diagnosis were able to forgo chemotherapy (P < .001); 22.2% (14/63) needed neoadjuvant therapy (P = .001).

These findings appeared to translate into better outcomes. Overall 5-year survival was significantly higher among women who knew their carrier status before diagnosis compared to women who found out afterward (94% [SE 4%] vs 78% [SE 5%]; P = .03). Only two of 42 women (4.8%) in the prediagnosis group died, compared to 16 of 63 (25.4%) in the postdiagnosis group.

Analyses that controlled for year at diagnosis showed that women who learned their carrier status before diagnosis had significantly lower risk for overall mortality compared with those who found out after diagnosis (hazard ratio [HR], 0.20; 95% CI, 0.04 – 0.93; P = .04). However, these results lost significance when controlled for age, socioeconomic index, family history, and gene variant (HR, 0.16; 95% CI, 0.02 – 1.4; P = .10).

Higher socioeconomic status (HR, 0.76; 95% CI, 0.6 – 0.97; P = .03), gene variant (BRCA2 vs BRCA1: HR, 0.15; 95% CI, 0.03 – 0.75; P = .02), and age at diagnosis (HR, 1.047; 95% CI, 1.003 – 1.093; P = .04) were all associated with overall mortality.

“I can’t infer causation, but we suspect that the reason for these results is the difference in follow-up,” Levy-Lahad said.

Most of the women (95.2%, 40/42) who knew their carrier status before diagnosis received their follow-up at the medical center’s high-risk carrier clinic. Twenty-seven of 42 (64.3%) of these women were diagnosed with breast MRI. By contrast, only 1.6% (1/63) of women who found out their carrier status after diagnosis were diagnosed with breast MRI. Breast MRI is not routinely used for breast cancer screening but can be more sensitive than mammography for detecting breast cancer.

The study was funded by the Breast Cancer Research Foundation and by a gift from Ellie and David Werber to ShaareZedek Medical Center.

Levy-Lahad received grants from the Breast Cancer Research Foundation and from the Israel Cancer Association during the conduct of the study and personal fees from AstraZeneca outside the submitted work. Copur has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A study has shown for the first time that knowing BRCA1/2 mutation status before a breast cancer diagnosis was associated with better survival.

The study, conducted among Ashkenazi Jewish women in Israel, showed that among women who knew their carrier status before they developed breast cancer, diagnoses were made at an earlier disease stage and 5-year survival was improved compared to women who learned their carrier status only after their disease had been diagnosed.

The study was published online on July 9 in JAMA Oncology.

“I don’t want to belittle the complexities of knowing that you’re a carrier. But I think these results really show that knowledge is power,” first author Ephrat Levy-Lahad, MD, director of the medical genetics unit at Shaare Zedek Medical Center in Jerusalem, Israel, told Medscape Medical News.

Carrying a BRCA1/2 pathogenic mutation is associated with a 70% to 80% lifetime risk for breast cancer and about a 10% to 50% lifetime risk for ovarian cancer, depending on the specific mutation. Only about 10% of carriers will not develop either cancer during their lifetime.

The study provides support for genetic screening for pathogenic BRCA1/2 mutations, especially in high-risk populations, according to Levy-Lahad.

“For me, the results are part of a bigger picture.... I think we should be moving towards general population screening, certainly in high-risk populations like Ashkenazi Jews,” she said.

In Israel, that decision has already been made: a new policy, introduced in January 2020, offers testing for common BRCA1/2 mutations for all Ashkenazi Jewish women.

However, women in other countries may also benefit from testing, she argues. About half of BRCA1/2 carriers in a general population like that of the United States do not have a family history that would indicate a need for testing. That means many women who carry these mutations may not be taking advantage of recommended surveillance and prevention measures, she said.

But screening for BRCA1/2 mutations becomes more complicated when applied to more general populations, she acknowledged.

About 2.5% of women of Ashkenazi Jewish descent carry pathogenic mutations for BRCA1/2, compared to 0.5% in the general White population.

Also, screening in the Ashkenazi Jewish population is probably simpler than in the general population. Just three mutations are definitely known to cause disease and need to be tested for among Ashkenazi Jews. Screening in a larger population would require full sequencing of the gene. That increases the likelihood of finding variants of unknown significance (VUSs), which muddies the water. Knowledge is incomplete about whether some of these VUSs increase cancer risk, and physicians do not always know how to manage them in women who test positive.

Moreover, Israel has a national health system. Screening in a country without universal health insurance such as the United States raises questions about whether follow-up would be covered by insurance carriers for women who test positive.

Mehmet Copur, MD, an oncologist at Morrison Cancer Center in Hastings, Nebraska, questions how general population screening could be done in “real life.”

“These findings should be taken into consideration in the context of the patient population who would agree to genetic testing, who would agree to comply with the recommended guidelines for risk reduction, and who would have insurance coverage or resources to comply with the recommendations,” Copur told Medscape Medical News.

“If BRCA-positive patients did not or could not follow these recommendations, the results would different,” he added.

The most crucial component of screening for these mutations is genetic counselors, who are in short supply in the United States, according to Copur.

Another issue is that of cost. Genetic counseling is not always covered by insurance, especially for individuals who do not have a family history of BRCA-related cancers. Genetic testing is not cheap, and the costs of monitoring women who test positive could be prohibitive, especially in a healthcare system burdened by COVID-19.

“Whether our current healthcare system could bear the cost of such a change is up for debate. The screening itself may be feasible, but offering lifelong surveillance to every woman identified with mutations could present huge capacity issues,” Copur said. “Maybe in the future, the healthcare system can be ready for such an undertaking, but I don’t think we are there yet.”

Although she acknowledges the differences in risk between Ashkenazi Jews and the general population, Levy-Lahad thinks not having screening is like “throwing the baby out with the bath water.”

“Maybe we’re not ready for total general population screening, but I think we have to start thinking along those lines,” she said. “We have this incredible tool for cancer prevention, and we should really be using it, certainly in populations like Ashkenazi Jews.”

Researchers conducted a retrospective analysis that included 105 women diagnosed with breast cancer at Shaare Zedek Medical Center in Jerusalem between 2005 and 2016. Forty-two women knew they were carriers before their breast cancer diagnosis, and 63 learned of their carrier status only after diagnosis. Of the participants, 83% were Ashkenazi Jews. For both prediagnosis and postdiagnosis groups, the age at diagnosis was the same (50.4 years). For both groups, distributions of pathogenic mutations were similar. There were no significant differences in hormone receptor or ERBB2 status.

Among women who knew they were carriers before diagnosis, 80.9% (34/42) were diagnosed either with ductal carcinoma in situ or stage 1 disease. Only 9.5% (4/42) of these women were diagnosed with disease of stage 2 or higher.

In comparison, among women who learned their carrier status after diagnosis, 30% (19/63) had early-stage disease at diagnosis, and 52.4% (33/63) were diagnosed at stage 2 or higher (P < .001).

Compared to women who knew their carrier status before diagnosis, women who found out after diagnosis had 12 times higher odds of being diagnosed with disease of advanced clinical stage (P = .001) and eight times higher odds of being diagnosed with disease of advanced pathologic stage (P = .002).

A sentinel node biopsy was sufficient in 85.7% (36/42) of women who knew their carrier status before diagnosis; 7.2% (3/42) of these women needed a full lymph node dissection. In contrast, 3.2% (2/63) of women who learned their carrier status after diagnosis underwent sentinel node biopsy, and 34.9% (25/105) needed a full lymph node dissection (P < .001).

Among women who knew their carrier status before diagnosis, 54.8% (23/42) did not need chemotherapy at all, and none needed neoadjuvant chemotherapy. Only 4.8% (3/63) of women who learned their mutation status after diagnosis were able to forgo chemotherapy (P < .001); 22.2% (14/63) needed neoadjuvant therapy (P = .001).

These findings appeared to translate into better outcomes. Overall 5-year survival was significantly higher among women who knew their carrier status before diagnosis compared to women who found out afterward (94% [SE 4%] vs 78% [SE 5%]; P = .03). Only two of 42 women (4.8%) in the prediagnosis group died, compared to 16 of 63 (25.4%) in the postdiagnosis group.

Analyses that controlled for year at diagnosis showed that women who learned their carrier status before diagnosis had significantly lower risk for overall mortality compared with those who found out after diagnosis (hazard ratio [HR], 0.20; 95% CI, 0.04 – 0.93; P = .04). However, these results lost significance when controlled for age, socioeconomic index, family history, and gene variant (HR, 0.16; 95% CI, 0.02 – 1.4; P = .10).

Higher socioeconomic status (HR, 0.76; 95% CI, 0.6 – 0.97; P = .03), gene variant (BRCA2 vs BRCA1: HR, 0.15; 95% CI, 0.03 – 0.75; P = .02), and age at diagnosis (HR, 1.047; 95% CI, 1.003 – 1.093; P = .04) were all associated with overall mortality.

“I can’t infer causation, but we suspect that the reason for these results is the difference in follow-up,” Levy-Lahad said.

Most of the women (95.2%, 40/42) who knew their carrier status before diagnosis received their follow-up at the medical center’s high-risk carrier clinic. Twenty-seven of 42 (64.3%) of these women were diagnosed with breast MRI. By contrast, only 1.6% (1/63) of women who found out their carrier status after diagnosis were diagnosed with breast MRI. Breast MRI is not routinely used for breast cancer screening but can be more sensitive than mammography for detecting breast cancer.

The study was funded by the Breast Cancer Research Foundation and by a gift from Ellie and David Werber to ShaareZedek Medical Center.

Levy-Lahad received grants from the Breast Cancer Research Foundation and from the Israel Cancer Association during the conduct of the study and personal fees from AstraZeneca outside the submitted work. Copur has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Starting breast cancer screening in young adulthood has the potential to sharply reduce deaths from the disease among women who have received chest radiation for childhood cancer, a modeling study suggests.

Two strategies – annual mammography with MRI and annual MRI alone – at least halved breast cancer mortality when started at the ages of 25 or 30 years.

Jennifer M. Yeh, PhD, of Harvard Medical School in Boston and colleagues reported these results in the Annals of Internal Medicine.

When cost was also considered, 30 years emerged as the preferred starting age, dropping the incremental cost-effectiveness ratio (ICER) below the generally accepted threshold of $100,000 per quality-adjusted life-year gained.

“Our findings underscore the importance of making sure that young women previously treated with chest radiation are informed about their elevated breast cancer risk and the benefits of routine screening. Both primary care providers and oncologists who care for survivors should discuss breast cancer screening with these patients,” Dr. Yeh and colleagues wrote.

“Screening guidelines should emphasize the importance of MRI screening (with or without mammography) among survivors,” the authors recommended. “Our findings also highlight the importance of ensuring that survivors have access to health insurance coverage for MRI screening.”
 

Implications for awareness, coverage

“My hope is that, by showing the significantly decreased risk of death associated with early breast cancer screening, with harm-benefit ratios considerably lower than benchmarks for average-risk women, this study will help health insurance companies see the benefit in covering early screening for at-risk survivors,” commented Karen E. Effinger, MD, of Emory University, Atlanta, and the Aflac Cancer & Blood Disorders Center at Children’s Healthcare of Atlanta.

“In many survivors, the cost of current screening [as recommended by] guidelines is prohibitive,” added Dr. Effinger, who was not involved in the current study.

The main concern regarding the study’s findings is generalizability to the contemporary era, given the use of a cohort diagnosed and treated decades ago and changes in radiation techniques and dosing since then, she noted in an interview. This limitation was addressed in a sensitivity analysis that halved the women’s base-case lifetime risk of breast cancer and still netted similar results.

“However, it will take many years to determine the true risk reduction of our current treatment strategies,” Dr. Effinger acknowledged.

“It is crucial that we improve our education of both survivors and our colleagues who care for these survivors, especially in regard to risk of subsequent malignancies and the benefits of screening,” Dr. Effinger maintained. “While many people are aware of the risk of breast cancer associated with BRCA mutations, the increased risk in survivors of childhood cancer is not as recognized by nononcologists. This study reinforces that increasing this awareness can save lives.”

In educating their patients about preventive care, health care providers must strike “a fine balance between discussing the risks and benefits of screening without provoking significant anxiety,” she concluded. “It is important for survivors to establish care with a primary care provider in order to develop trust and receive the guidance they need to decrease the risk of early mortality.”
 

Study details

Dr. Yeh and colleagues developed models to compare outcomes with various screening strategies among women aged 20 years who had received chest radiotherapy for childhood cancer during 1970-1986. The women had been diagnosed with Hodgkin lymphoma (55%), Wilms tumor (12%), non-Hodgkin lymphoma (8%), and other cancers.

The investigators conducted their analysis using data from the Childhood Cancer Survivor Study and other published sources, a lifetime time horizon, and a payer perspective.

The team assessed three strategies: no screening; digital mammography with MRI screening starting at 25 years of age (the current Children’s Oncology Group recommendation), 30 years, or 35 years and continuing to 74 years of age; and MRI only starting at age 25, 30, or 35 years and continuing to age 74 years.

The main study results showed that, without screening, women who had received chest radiation for childhood cancer had a 10%-11% lifetime risk of breast cancer mortality across models.

Relative to no screening, starting at age 25 years, the largest share of deaths was averted with the strategy of annual mammography with MRI – 56.3%-71.2% – or with the strategy of annual MRI alone – 55.7%-62.0%.

These two strategies also yielded the most screening tests, as well as the most false-positive test results and benign biopsy results.

For women who started screening at age 25, there were 4,188-4,879 false-positive test results per 1,000 women for mammography plus MRI and 3,283-3,764 false-positive results per 1,000 women for MRI alone.

For women who started screening at age 25, there were 1,340-1,561 benign biopsy results per 1,000 women for mammography plus MRI and 1,248-1,430 benign results per 1,000 women for MRI alone.

After cost was factored in, beginning screening at age 30 emerged as the preferred strategy to achieve an ICER threshold of less than $100,000 per quality-adjusted life-year gained.

When started at 30 years of age, annual mammography with MRI averted 54.7%-68.8% of breast cancer deaths, with an ICER of $25,400-$113,200 per quality-adjusted life-year gained. Annual MRI alone averted 54.0%-60.0% of breast cancer deaths, with an ICER of $21,800-$50,580 per quality-adjusted life-year gained.

This research was supported by grants from the National Cancer Institute, American Cancer Society, and American Lebanese Syrian Associated Charities. The authors disclosed relationships with GE Healthcare and Biovector. Dr. Effinger disclosed no relevant conflicts of interest.

SOURCE: Yeh JM et al. Ann Intern Med. 2020 Jul 7. doi: 10.7326/M19-3481.

Starting breast cancer screening in young adulthood has the potential to sharply reduce deaths from the disease among women who have received chest radiation for childhood cancer, a modeling study suggests.

Two strategies – annual mammography with MRI and annual MRI alone – at least halved breast cancer mortality when started at the ages of 25 or 30 years.

Jennifer M. Yeh, PhD, of Harvard Medical School in Boston and colleagues reported these results in the Annals of Internal Medicine.

When cost was also considered, 30 years emerged as the preferred starting age, dropping the incremental cost-effectiveness ratio (ICER) below the generally accepted threshold of $100,000 per quality-adjusted life-year gained.

“Our findings underscore the importance of making sure that young women previously treated with chest radiation are informed about their elevated breast cancer risk and the benefits of routine screening. Both primary care providers and oncologists who care for survivors should discuss breast cancer screening with these patients,” Dr. Yeh and colleagues wrote.

“Screening guidelines should emphasize the importance of MRI screening (with or without mammography) among survivors,” the authors recommended. “Our findings also highlight the importance of ensuring that survivors have access to health insurance coverage for MRI screening.”
 

Implications for awareness, coverage

“My hope is that, by showing the significantly decreased risk of death associated with early breast cancer screening, with harm-benefit ratios considerably lower than benchmarks for average-risk women, this study will help health insurance companies see the benefit in covering early screening for at-risk survivors,” commented Karen E. Effinger, MD, of Emory University, Atlanta, and the Aflac Cancer & Blood Disorders Center at Children’s Healthcare of Atlanta.

“In many survivors, the cost of current screening [as recommended by] guidelines is prohibitive,” added Dr. Effinger, who was not involved in the current study.

The main concern regarding the study’s findings is generalizability to the contemporary era, given the use of a cohort diagnosed and treated decades ago and changes in radiation techniques and dosing since then, she noted in an interview. This limitation was addressed in a sensitivity analysis that halved the women’s base-case lifetime risk of breast cancer and still netted similar results.

“However, it will take many years to determine the true risk reduction of our current treatment strategies,” Dr. Effinger acknowledged.

“It is crucial that we improve our education of both survivors and our colleagues who care for these survivors, especially in regard to risk of subsequent malignancies and the benefits of screening,” Dr. Effinger maintained. “While many people are aware of the risk of breast cancer associated with BRCA mutations, the increased risk in survivors of childhood cancer is not as recognized by nononcologists. This study reinforces that increasing this awareness can save lives.”

In educating their patients about preventive care, health care providers must strike “a fine balance between discussing the risks and benefits of screening without provoking significant anxiety,” she concluded. “It is important for survivors to establish care with a primary care provider in order to develop trust and receive the guidance they need to decrease the risk of early mortality.”
 

Study details

Dr. Yeh and colleagues developed models to compare outcomes with various screening strategies among women aged 20 years who had received chest radiotherapy for childhood cancer during 1970-1986. The women had been diagnosed with Hodgkin lymphoma (55%), Wilms tumor (12%), non-Hodgkin lymphoma (8%), and other cancers.

The investigators conducted their analysis using data from the Childhood Cancer Survivor Study and other published sources, a lifetime time horizon, and a payer perspective.

The team assessed three strategies: no screening; digital mammography with MRI screening starting at 25 years of age (the current Children’s Oncology Group recommendation), 30 years, or 35 years and continuing to 74 years of age; and MRI only starting at age 25, 30, or 35 years and continuing to age 74 years.

The main study results showed that, without screening, women who had received chest radiation for childhood cancer had a 10%-11% lifetime risk of breast cancer mortality across models.

Relative to no screening, starting at age 25 years, the largest share of deaths was averted with the strategy of annual mammography with MRI – 56.3%-71.2% – or with the strategy of annual MRI alone – 55.7%-62.0%.

These two strategies also yielded the most screening tests, as well as the most false-positive test results and benign biopsy results.

For women who started screening at age 25, there were 4,188-4,879 false-positive test results per 1,000 women for mammography plus MRI and 3,283-3,764 false-positive results per 1,000 women for MRI alone.

For women who started screening at age 25, there were 1,340-1,561 benign biopsy results per 1,000 women for mammography plus MRI and 1,248-1,430 benign results per 1,000 women for MRI alone.

After cost was factored in, beginning screening at age 30 emerged as the preferred strategy to achieve an ICER threshold of less than $100,000 per quality-adjusted life-year gained.

When started at 30 years of age, annual mammography with MRI averted 54.7%-68.8% of breast cancer deaths, with an ICER of $25,400-$113,200 per quality-adjusted life-year gained. Annual MRI alone averted 54.0%-60.0% of breast cancer deaths, with an ICER of $21,800-$50,580 per quality-adjusted life-year gained.

This research was supported by grants from the National Cancer Institute, American Cancer Society, and American Lebanese Syrian Associated Charities. The authors disclosed relationships with GE Healthcare and Biovector. Dr. Effinger disclosed no relevant conflicts of interest.

SOURCE: Yeh JM et al. Ann Intern Med. 2020 Jul 7. doi: 10.7326/M19-3481.

Starting breast cancer screening in young adulthood has the potential to sharply reduce deaths from the disease among women who have received chest radiation for childhood cancer, a modeling study suggests.

Two strategies – annual mammography with MRI and annual MRI alone – at least halved breast cancer mortality when started at the ages of 25 or 30 years.

Jennifer M. Yeh, PhD, of Harvard Medical School in Boston and colleagues reported these results in the Annals of Internal Medicine.

When cost was also considered, 30 years emerged as the preferred starting age, dropping the incremental cost-effectiveness ratio (ICER) below the generally accepted threshold of $100,000 per quality-adjusted life-year gained.

“Our findings underscore the importance of making sure that young women previously treated with chest radiation are informed about their elevated breast cancer risk and the benefits of routine screening. Both primary care providers and oncologists who care for survivors should discuss breast cancer screening with these patients,” Dr. Yeh and colleagues wrote.

“Screening guidelines should emphasize the importance of MRI screening (with or without mammography) among survivors,” the authors recommended. “Our findings also highlight the importance of ensuring that survivors have access to health insurance coverage for MRI screening.”
 

Implications for awareness, coverage

“My hope is that, by showing the significantly decreased risk of death associated with early breast cancer screening, with harm-benefit ratios considerably lower than benchmarks for average-risk women, this study will help health insurance companies see the benefit in covering early screening for at-risk survivors,” commented Karen E. Effinger, MD, of Emory University, Atlanta, and the Aflac Cancer & Blood Disorders Center at Children’s Healthcare of Atlanta.

“In many survivors, the cost of current screening [as recommended by] guidelines is prohibitive,” added Dr. Effinger, who was not involved in the current study.

The main concern regarding the study’s findings is generalizability to the contemporary era, given the use of a cohort diagnosed and treated decades ago and changes in radiation techniques and dosing since then, she noted in an interview. This limitation was addressed in a sensitivity analysis that halved the women’s base-case lifetime risk of breast cancer and still netted similar results.

“However, it will take many years to determine the true risk reduction of our current treatment strategies,” Dr. Effinger acknowledged.

“It is crucial that we improve our education of both survivors and our colleagues who care for these survivors, especially in regard to risk of subsequent malignancies and the benefits of screening,” Dr. Effinger maintained. “While many people are aware of the risk of breast cancer associated with BRCA mutations, the increased risk in survivors of childhood cancer is not as recognized by nononcologists. This study reinforces that increasing this awareness can save lives.”

In educating their patients about preventive care, health care providers must strike “a fine balance between discussing the risks and benefits of screening without provoking significant anxiety,” she concluded. “It is important for survivors to establish care with a primary care provider in order to develop trust and receive the guidance they need to decrease the risk of early mortality.”
 

Study details

Dr. Yeh and colleagues developed models to compare outcomes with various screening strategies among women aged 20 years who had received chest radiotherapy for childhood cancer during 1970-1986. The women had been diagnosed with Hodgkin lymphoma (55%), Wilms tumor (12%), non-Hodgkin lymphoma (8%), and other cancers.

The investigators conducted their analysis using data from the Childhood Cancer Survivor Study and other published sources, a lifetime time horizon, and a payer perspective.

The team assessed three strategies: no screening; digital mammography with MRI screening starting at 25 years of age (the current Children’s Oncology Group recommendation), 30 years, or 35 years and continuing to 74 years of age; and MRI only starting at age 25, 30, or 35 years and continuing to age 74 years.

The main study results showed that, without screening, women who had received chest radiation for childhood cancer had a 10%-11% lifetime risk of breast cancer mortality across models.

Relative to no screening, starting at age 25 years, the largest share of deaths was averted with the strategy of annual mammography with MRI – 56.3%-71.2% – or with the strategy of annual MRI alone – 55.7%-62.0%.

These two strategies also yielded the most screening tests, as well as the most false-positive test results and benign biopsy results.

For women who started screening at age 25, there were 4,188-4,879 false-positive test results per 1,000 women for mammography plus MRI and 3,283-3,764 false-positive results per 1,000 women for MRI alone.

For women who started screening at age 25, there were 1,340-1,561 benign biopsy results per 1,000 women for mammography plus MRI and 1,248-1,430 benign results per 1,000 women for MRI alone.

After cost was factored in, beginning screening at age 30 emerged as the preferred strategy to achieve an ICER threshold of less than $100,000 per quality-adjusted life-year gained.

When started at 30 years of age, annual mammography with MRI averted 54.7%-68.8% of breast cancer deaths, with an ICER of $25,400-$113,200 per quality-adjusted life-year gained. Annual MRI alone averted 54.0%-60.0% of breast cancer deaths, with an ICER of $21,800-$50,580 per quality-adjusted life-year gained.

This research was supported by grants from the National Cancer Institute, American Cancer Society, and American Lebanese Syrian Associated Charities. The authors disclosed relationships with GE Healthcare and Biovector. Dr. Effinger disclosed no relevant conflicts of interest.

SOURCE: Yeh JM et al. Ann Intern Med. 2020 Jul 7. doi: 10.7326/M19-3481.

Patients with early onset cancers have an increased prevalence of germline pathogenic variants, suggesting that genetic testing would be worthwhile in this population, according to a presentation at the AACR virtual meeting II.

Investigators analyzed blood samples from 1,201 patients who were aged 18-39 years when diagnosed with a solid tumor malignancy.

In this group, there were 877 patients with early onset cancers, defined as cancers for which 39 years of age is greater than 1 standard deviation below the mean age of diagnosis for the cancer type.

The remaining 324 patients had young adult cancers, defined as cancers for which 39 years of age is less than 1 standard deviation below the mean age of diagnosis.

The most common early onset cancers were breast, colorectal, kidney, pancreas, and ovarian cancer.

The most common young adult cancers were sarcoma, brain cancer, and testicular cancer, as expected, said investigator Zsofia K. Stadler, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Stadler and colleagues performed next-generation sequencing of the patient samples using a panel of up to 88 genes previously implicated in cancer predisposition. This revealed a significantly higher prevalence of germline mutations in patients with early onset cancers than in those with young adult cancers – 21% and 13%, respectively (P = .002).

In patients with only high- and moderate-risk cancer susceptibility genes, the prevalence was 15% in the early onset group and 10% in the young adult group (P = .01). “Among the early onset cancer group, pancreas, breast, and kidney cancer patients harbored the highest rates of germline mutations,” Dr. Stadler said, noting that the spectrum of mutated genes differed in early onset and young adult cancer patients.

“In early onset patients, the most commonly mutated genes were BRCA1 and BRCA2 [4.9%], Lynch syndrome genes [2.2%], ATM [1.6%], and CHECK2 [1.7%],” Dr. Stadler said. “On the other hand, in young adults, TP53 mutations [2.2%], and SDHA and SDHB mutations dominated [1.9%], with the majority of mutations occurring in sarcoma patients.”

These findings suggest the prevalence of inherited cancer susceptibility syndromes in young adults with cancer is not uniform.

“We found a very high prevalence of germline mutations in young patients with cancer types that typically present at later ages,” Dr. Stadler said, referring to the early onset patients.

Conversely, the young adult cancer patients had a prevalence and spectrum of mutations more similar to what is seen in pediatric cancer populations, she noted.

The findings are surprising, according to AACR past president Elaine R. Mardis, PhD, of The Ohio State University in Columbus.

Dr. Mardis said the results show that, in young adults with early onset cancers, “the germline prevalence of these mutations is significantly higher than we had previously thought.”

“Although representing only about 4% of all cancers, young adults with cancer ... face unique challenges,” Dr. Stadler said. “Identifying whether a young patient’s cancer occurred in the setting of an inherited cancer predisposition syndrome is especially important in this patient population.”

Such knowledge “can significantly impact the risk of second primary cancers and the need for increased surveillance measures or even risk-reducing surgeries,” Dr. Stadler explained. She added that it can also have implications for identifying at-risk family members, such as younger siblings or children who should pursue genetic testing and appropriate prevention measures.

“Our results suggest that, among patients with early onset cancer, the increased prevalence of germline mutations supports a role for genetic testing, irrespective of tumor type,” Dr. Stadler said.

This study was partially funded by the Precision, Interception and Prevention Program, the Robert and Katie Niehaus Center for Inherited Cancer Genomics, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, and a National Cancer Institute Cancer Center Core Grant. Dr. Stadler reported that an immediate family member serves as a consultant in ophthalmology for Allergan, Adverum Biotechnologies, Alimera Sciences, BioMarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Mardis disclosed relationships with Qiagen NV, Pact Pharma LLC, Moderna Inc., and Interpreta LLC.

sworcester@mdedge.com

SOURCE: Stadler Z et al. AACR 2020, Abstract 1122.

Patients with early onset cancers have an increased prevalence of germline pathogenic variants, suggesting that genetic testing would be worthwhile in this population, according to a presentation at the AACR virtual meeting II.

Investigators analyzed blood samples from 1,201 patients who were aged 18-39 years when diagnosed with a solid tumor malignancy.

In this group, there were 877 patients with early onset cancers, defined as cancers for which 39 years of age is greater than 1 standard deviation below the mean age of diagnosis for the cancer type.

The remaining 324 patients had young adult cancers, defined as cancers for which 39 years of age is less than 1 standard deviation below the mean age of diagnosis.

The most common early onset cancers were breast, colorectal, kidney, pancreas, and ovarian cancer.

The most common young adult cancers were sarcoma, brain cancer, and testicular cancer, as expected, said investigator Zsofia K. Stadler, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Stadler and colleagues performed next-generation sequencing of the patient samples using a panel of up to 88 genes previously implicated in cancer predisposition. This revealed a significantly higher prevalence of germline mutations in patients with early onset cancers than in those with young adult cancers – 21% and 13%, respectively (P = .002).

In patients with only high- and moderate-risk cancer susceptibility genes, the prevalence was 15% in the early onset group and 10% in the young adult group (P = .01). “Among the early onset cancer group, pancreas, breast, and kidney cancer patients harbored the highest rates of germline mutations,” Dr. Stadler said, noting that the spectrum of mutated genes differed in early onset and young adult cancer patients.

“In early onset patients, the most commonly mutated genes were BRCA1 and BRCA2 [4.9%], Lynch syndrome genes [2.2%], ATM [1.6%], and CHECK2 [1.7%],” Dr. Stadler said. “On the other hand, in young adults, TP53 mutations [2.2%], and SDHA and SDHB mutations dominated [1.9%], with the majority of mutations occurring in sarcoma patients.”

These findings suggest the prevalence of inherited cancer susceptibility syndromes in young adults with cancer is not uniform.

“We found a very high prevalence of germline mutations in young patients with cancer types that typically present at later ages,” Dr. Stadler said, referring to the early onset patients.

Conversely, the young adult cancer patients had a prevalence and spectrum of mutations more similar to what is seen in pediatric cancer populations, she noted.

The findings are surprising, according to AACR past president Elaine R. Mardis, PhD, of The Ohio State University in Columbus.

Dr. Mardis said the results show that, in young adults with early onset cancers, “the germline prevalence of these mutations is significantly higher than we had previously thought.”

“Although representing only about 4% of all cancers, young adults with cancer ... face unique challenges,” Dr. Stadler said. “Identifying whether a young patient’s cancer occurred in the setting of an inherited cancer predisposition syndrome is especially important in this patient population.”

Such knowledge “can significantly impact the risk of second primary cancers and the need for increased surveillance measures or even risk-reducing surgeries,” Dr. Stadler explained. She added that it can also have implications for identifying at-risk family members, such as younger siblings or children who should pursue genetic testing and appropriate prevention measures.

“Our results suggest that, among patients with early onset cancer, the increased prevalence of germline mutations supports a role for genetic testing, irrespective of tumor type,” Dr. Stadler said.

This study was partially funded by the Precision, Interception and Prevention Program, the Robert and Katie Niehaus Center for Inherited Cancer Genomics, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, and a National Cancer Institute Cancer Center Core Grant. Dr. Stadler reported that an immediate family member serves as a consultant in ophthalmology for Allergan, Adverum Biotechnologies, Alimera Sciences, BioMarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Mardis disclosed relationships with Qiagen NV, Pact Pharma LLC, Moderna Inc., and Interpreta LLC.

sworcester@mdedge.com

SOURCE: Stadler Z et al. AACR 2020, Abstract 1122.

Patients with early onset cancers have an increased prevalence of germline pathogenic variants, suggesting that genetic testing would be worthwhile in this population, according to a presentation at the AACR virtual meeting II.

Investigators analyzed blood samples from 1,201 patients who were aged 18-39 years when diagnosed with a solid tumor malignancy.

In this group, there were 877 patients with early onset cancers, defined as cancers for which 39 years of age is greater than 1 standard deviation below the mean age of diagnosis for the cancer type.

The remaining 324 patients had young adult cancers, defined as cancers for which 39 years of age is less than 1 standard deviation below the mean age of diagnosis.

The most common early onset cancers were breast, colorectal, kidney, pancreas, and ovarian cancer.

The most common young adult cancers were sarcoma, brain cancer, and testicular cancer, as expected, said investigator Zsofia K. Stadler, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Stadler and colleagues performed next-generation sequencing of the patient samples using a panel of up to 88 genes previously implicated in cancer predisposition. This revealed a significantly higher prevalence of germline mutations in patients with early onset cancers than in those with young adult cancers – 21% and 13%, respectively (P = .002).

In patients with only high- and moderate-risk cancer susceptibility genes, the prevalence was 15% in the early onset group and 10% in the young adult group (P = .01). “Among the early onset cancer group, pancreas, breast, and kidney cancer patients harbored the highest rates of germline mutations,” Dr. Stadler said, noting that the spectrum of mutated genes differed in early onset and young adult cancer patients.

“In early onset patients, the most commonly mutated genes were BRCA1 and BRCA2 [4.9%], Lynch syndrome genes [2.2%], ATM [1.6%], and CHECK2 [1.7%],” Dr. Stadler said. “On the other hand, in young adults, TP53 mutations [2.2%], and SDHA and SDHB mutations dominated [1.9%], with the majority of mutations occurring in sarcoma patients.”

These findings suggest the prevalence of inherited cancer susceptibility syndromes in young adults with cancer is not uniform.

“We found a very high prevalence of germline mutations in young patients with cancer types that typically present at later ages,” Dr. Stadler said, referring to the early onset patients.

Conversely, the young adult cancer patients had a prevalence and spectrum of mutations more similar to what is seen in pediatric cancer populations, she noted.

The findings are surprising, according to AACR past president Elaine R. Mardis, PhD, of The Ohio State University in Columbus.

Dr. Mardis said the results show that, in young adults with early onset cancers, “the germline prevalence of these mutations is significantly higher than we had previously thought.”

“Although representing only about 4% of all cancers, young adults with cancer ... face unique challenges,” Dr. Stadler said. “Identifying whether a young patient’s cancer occurred in the setting of an inherited cancer predisposition syndrome is especially important in this patient population.”

Such knowledge “can significantly impact the risk of second primary cancers and the need for increased surveillance measures or even risk-reducing surgeries,” Dr. Stadler explained. She added that it can also have implications for identifying at-risk family members, such as younger siblings or children who should pursue genetic testing and appropriate prevention measures.

“Our results suggest that, among patients with early onset cancer, the increased prevalence of germline mutations supports a role for genetic testing, irrespective of tumor type,” Dr. Stadler said.

This study was partially funded by the Precision, Interception and Prevention Program, the Robert and Katie Niehaus Center for Inherited Cancer Genomics, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, and a National Cancer Institute Cancer Center Core Grant. Dr. Stadler reported that an immediate family member serves as a consultant in ophthalmology for Allergan, Adverum Biotechnologies, Alimera Sciences, BioMarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Mardis disclosed relationships with Qiagen NV, Pact Pharma LLC, Moderna Inc., and Interpreta LLC.

sworcester@mdedge.com

SOURCE: Stadler Z et al. AACR 2020, Abstract 1122.

Obesity has been shown to have an impact on the risk of developing breast cancer and on prognosis. A new study suggests that it may also have an effect on treatment.

A high body mass index (BMI) at the time of breast cancer diagnosis could reduce the efficacy of taxane-based adjuvant chemotherapy, worsening survival outcomes, the study suggests.

That study investigated docetaxel (Taxotere), which is a “lipophilic drug, suggesting that fat present in the body could absorb part of the drug before it can reach the tumor,” commented lead author Christine Desmedt, PhD, of the Laboratory for Translational Breast Cancer Research, Department of Oncology, Leuven, Belgium.

“These results also make us wonder whether other chemotherapy drugs from the same family, like paclitaxel (Taxol), will show the same effect,” she said in a statement.

If follow-up research confirms that the findings are related solely to the pharmacologic characteristics of docetaxel, the results may also apply to its use in other types of cancer, including prostate cancer and lung cancer, she added.

The finding that taxane chemotherapy was less effective in overweight patients “is a provocative observation,” commented Harold Burstein, MD, PhD, an oncologist and clinical investigator at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, Massachusetts.

“It should be explored in other trials that looked at adding taxanes to standard chemotherapy,” he told Medscape Medical News.
 

Worse outcomes in patients with high BMI

The study, published online in the Journal of Clinical Oncology, was a retrospective reanalysis of data from the phase 3 BIG 2-98 trial.

It shows that overweight and obese patients treated with a chemotherapy regimen based on docetaxel had significantly worse disease-free survival (DFS) and overall survival (OS) compared with lean patients treated with the same chemotherapy regimen.

Conversely, for patients treated with an adjuvant chemotherapy regimen that did not include docetaxel, there was no difference in DFS, OS, or in the rates of distant metastases in regard to BMI.

The finding “highlights a differential response to docetaxel according to BMI, which calls for a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer,” say the researchers. “These results now must be confirmed in additional series.”

The findings call into question results from earlier randomized clinical trials that did not evaluate the efficacy of most cancer drugs on the basis of patient adiposity, the researchers say.

Desmedt emphasized that more research is needed “before changes in treatment can be implemented.”

Experts approached by Medscape Medical News for comment agreed.

“It is important to remember that breast cancer patients needing chemotherapy should still receive the usual chemotherapy regimens, including taxanes, regardless of their weight or habitus,” commented Burstein, who is also professor of medicine at Harvard University.

These data highlight a persistent disparity in breast cancer outcomes, he told Medscape Medical News. Previous studies have shown that overweight patients often have less favorable outcomes. “There are many contributors to poor health outcomes in people with higher BMI, including concurrent health issues such as diabetes and/or hypertension, and unfortunately, the clear link between socioeconomic status and obesity,” he added.

Megan Kruse, MD, of the department of hematology and medical oncology at the Cleveland Clinic, said she “would not make changes in my treatment recommendations based on this study alone.”

Kruse was surprised that when the analysis was restricted to patients who received a relative dose intensity ≥85% for docetaxel, the same reduced rates of DFS and OS were seen as in patients with a high BMI.

“One may have suspected, based on the overall results, that patients with inferior survival outcomes actually received less chemotherapy due to [the] tendency to cap doses of chemotherapy in patients with high BMIs,” she explained.

“Since this analysis keeps dose intensity in mind, the association between BMI and survival outcomes is stronger in my mind. It does not, however, rule out that there are other confounding factors,” Kruse told Medscape Medical News.

Whether the results can be replicated in other retrospective clinical trials remains to be seen, she commented. Noting that the investigators plan to develop a prospective pharmacokinetics study across the BMI spectrum, Kruse added: “This will be of great interest as we plan curative-intent chemotherapy trials moving forward.”

Study details

For the current study, the investigators analyzed data from all 2,887 breast cancer patients enrolled in the adjuvant BIG 2-98 trial. They compared the survival outcomes of those who received docetaxel-based chemotherapy with those who received non-docetaxel-based chemotherapy in relation to their BMI. Patients with a BMI of 18.5 to 25 kg/m were classified as lean; patients with a BMI of 25-30 were classified as overweight; and those with a BMI ≥30 were classified as obese.

The researchers also assessed a second-order interaction on the basis of treatment, BMI, and estrogen receptor (ER) status.

The results showed that in the overweight women, compared with lean women, the adjusted hazard ratios (HRs) for DFS and OS were 1.12 (95% CI, 98 – 1.50; P = .21) and 1.27 (95% CI,101 – 1.60; P = .04), respectively. For obese vs lean patients, the HRs for DFS and OS were 1.32 (95% CI, 108 – 162; P = .007) and 1.63 (95% CI, 1.27 – 2.09; P < .001), respectively.

The survival outcomes were similar when only those patients who received a relative dose intensity ≥85% for docetaxel were considered. However, when ER-negative and ER-positive tumors were considered separately, the researchers found evidence of a joint modifying role of BMI and ER status on treatment effect for DFS (adjusted P =.06) and OS (adjusted P = .04).

“[I]t appears that the benefit for docetaxel-based versus nondocetaxel-based treatment could be limited to lean and overweight patients with ER-positive tumors and, possibly, to lean patients with ER-negative tumors…,” Desmedt and colleagues comment.

It may even be possible that docetaxel-based treatment could be detrimental for overweight patients with ER-negative tumors, they note, but warn that these results should be interpreted with caution.

The investigators note that, worldwide, the proportion of women with increased adiposity has been increasing for decades. In Europe, it is estimated that more than 50% of women are overweight and obese. In the United States, almost 64% of women have a BMI >25 kg/mg².

Previous studies have shown that, in postmenopausal women, a high BMI is associated with a higher risk of developing breast cancer and that, in women who do develop breast cancer, the prognosis is worse. In addition, a recent study demonstrated that increased adiposity can raise the risk for breast cancer in postmenopausal women whose BMI is in the normal range.

The study was funded in part by Fondation Cancer Luxemburg and Associazione Italiana per la Ricerca sul Cancro AIRC. Desmedt has disclosed no relevant financial relationships. A number of study coauthors reported relationships with industry.

This story first appeared on Medscape.com.

Obesity has been shown to have an impact on the risk of developing breast cancer and on prognosis. A new study suggests that it may also have an effect on treatment.

A high body mass index (BMI) at the time of breast cancer diagnosis could reduce the efficacy of taxane-based adjuvant chemotherapy, worsening survival outcomes, the study suggests.

That study investigated docetaxel (Taxotere), which is a “lipophilic drug, suggesting that fat present in the body could absorb part of the drug before it can reach the tumor,” commented lead author Christine Desmedt, PhD, of the Laboratory for Translational Breast Cancer Research, Department of Oncology, Leuven, Belgium.

“These results also make us wonder whether other chemotherapy drugs from the same family, like paclitaxel (Taxol), will show the same effect,” she said in a statement.

If follow-up research confirms that the findings are related solely to the pharmacologic characteristics of docetaxel, the results may also apply to its use in other types of cancer, including prostate cancer and lung cancer, she added.

The finding that taxane chemotherapy was less effective in overweight patients “is a provocative observation,” commented Harold Burstein, MD, PhD, an oncologist and clinical investigator at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, Massachusetts.

“It should be explored in other trials that looked at adding taxanes to standard chemotherapy,” he told Medscape Medical News.
 

Worse outcomes in patients with high BMI

The study, published online in the Journal of Clinical Oncology, was a retrospective reanalysis of data from the phase 3 BIG 2-98 trial.

It shows that overweight and obese patients treated with a chemotherapy regimen based on docetaxel had significantly worse disease-free survival (DFS) and overall survival (OS) compared with lean patients treated with the same chemotherapy regimen.

Conversely, for patients treated with an adjuvant chemotherapy regimen that did not include docetaxel, there was no difference in DFS, OS, or in the rates of distant metastases in regard to BMI.

The finding “highlights a differential response to docetaxel according to BMI, which calls for a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer,” say the researchers. “These results now must be confirmed in additional series.”

The findings call into question results from earlier randomized clinical trials that did not evaluate the efficacy of most cancer drugs on the basis of patient adiposity, the researchers say.

Desmedt emphasized that more research is needed “before changes in treatment can be implemented.”

Experts approached by Medscape Medical News for comment agreed.

“It is important to remember that breast cancer patients needing chemotherapy should still receive the usual chemotherapy regimens, including taxanes, regardless of their weight or habitus,” commented Burstein, who is also professor of medicine at Harvard University.

These data highlight a persistent disparity in breast cancer outcomes, he told Medscape Medical News. Previous studies have shown that overweight patients often have less favorable outcomes. “There are many contributors to poor health outcomes in people with higher BMI, including concurrent health issues such as diabetes and/or hypertension, and unfortunately, the clear link between socioeconomic status and obesity,” he added.

Megan Kruse, MD, of the department of hematology and medical oncology at the Cleveland Clinic, said she “would not make changes in my treatment recommendations based on this study alone.”

Kruse was surprised that when the analysis was restricted to patients who received a relative dose intensity ≥85% for docetaxel, the same reduced rates of DFS and OS were seen as in patients with a high BMI.

“One may have suspected, based on the overall results, that patients with inferior survival outcomes actually received less chemotherapy due to [the] tendency to cap doses of chemotherapy in patients with high BMIs,” she explained.

“Since this analysis keeps dose intensity in mind, the association between BMI and survival outcomes is stronger in my mind. It does not, however, rule out that there are other confounding factors,” Kruse told Medscape Medical News.

Whether the results can be replicated in other retrospective clinical trials remains to be seen, she commented. Noting that the investigators plan to develop a prospective pharmacokinetics study across the BMI spectrum, Kruse added: “This will be of great interest as we plan curative-intent chemotherapy trials moving forward.”

Study details

For the current study, the investigators analyzed data from all 2,887 breast cancer patients enrolled in the adjuvant BIG 2-98 trial. They compared the survival outcomes of those who received docetaxel-based chemotherapy with those who received non-docetaxel-based chemotherapy in relation to their BMI. Patients with a BMI of 18.5 to 25 kg/m were classified as lean; patients with a BMI of 25-30 were classified as overweight; and those with a BMI ≥30 were classified as obese.

The researchers also assessed a second-order interaction on the basis of treatment, BMI, and estrogen receptor (ER) status.

The results showed that in the overweight women, compared with lean women, the adjusted hazard ratios (HRs) for DFS and OS were 1.12 (95% CI, 98 – 1.50; P = .21) and 1.27 (95% CI,101 – 1.60; P = .04), respectively. For obese vs lean patients, the HRs for DFS and OS were 1.32 (95% CI, 108 – 162; P = .007) and 1.63 (95% CI, 1.27 – 2.09; P < .001), respectively.

The survival outcomes were similar when only those patients who received a relative dose intensity ≥85% for docetaxel were considered. However, when ER-negative and ER-positive tumors were considered separately, the researchers found evidence of a joint modifying role of BMI and ER status on treatment effect for DFS (adjusted P =.06) and OS (adjusted P = .04).

“[I]t appears that the benefit for docetaxel-based versus nondocetaxel-based treatment could be limited to lean and overweight patients with ER-positive tumors and, possibly, to lean patients with ER-negative tumors…,” Desmedt and colleagues comment.

It may even be possible that docetaxel-based treatment could be detrimental for overweight patients with ER-negative tumors, they note, but warn that these results should be interpreted with caution.

The investigators note that, worldwide, the proportion of women with increased adiposity has been increasing for decades. In Europe, it is estimated that more than 50% of women are overweight and obese. In the United States, almost 64% of women have a BMI >25 kg/mg².

Previous studies have shown that, in postmenopausal women, a high BMI is associated with a higher risk of developing breast cancer and that, in women who do develop breast cancer, the prognosis is worse. In addition, a recent study demonstrated that increased adiposity can raise the risk for breast cancer in postmenopausal women whose BMI is in the normal range.

The study was funded in part by Fondation Cancer Luxemburg and Associazione Italiana per la Ricerca sul Cancro AIRC. Desmedt has disclosed no relevant financial relationships. A number of study coauthors reported relationships with industry.

This story first appeared on Medscape.com.

Obesity has been shown to have an impact on the risk of developing breast cancer and on prognosis. A new study suggests that it may also have an effect on treatment.

A high body mass index (BMI) at the time of breast cancer diagnosis could reduce the efficacy of taxane-based adjuvant chemotherapy, worsening survival outcomes, the study suggests.

That study investigated docetaxel (Taxotere), which is a “lipophilic drug, suggesting that fat present in the body could absorb part of the drug before it can reach the tumor,” commented lead author Christine Desmedt, PhD, of the Laboratory for Translational Breast Cancer Research, Department of Oncology, Leuven, Belgium.

“These results also make us wonder whether other chemotherapy drugs from the same family, like paclitaxel (Taxol), will show the same effect,” she said in a statement.

If follow-up research confirms that the findings are related solely to the pharmacologic characteristics of docetaxel, the results may also apply to its use in other types of cancer, including prostate cancer and lung cancer, she added.

The finding that taxane chemotherapy was less effective in overweight patients “is a provocative observation,” commented Harold Burstein, MD, PhD, an oncologist and clinical investigator at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, Massachusetts.

“It should be explored in other trials that looked at adding taxanes to standard chemotherapy,” he told Medscape Medical News.
 

Worse outcomes in patients with high BMI

The study, published online in the Journal of Clinical Oncology, was a retrospective reanalysis of data from the phase 3 BIG 2-98 trial.

It shows that overweight and obese patients treated with a chemotherapy regimen based on docetaxel had significantly worse disease-free survival (DFS) and overall survival (OS) compared with lean patients treated with the same chemotherapy regimen.

Conversely, for patients treated with an adjuvant chemotherapy regimen that did not include docetaxel, there was no difference in DFS, OS, or in the rates of distant metastases in regard to BMI.

The finding “highlights a differential response to docetaxel according to BMI, which calls for a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer,” say the researchers. “These results now must be confirmed in additional series.”

The findings call into question results from earlier randomized clinical trials that did not evaluate the efficacy of most cancer drugs on the basis of patient adiposity, the researchers say.

Desmedt emphasized that more research is needed “before changes in treatment can be implemented.”

Experts approached by Medscape Medical News for comment agreed.

“It is important to remember that breast cancer patients needing chemotherapy should still receive the usual chemotherapy regimens, including taxanes, regardless of their weight or habitus,” commented Burstein, who is also professor of medicine at Harvard University.

These data highlight a persistent disparity in breast cancer outcomes, he told Medscape Medical News. Previous studies have shown that overweight patients often have less favorable outcomes. “There are many contributors to poor health outcomes in people with higher BMI, including concurrent health issues such as diabetes and/or hypertension, and unfortunately, the clear link between socioeconomic status and obesity,” he added.

Megan Kruse, MD, of the department of hematology and medical oncology at the Cleveland Clinic, said she “would not make changes in my treatment recommendations based on this study alone.”

Kruse was surprised that when the analysis was restricted to patients who received a relative dose intensity ≥85% for docetaxel, the same reduced rates of DFS and OS were seen as in patients with a high BMI.

“One may have suspected, based on the overall results, that patients with inferior survival outcomes actually received less chemotherapy due to [the] tendency to cap doses of chemotherapy in patients with high BMIs,” she explained.

“Since this analysis keeps dose intensity in mind, the association between BMI and survival outcomes is stronger in my mind. It does not, however, rule out that there are other confounding factors,” Kruse told Medscape Medical News.

Whether the results can be replicated in other retrospective clinical trials remains to be seen, she commented. Noting that the investigators plan to develop a prospective pharmacokinetics study across the BMI spectrum, Kruse added: “This will be of great interest as we plan curative-intent chemotherapy trials moving forward.”

Study details

For the current study, the investigators analyzed data from all 2,887 breast cancer patients enrolled in the adjuvant BIG 2-98 trial. They compared the survival outcomes of those who received docetaxel-based chemotherapy with those who received non-docetaxel-based chemotherapy in relation to their BMI. Patients with a BMI of 18.5 to 25 kg/m were classified as lean; patients with a BMI of 25-30 were classified as overweight; and those with a BMI ≥30 were classified as obese.

The researchers also assessed a second-order interaction on the basis of treatment, BMI, and estrogen receptor (ER) status.

The results showed that in the overweight women, compared with lean women, the adjusted hazard ratios (HRs) for DFS and OS were 1.12 (95% CI, 98 – 1.50; P = .21) and 1.27 (95% CI,101 – 1.60; P = .04), respectively. For obese vs lean patients, the HRs for DFS and OS were 1.32 (95% CI, 108 – 162; P = .007) and 1.63 (95% CI, 1.27 – 2.09; P < .001), respectively.

The survival outcomes were similar when only those patients who received a relative dose intensity ≥85% for docetaxel were considered. However, when ER-negative and ER-positive tumors were considered separately, the researchers found evidence of a joint modifying role of BMI and ER status on treatment effect for DFS (adjusted P =.06) and OS (adjusted P = .04).

“[I]t appears that the benefit for docetaxel-based versus nondocetaxel-based treatment could be limited to lean and overweight patients with ER-positive tumors and, possibly, to lean patients with ER-negative tumors…,” Desmedt and colleagues comment.

It may even be possible that docetaxel-based treatment could be detrimental for overweight patients with ER-negative tumors, they note, but warn that these results should be interpreted with caution.

The investigators note that, worldwide, the proportion of women with increased adiposity has been increasing for decades. In Europe, it is estimated that more than 50% of women are overweight and obese. In the United States, almost 64% of women have a BMI >25 kg/mg².

Previous studies have shown that, in postmenopausal women, a high BMI is associated with a higher risk of developing breast cancer and that, in women who do develop breast cancer, the prognosis is worse. In addition, a recent study demonstrated that increased adiposity can raise the risk for breast cancer in postmenopausal women whose BMI is in the normal range.

The study was funded in part by Fondation Cancer Luxemburg and Associazione Italiana per la Ricerca sul Cancro AIRC. Desmedt has disclosed no relevant financial relationships. A number of study coauthors reported relationships with industry.

This story first appeared on Medscape.com.

Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

There was a trend toward a greater risk of breast cancer with higher degrees of breast density asymmetry among women undergoing image-guided breast biopsies in a study presented at the AACR virtual meeting II.

The 854 women in the study had been referred for biopsy after an abnormal mammogram.

Researchers used the mammograms to assess global bilateral asymmetry, which was the overall absolute difference in percent fibroglandular tissue volume (%FGV) between the ipsilateral (biopsied) breast and the contralateral (unaffected) breast.

The researchers also assessed local bilateral asymmetry, which was the perilesional %FGV difference in an area twice the size of, but excluding, the biopsy target, and the corresponding area in the unaffected breast.

The women were then divided into quartiles based on breast density asymmetry.

Most of the women had benign breast disease, including proliferative (43%) and nonproliferative (33%) disease, but 23% had carcinoma in situ or invasive breast cancer.

The trend for higher risk of in situ or invasive cancer with increasing breast density asymmetry was observed only in the local analysis. The odds ratio was 1.59 (95% confidence interval, 0.94-2.69) for women in the highest quartile of breast density asymmetry (absolute difference, > 8.23) versus those in the lowest quartile (absolute difference, ≤ –5.55; P = .067).

When compared with women who had proliferative benign disease, women with carcinoma in situ or invasive breast cancer “were more likely to be in the higher than lower quartiles,” said lead investigator Maeve Mullooly, PhD, a research fellow at the Royal College of Surgeons in Dublin.

There was no association between breast density asymmetry and traditional breast cancer risk factors such as age, body mass index, race, and hormone therapy. However, among women diagnosed with benign nonproliferative disease, women with a breast cancer family history were more likely to have higher overall breast density asymmetry.
 

Study rationale and details

Higher breast density is a known risk factor for breast cancer. Breast asymmetry also has been reported as a possible risk factor (Breast Cancer Res. 2006;8[2]:R14), and incorporation of breast density asymmetry into traditional risk factors in one study improved risk prediction (Breast Cancer Res. 2017 Mar 14;19[1]:29).

Building on that work, the goal of Dr. Mullooly’s study was to “learn how to better use breast density to inform breast cancer risk prediction,” she said.

To that end, her team turned to 854 women enrolled from 2007-2010 in the National Cancer Institute’s Breast Radiology Evaluation and Study of Tissues Project, a cross-sectional molecular epidemiologic study designed to understand how breast density measures are related to breast cancer etiology.

Most of the women were non-Hispanic white. The mean age was 51 years (range, 40-65), and the median body mass index was ²⁵ kg/m².

About three-quarters of the women (76%) had a breast density asymmetry of at least 2% on the global analysis, with 43% having higher %FGV in the biopsied breast and 33% having higher %FGV in the unaffected breast. In all, 89% of women had local breast density asymmetry, with higher density in the biopsied breast in 61% of women and higher density in the contralateral breast in 28%.
 

Next steps

This research is ongoing, and additional follow-up is planned, according to Dr. Mullooly. She said the researchers hope to apply more recent analytical techniques to the mammograms and to study the histologic differences in their breast biopsy specimens, among other steps, to see if stronger relationships with greater clinical utility emerge.

It was a “very well done study” with “very provocative data,” said presentation moderator Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at the University of Texas MD Anderson Cancer Center in Houston.

She was interested in the planned next steps, particularly the histologic analysis of dense versus less dense breast tissue. There could be “differences in stroma or hormonal levels even at the microenvironmental level” that “represent a potential field defect, which later puts someone at risk,” she said, adding that it’s “great” that the work is continuing.

The National Cancer Institute funded the research. Dr. Mullooly reported no relevant disclosures. Dr. Wargo disclosed relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, GlaxoSmithKline, AstraZeneca, Imedex, Dava Oncology, Omniprex, Illumina, Gilead, PeerView, Physician Education Resource, MedImmune, Merck, Biothera Pharmaceuticals, and Microbiome DX.

aotto@mdedge.com

SOURCE: Mullooly M et al. AACR 2020, Abstract NG15.

There was a trend toward a greater risk of breast cancer with higher degrees of breast density asymmetry among women undergoing image-guided breast biopsies in a study presented at the AACR virtual meeting II.

The 854 women in the study had been referred for biopsy after an abnormal mammogram.

Researchers used the mammograms to assess global bilateral asymmetry, which was the overall absolute difference in percent fibroglandular tissue volume (%FGV) between the ipsilateral (biopsied) breast and the contralateral (unaffected) breast.

The researchers also assessed local bilateral asymmetry, which was the perilesional %FGV difference in an area twice the size of, but excluding, the biopsy target, and the corresponding area in the unaffected breast.

The women were then divided into quartiles based on breast density asymmetry.

Most of the women had benign breast disease, including proliferative (43%) and nonproliferative (33%) disease, but 23% had carcinoma in situ or invasive breast cancer.

The trend for higher risk of in situ or invasive cancer with increasing breast density asymmetry was observed only in the local analysis. The odds ratio was 1.59 (95% confidence interval, 0.94-2.69) for women in the highest quartile of breast density asymmetry (absolute difference, > 8.23) versus those in the lowest quartile (absolute difference, ≤ –5.55; P = .067).

When compared with women who had proliferative benign disease, women with carcinoma in situ or invasive breast cancer “were more likely to be in the higher than lower quartiles,” said lead investigator Maeve Mullooly, PhD, a research fellow at the Royal College of Surgeons in Dublin.

There was no association between breast density asymmetry and traditional breast cancer risk factors such as age, body mass index, race, and hormone therapy. However, among women diagnosed with benign nonproliferative disease, women with a breast cancer family history were more likely to have higher overall breast density asymmetry.
 

Study rationale and details

Higher breast density is a known risk factor for breast cancer. Breast asymmetry also has been reported as a possible risk factor (Breast Cancer Res. 2006;8[2]:R14), and incorporation of breast density asymmetry into traditional risk factors in one study improved risk prediction (Breast Cancer Res. 2017 Mar 14;19[1]:29).

Building on that work, the goal of Dr. Mullooly’s study was to “learn how to better use breast density to inform breast cancer risk prediction,” she said.

To that end, her team turned to 854 women enrolled from 2007-2010 in the National Cancer Institute’s Breast Radiology Evaluation and Study of Tissues Project, a cross-sectional molecular epidemiologic study designed to understand how breast density measures are related to breast cancer etiology.

Most of the women were non-Hispanic white. The mean age was 51 years (range, 40-65), and the median body mass index was ²⁵ kg/m².

About three-quarters of the women (76%) had a breast density asymmetry of at least 2% on the global analysis, with 43% having higher %FGV in the biopsied breast and 33% having higher %FGV in the unaffected breast. In all, 89% of women had local breast density asymmetry, with higher density in the biopsied breast in 61% of women and higher density in the contralateral breast in 28%.
 

Next steps

This research is ongoing, and additional follow-up is planned, according to Dr. Mullooly. She said the researchers hope to apply more recent analytical techniques to the mammograms and to study the histologic differences in their breast biopsy specimens, among other steps, to see if stronger relationships with greater clinical utility emerge.

It was a “very well done study” with “very provocative data,” said presentation moderator Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at the University of Texas MD Anderson Cancer Center in Houston.

She was interested in the planned next steps, particularly the histologic analysis of dense versus less dense breast tissue. There could be “differences in stroma or hormonal levels even at the microenvironmental level” that “represent a potential field defect, which later puts someone at risk,” she said, adding that it’s “great” that the work is continuing.

The National Cancer Institute funded the research. Dr. Mullooly reported no relevant disclosures. Dr. Wargo disclosed relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, GlaxoSmithKline, AstraZeneca, Imedex, Dava Oncology, Omniprex, Illumina, Gilead, PeerView, Physician Education Resource, MedImmune, Merck, Biothera Pharmaceuticals, and Microbiome DX.

aotto@mdedge.com

SOURCE: Mullooly M et al. AACR 2020, Abstract NG15.

There was a trend toward a greater risk of breast cancer with higher degrees of breast density asymmetry among women undergoing image-guided breast biopsies in a study presented at the AACR virtual meeting II.

The 854 women in the study had been referred for biopsy after an abnormal mammogram.

Researchers used the mammograms to assess global bilateral asymmetry, which was the overall absolute difference in percent fibroglandular tissue volume (%FGV) between the ipsilateral (biopsied) breast and the contralateral (unaffected) breast.

The researchers also assessed local bilateral asymmetry, which was the perilesional %FGV difference in an area twice the size of, but excluding, the biopsy target, and the corresponding area in the unaffected breast.

The women were then divided into quartiles based on breast density asymmetry.

Most of the women had benign breast disease, including proliferative (43%) and nonproliferative (33%) disease, but 23% had carcinoma in situ or invasive breast cancer.

The trend for higher risk of in situ or invasive cancer with increasing breast density asymmetry was observed only in the local analysis. The odds ratio was 1.59 (95% confidence interval, 0.94-2.69) for women in the highest quartile of breast density asymmetry (absolute difference, > 8.23) versus those in the lowest quartile (absolute difference, ≤ –5.55; P = .067).

When compared with women who had proliferative benign disease, women with carcinoma in situ or invasive breast cancer “were more likely to be in the higher than lower quartiles,” said lead investigator Maeve Mullooly, PhD, a research fellow at the Royal College of Surgeons in Dublin.

There was no association between breast density asymmetry and traditional breast cancer risk factors such as age, body mass index, race, and hormone therapy. However, among women diagnosed with benign nonproliferative disease, women with a breast cancer family history were more likely to have higher overall breast density asymmetry.
 

Study rationale and details

Higher breast density is a known risk factor for breast cancer. Breast asymmetry also has been reported as a possible risk factor (Breast Cancer Res. 2006;8[2]:R14), and incorporation of breast density asymmetry into traditional risk factors in one study improved risk prediction (Breast Cancer Res. 2017 Mar 14;19[1]:29).

Building on that work, the goal of Dr. Mullooly’s study was to “learn how to better use breast density to inform breast cancer risk prediction,” she said.

To that end, her team turned to 854 women enrolled from 2007-2010 in the National Cancer Institute’s Breast Radiology Evaluation and Study of Tissues Project, a cross-sectional molecular epidemiologic study designed to understand how breast density measures are related to breast cancer etiology.

Most of the women were non-Hispanic white. The mean age was 51 years (range, 40-65), and the median body mass index was ²⁵ kg/m².

About three-quarters of the women (76%) had a breast density asymmetry of at least 2% on the global analysis, with 43% having higher %FGV in the biopsied breast and 33% having higher %FGV in the unaffected breast. In all, 89% of women had local breast density asymmetry, with higher density in the biopsied breast in 61% of women and higher density in the contralateral breast in 28%.
 

Next steps

This research is ongoing, and additional follow-up is planned, according to Dr. Mullooly. She said the researchers hope to apply more recent analytical techniques to the mammograms and to study the histologic differences in their breast biopsy specimens, among other steps, to see if stronger relationships with greater clinical utility emerge.

It was a “very well done study” with “very provocative data,” said presentation moderator Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at the University of Texas MD Anderson Cancer Center in Houston.

She was interested in the planned next steps, particularly the histologic analysis of dense versus less dense breast tissue. There could be “differences in stroma or hormonal levels even at the microenvironmental level” that “represent a potential field defect, which later puts someone at risk,” she said, adding that it’s “great” that the work is continuing.

The National Cancer Institute funded the research. Dr. Mullooly reported no relevant disclosures. Dr. Wargo disclosed relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, GlaxoSmithKline, AstraZeneca, Imedex, Dava Oncology, Omniprex, Illumina, Gilead, PeerView, Physician Education Resource, MedImmune, Merck, Biothera Pharmaceuticals, and Microbiome DX.

aotto@mdedge.com

SOURCE: Mullooly M et al. AACR 2020, Abstract NG15.

Here are the stories our MDedge editors across specialties think you need to know about today:

Lifestyle choices may reduce breast cancer risk regardless of genetics

A “favorable” lifestyle was associated with a reduced risk of breast cancer even among women at high genetic risk for the disease in a study of more than 90,000 women, researchers reported.

The findings suggest that, regardless of genetic risk, women may be able to reduce their risk of developing breast cancer by getting adequate levels of exercise; maintaining a healthy weight; and limiting or eliminating use of alcohol, oral contraceptives, and hormone replacement therapy.

“These data should empower patients that they can impact on their overall health and reduce the risk of developing breast cancer,” said William Gradishar, MD, who was not invovled with the study. Read more.

Primary care practices may lose $68K per physician this year

Primary care practices stand to lose almost $68,000 per full-time physician this year as COVID-19 causes care delays and cancellations, researchers estimate. And while some outpatient care has started to rebound to near baseline appointment levels, other ambulatory specialties remain dramatically down from prepandemic rates.

Dermatology and rheumatology visits have recovered, but some specialties have cumulative deficits that are particularly concerning. For example, pediatric visits were down by 47% in the 3 months since March 15, and pulmonology visits were down 45% in that time.

This primary care estimate is without a potential second wave of COVID-19, noted Sanjay Basu, MD, director of research and population health at Collective Health in San Francisco, and colleagues.

“We expect ongoing turbulent times, so having a prospective payment could unleash the capacity for primary care practices to be creative in the way they care for their patients,” Daniel Horn, MD, director of population health and quality at Massachusetts General Hospital in Boston, said in an interview. Read more.

Big pharma sues to block Minnesota insulin affordability law

The Pharmaceutical Research and Manufacturers Association (PhRMA) is suing the state of Minnesota in an attempt to overturn a law that requires insulin makers to provide an emergency supply to individuals free of charge.

In the July 1 filing, PhRMA’s attorneys said the law is unconstitutional. It “order[s] pharmaceutical manufacturers to give insulin to state residents, on the state’s prescribed terms, at no charge to the recipients and without compensating the manufacturers in any way.”

The state has estimated that as many as 30,000 Minnesotans would be eligible for free insulin in the first year of the program. The drugmakers strenuously objected, noting that would mean they would “be compelled to provide 173,800 monthly supplies of free insulin” just in the first year.

“There is nothing in the U.S. Constitution that prevents states from saving the lives of its citizens who are in imminent danger,” said Mayo Clinic hematologist S. Vincent Rajkumar, MD. “The only motives for this lawsuit in my opinion are greed and the worry that other states may also choose to put lives of patients ahead of pharma profits.” Read more.

Despite guidelines, kids get opioids & steroids for pneumonia, sinusitis

A significant percentage of children receive opioids and systemic corticosteroids for pneumonia and sinusitis despite guidelines, according to an analysis of 2016 Medicaid data from South Carolina.

Prescriptions for these drugs were more likely after visits to EDs than after ambulatory visits, researchers reported in Pediatrics.

“Each of the 828 opioid and 2,737 systemic steroid prescriptions in the data set represent a potentially inappropriate prescription,” wrote Karina G. Phang, MD, MPH, of Geisinger Medical Center in Danville, Pa., and colleagues. “These rates appear excessive given that the use of these medications is not supported by available research or recommended in national guidelines.” Read more.

Study supports changing classification of RCC

The definition of stage IV renal cell carcinoma (RCC) should be expanded to include lymph node–positive stage III disease, according to a population-level cohort study published in Cancer.

While patients with lymph node–negative stage III disease had superior overall survival at 5 years, survival rates were similar between patients with node–positive stage III disease and stage IV disease. This supports reclassifying stage III node-positive RCC to stage IV, according to researchers.

“Prior institutional studies have indicated that, among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease,” wrote Arnav Srivastava, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and colleagues. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Lifestyle choices may reduce breast cancer risk regardless of genetics

A “favorable” lifestyle was associated with a reduced risk of breast cancer even among women at high genetic risk for the disease in a study of more than 90,000 women, researchers reported.

The findings suggest that, regardless of genetic risk, women may be able to reduce their risk of developing breast cancer by getting adequate levels of exercise; maintaining a healthy weight; and limiting or eliminating use of alcohol, oral contraceptives, and hormone replacement therapy.

“These data should empower patients that they can impact on their overall health and reduce the risk of developing breast cancer,” said William Gradishar, MD, who was not invovled with the study. Read more.

Primary care practices may lose $68K per physician this year

Primary care practices stand to lose almost $68,000 per full-time physician this year as COVID-19 causes care delays and cancellations, researchers estimate. And while some outpatient care has started to rebound to near baseline appointment levels, other ambulatory specialties remain dramatically down from prepandemic rates.

Dermatology and rheumatology visits have recovered, but some specialties have cumulative deficits that are particularly concerning. For example, pediatric visits were down by 47% in the 3 months since March 15, and pulmonology visits were down 45% in that time.

This primary care estimate is without a potential second wave of COVID-19, noted Sanjay Basu, MD, director of research and population health at Collective Health in San Francisco, and colleagues.

“We expect ongoing turbulent times, so having a prospective payment could unleash the capacity for primary care practices to be creative in the way they care for their patients,” Daniel Horn, MD, director of population health and quality at Massachusetts General Hospital in Boston, said in an interview. Read more.

Big pharma sues to block Minnesota insulin affordability law

The Pharmaceutical Research and Manufacturers Association (PhRMA) is suing the state of Minnesota in an attempt to overturn a law that requires insulin makers to provide an emergency supply to individuals free of charge.

In the July 1 filing, PhRMA’s attorneys said the law is unconstitutional. It “order[s] pharmaceutical manufacturers to give insulin to state residents, on the state’s prescribed terms, at no charge to the recipients and without compensating the manufacturers in any way.”

The state has estimated that as many as 30,000 Minnesotans would be eligible for free insulin in the first year of the program. The drugmakers strenuously objected, noting that would mean they would “be compelled to provide 173,800 monthly supplies of free insulin” just in the first year.

“There is nothing in the U.S. Constitution that prevents states from saving the lives of its citizens who are in imminent danger,” said Mayo Clinic hematologist S. Vincent Rajkumar, MD. “The only motives for this lawsuit in my opinion are greed and the worry that other states may also choose to put lives of patients ahead of pharma profits.” Read more.

Despite guidelines, kids get opioids & steroids for pneumonia, sinusitis

A significant percentage of children receive opioids and systemic corticosteroids for pneumonia and sinusitis despite guidelines, according to an analysis of 2016 Medicaid data from South Carolina.

Prescriptions for these drugs were more likely after visits to EDs than after ambulatory visits, researchers reported in Pediatrics.

“Each of the 828 opioid and 2,737 systemic steroid prescriptions in the data set represent a potentially inappropriate prescription,” wrote Karina G. Phang, MD, MPH, of Geisinger Medical Center in Danville, Pa., and colleagues. “These rates appear excessive given that the use of these medications is not supported by available research or recommended in national guidelines.” Read more.

Study supports changing classification of RCC

The definition of stage IV renal cell carcinoma (RCC) should be expanded to include lymph node–positive stage III disease, according to a population-level cohort study published in Cancer.

While patients with lymph node–negative stage III disease had superior overall survival at 5 years, survival rates were similar between patients with node–positive stage III disease and stage IV disease. This supports reclassifying stage III node-positive RCC to stage IV, according to researchers.

“Prior institutional studies have indicated that, among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease,” wrote Arnav Srivastava, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and colleagues. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Lifestyle choices may reduce breast cancer risk regardless of genetics

A “favorable” lifestyle was associated with a reduced risk of breast cancer even among women at high genetic risk for the disease in a study of more than 90,000 women, researchers reported.

The findings suggest that, regardless of genetic risk, women may be able to reduce their risk of developing breast cancer by getting adequate levels of exercise; maintaining a healthy weight; and limiting or eliminating use of alcohol, oral contraceptives, and hormone replacement therapy.

“These data should empower patients that they can impact on their overall health and reduce the risk of developing breast cancer,” said William Gradishar, MD, who was not invovled with the study. Read more.

Primary care practices may lose $68K per physician this year

Primary care practices stand to lose almost $68,000 per full-time physician this year as COVID-19 causes care delays and cancellations, researchers estimate. And while some outpatient care has started to rebound to near baseline appointment levels, other ambulatory specialties remain dramatically down from prepandemic rates.

Dermatology and rheumatology visits have recovered, but some specialties have cumulative deficits that are particularly concerning. For example, pediatric visits were down by 47% in the 3 months since March 15, and pulmonology visits were down 45% in that time.

This primary care estimate is without a potential second wave of COVID-19, noted Sanjay Basu, MD, director of research and population health at Collective Health in San Francisco, and colleagues.

“We expect ongoing turbulent times, so having a prospective payment could unleash the capacity for primary care practices to be creative in the way they care for their patients,” Daniel Horn, MD, director of population health and quality at Massachusetts General Hospital in Boston, said in an interview. Read more.

Big pharma sues to block Minnesota insulin affordability law

The Pharmaceutical Research and Manufacturers Association (PhRMA) is suing the state of Minnesota in an attempt to overturn a law that requires insulin makers to provide an emergency supply to individuals free of charge.

In the July 1 filing, PhRMA’s attorneys said the law is unconstitutional. It “order[s] pharmaceutical manufacturers to give insulin to state residents, on the state’s prescribed terms, at no charge to the recipients and without compensating the manufacturers in any way.”

The state has estimated that as many as 30,000 Minnesotans would be eligible for free insulin in the first year of the program. The drugmakers strenuously objected, noting that would mean they would “be compelled to provide 173,800 monthly supplies of free insulin” just in the first year.

“There is nothing in the U.S. Constitution that prevents states from saving the lives of its citizens who are in imminent danger,” said Mayo Clinic hematologist S. Vincent Rajkumar, MD. “The only motives for this lawsuit in my opinion are greed and the worry that other states may also choose to put lives of patients ahead of pharma profits.” Read more.

Despite guidelines, kids get opioids & steroids for pneumonia, sinusitis

A significant percentage of children receive opioids and systemic corticosteroids for pneumonia and sinusitis despite guidelines, according to an analysis of 2016 Medicaid data from South Carolina.

Prescriptions for these drugs were more likely after visits to EDs than after ambulatory visits, researchers reported in Pediatrics.

“Each of the 828 opioid and 2,737 systemic steroid prescriptions in the data set represent a potentially inappropriate prescription,” wrote Karina G. Phang, MD, MPH, of Geisinger Medical Center in Danville, Pa., and colleagues. “These rates appear excessive given that the use of these medications is not supported by available research or recommended in national guidelines.” Read more.

Study supports changing classification of RCC

The definition of stage IV renal cell carcinoma (RCC) should be expanded to include lymph node–positive stage III disease, according to a population-level cohort study published in Cancer.

While patients with lymph node–negative stage III disease had superior overall survival at 5 years, survival rates were similar between patients with node–positive stage III disease and stage IV disease. This supports reclassifying stage III node-positive RCC to stage IV, according to researchers.

“Prior institutional studies have indicated that, among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease,” wrote Arnav Srivastava, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and colleagues. Read more.

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