Breast Cancer

Regional nodal irradiation added to whole-breast or thoracic wall irradiation in an unselected patient population reduces breast cancer recurrence rates and improves disease-free and distant disease-free survival, but has little or no effect on overall survival, results of two large, long-term, randomized clinical trials show.

In the MA.20 trial, there was no significant difference in overall survival at 10-year follow-up between women with early breast cancer treated with breast-conserving surgery, adjuvant systemic therapy, and whole-breast irradiation with or without regional nodal irradiation.

Women who received nodal irradiation had significantly better disease-free survival, but at the cost of higher rates of pneumonitis and lymphedema, report Dr. Timothy J. Whelan from the Juravinski Cancer Centre at Hamilton Health Sciences in Hamilton, Ont., and his colleagues in the July 23 issue of the New England Journal of Medicine (doi:10.1056/NEJMoa1415340).

In the EORTC 22922/10925 study, investigators in the European Organization for Research and Treatment of Cancer randomly assigned women with a centrally or medially located primary tumor irrespective of axillary involvement, or an externally located tumor with axillary involvement, to receive either whole-breast or thoracic wall irradiation alone, or with the addition of regional nodal irradiation.

As in the Canadian study, the investigators found no difference in overall survival at 10 years between women who received nodal irradiation and those who did not. Similarly, the EORTC investigators found that rates of disease-free survival and distant disease-free survival were better among women who received nodal irradiation. The nodal irradiation group also had a significantly lower rate of breast cancer–specific death. The European investigators, however, felt that “the acute side effects of regional nodal irradiation were modest.” The study, by Dr. Philip M. Poortmans of Radboud University in Nijmegen, the Netherlands, also appears in the New England Journal of Medicine (2015 July 23 [doi:10.1056/NEJMoa1415369]).

“The trials by Whelan et al. and Poortmans et al. show the possibilities and the limits of more extensive regional treatment of breast cancer in an unselected population and frame the discussion for the next generation of individualized treatment programs, built largely on genomic characterization of tumor biology,” write Dr. Harold J. Burstein of the Dana-Farber Cancer Institute in Boston and Dr. Monica Morrow of the Memorial Sloan Kettering Cancer in New York, in an accompanying editorial.

MA.20

From March 2000 through February 2007, Dr. Whelan and colleagues in the MA.20 trial enrolled 1,832 women with node-positive or high-risk node-negative cancer treated with breast-conserving surgery and adjuvant systemic therapy. The women were randomly assigned, 916 in each group, to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph node), or whole-breast irradiation alone (controls).

At 10-year follow-up, overall survival rates were similar, at 82.8% in the nodal irradiation group and 81.8% in the control group (hazard ratio, 0.91, P =.38). However, as noted before, the rate of disease-free survival was 82% in the nodal irradiation group, compared with 77% in the control group (HR, 0.76, P = .01).

When they looked at adverse effects of the additional radiation, however, the investigators found that rates of grade 2 or greater acute pneumonitis were 1.2% among nodal irradiation patients, compared with just 0.2% of controls (P = .001). Lymphedema rates were also nearly twice as high among nodally irradiated patients (8.4% vs. 4.5%, respectively, P = .001).

The authors concluded that the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery in women with node-positive or high-risk node-negative breast cancer did not improve overall survival but did reduce breast-cancer recurrence. “Our findings indicate the importance of basing treatment decisions on a careful discussion of the potential benefits and risks with each patient,” they wrote.

EORTC 22922/10925

In this trial, a total of 4004 women were randomized from 1996 through 2004. The patients had either centrally or medially located primary tumors, irrespective of axillary involvement, or an externally located tumor with axillary involvement.

Most of the women (76.1%) had breast-conserving surgery. Of those who underwent radical mastectomy 73.4% of the patients in both the nodal irradiation and control groups underwent chest wall irradiation.

All but 1% of patients with node-positive disease received adjuvant systemic therapy, as did 66.3% of patients with node-negative disease.

At 10 years, overall survival was not significantly different between the two groups, at 82.3% in the nodal irradiation group and 80.7% in the control group (HR, 0.87; P = 0.06).

As in the Canadian trial, the rate of disease-free survival was significantly better among patients who received nodal-irradiation, at 72.1% vs. 69.1% (HR for disease progression or death, 0.89; P = .04).

Regional nodal irradiation was also associated with significantly better distant disease-free survival (78.0% vs. 75.0%; HR, 0.86; P = .02), and breast cancer mortality (12.5% vs.14.4%; HR, 0.82; P = .02).

The rate of pulmonary fibrosis at 10 years was higher among patients in the nodal irradiation group (4.4% vs. 1.7%, P < .001). Rates of cardiac fibrosis and cardiac disease were also numerically but not significantly higher among patients who received nodal irradiation. There were no other significant differences between the groups in other late toxic effects or performance status, the authors reported.

“Our data do not apply to patients with lateral node-negative cancers, which is the largest patient subgroup in industrialized countries,” they noted.

The MA.20 study was supported by grants from the Canadian Cancer Society Research Institute, NCIC Clinical Trials Group, Canadian Breast Cancer Research Initiative, U.S. National Cancer Institute, and the Cancer Council of Victoria, New South Wales, Queensland, and South Australia. Dr. Whelan reported receiving fees for serving on an advisory board from Genomic Health and testing reagents for another study from NanoString Technologies. The EORTC study was supported by the EORTC and national health agencies. Dr. Poortmans reported no conflicts of interest. Dr. Burstein reported no conflicts of interest. Dr. Morrow reported personal fees from Genomic Health outside the submitted work.

Regional nodal irradiation added to whole-breast or thoracic wall irradiation in an unselected patient population reduces breast cancer recurrence rates and improves disease-free and distant disease-free survival, but has little or no effect on overall survival, results of two large, long-term, randomized clinical trials show.

In the MA.20 trial, there was no significant difference in overall survival at 10-year follow-up between women with early breast cancer treated with breast-conserving surgery, adjuvant systemic therapy, and whole-breast irradiation with or without regional nodal irradiation.

Women who received nodal irradiation had significantly better disease-free survival, but at the cost of higher rates of pneumonitis and lymphedema, report Dr. Timothy J. Whelan from the Juravinski Cancer Centre at Hamilton Health Sciences in Hamilton, Ont., and his colleagues in the July 23 issue of the New England Journal of Medicine (doi:10.1056/NEJMoa1415340).

In the EORTC 22922/10925 study, investigators in the European Organization for Research and Treatment of Cancer randomly assigned women with a centrally or medially located primary tumor irrespective of axillary involvement, or an externally located tumor with axillary involvement, to receive either whole-breast or thoracic wall irradiation alone, or with the addition of regional nodal irradiation.

As in the Canadian study, the investigators found no difference in overall survival at 10 years between women who received nodal irradiation and those who did not. Similarly, the EORTC investigators found that rates of disease-free survival and distant disease-free survival were better among women who received nodal irradiation. The nodal irradiation group also had a significantly lower rate of breast cancer–specific death. The European investigators, however, felt that “the acute side effects of regional nodal irradiation were modest.” The study, by Dr. Philip M. Poortmans of Radboud University in Nijmegen, the Netherlands, also appears in the New England Journal of Medicine (2015 July 23 [doi:10.1056/NEJMoa1415369]).

“The trials by Whelan et al. and Poortmans et al. show the possibilities and the limits of more extensive regional treatment of breast cancer in an unselected population and frame the discussion for the next generation of individualized treatment programs, built largely on genomic characterization of tumor biology,” write Dr. Harold J. Burstein of the Dana-Farber Cancer Institute in Boston and Dr. Monica Morrow of the Memorial Sloan Kettering Cancer in New York, in an accompanying editorial.

MA.20

From March 2000 through February 2007, Dr. Whelan and colleagues in the MA.20 trial enrolled 1,832 women with node-positive or high-risk node-negative cancer treated with breast-conserving surgery and adjuvant systemic therapy. The women were randomly assigned, 916 in each group, to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph node), or whole-breast irradiation alone (controls).

At 10-year follow-up, overall survival rates were similar, at 82.8% in the nodal irradiation group and 81.8% in the control group (hazard ratio, 0.91, P =.38). However, as noted before, the rate of disease-free survival was 82% in the nodal irradiation group, compared with 77% in the control group (HR, 0.76, P = .01).

When they looked at adverse effects of the additional radiation, however, the investigators found that rates of grade 2 or greater acute pneumonitis were 1.2% among nodal irradiation patients, compared with just 0.2% of controls (P = .001). Lymphedema rates were also nearly twice as high among nodally irradiated patients (8.4% vs. 4.5%, respectively, P = .001).

The authors concluded that the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery in women with node-positive or high-risk node-negative breast cancer did not improve overall survival but did reduce breast-cancer recurrence. “Our findings indicate the importance of basing treatment decisions on a careful discussion of the potential benefits and risks with each patient,” they wrote.

EORTC 22922/10925

In this trial, a total of 4004 women were randomized from 1996 through 2004. The patients had either centrally or medially located primary tumors, irrespective of axillary involvement, or an externally located tumor with axillary involvement.

Most of the women (76.1%) had breast-conserving surgery. Of those who underwent radical mastectomy 73.4% of the patients in both the nodal irradiation and control groups underwent chest wall irradiation.

All but 1% of patients with node-positive disease received adjuvant systemic therapy, as did 66.3% of patients with node-negative disease.

At 10 years, overall survival was not significantly different between the two groups, at 82.3% in the nodal irradiation group and 80.7% in the control group (HR, 0.87; P = 0.06).

As in the Canadian trial, the rate of disease-free survival was significantly better among patients who received nodal-irradiation, at 72.1% vs. 69.1% (HR for disease progression or death, 0.89; P = .04).

Regional nodal irradiation was also associated with significantly better distant disease-free survival (78.0% vs. 75.0%; HR, 0.86; P = .02), and breast cancer mortality (12.5% vs.14.4%; HR, 0.82; P = .02).

The rate of pulmonary fibrosis at 10 years was higher among patients in the nodal irradiation group (4.4% vs. 1.7%, P < .001). Rates of cardiac fibrosis and cardiac disease were also numerically but not significantly higher among patients who received nodal irradiation. There were no other significant differences between the groups in other late toxic effects or performance status, the authors reported.

“Our data do not apply to patients with lateral node-negative cancers, which is the largest patient subgroup in industrialized countries,” they noted.

The MA.20 study was supported by grants from the Canadian Cancer Society Research Institute, NCIC Clinical Trials Group, Canadian Breast Cancer Research Initiative, U.S. National Cancer Institute, and the Cancer Council of Victoria, New South Wales, Queensland, and South Australia. Dr. Whelan reported receiving fees for serving on an advisory board from Genomic Health and testing reagents for another study from NanoString Technologies. The EORTC study was supported by the EORTC and national health agencies. Dr. Poortmans reported no conflicts of interest. Dr. Burstein reported no conflicts of interest. Dr. Morrow reported personal fees from Genomic Health outside the submitted work.

Regional nodal irradiation added to whole-breast or thoracic wall irradiation in an unselected patient population reduces breast cancer recurrence rates and improves disease-free and distant disease-free survival, but has little or no effect on overall survival, results of two large, long-term, randomized clinical trials show.

In the MA.20 trial, there was no significant difference in overall survival at 10-year follow-up between women with early breast cancer treated with breast-conserving surgery, adjuvant systemic therapy, and whole-breast irradiation with or without regional nodal irradiation.

Women who received nodal irradiation had significantly better disease-free survival, but at the cost of higher rates of pneumonitis and lymphedema, report Dr. Timothy J. Whelan from the Juravinski Cancer Centre at Hamilton Health Sciences in Hamilton, Ont., and his colleagues in the July 23 issue of the New England Journal of Medicine (doi:10.1056/NEJMoa1415340).

In the EORTC 22922/10925 study, investigators in the European Organization for Research and Treatment of Cancer randomly assigned women with a centrally or medially located primary tumor irrespective of axillary involvement, or an externally located tumor with axillary involvement, to receive either whole-breast or thoracic wall irradiation alone, or with the addition of regional nodal irradiation.

As in the Canadian study, the investigators found no difference in overall survival at 10 years between women who received nodal irradiation and those who did not. Similarly, the EORTC investigators found that rates of disease-free survival and distant disease-free survival were better among women who received nodal irradiation. The nodal irradiation group also had a significantly lower rate of breast cancer–specific death. The European investigators, however, felt that “the acute side effects of regional nodal irradiation were modest.” The study, by Dr. Philip M. Poortmans of Radboud University in Nijmegen, the Netherlands, also appears in the New England Journal of Medicine (2015 July 23 [doi:10.1056/NEJMoa1415369]).

“The trials by Whelan et al. and Poortmans et al. show the possibilities and the limits of more extensive regional treatment of breast cancer in an unselected population and frame the discussion for the next generation of individualized treatment programs, built largely on genomic characterization of tumor biology,” write Dr. Harold J. Burstein of the Dana-Farber Cancer Institute in Boston and Dr. Monica Morrow of the Memorial Sloan Kettering Cancer in New York, in an accompanying editorial.

MA.20

From March 2000 through February 2007, Dr. Whelan and colleagues in the MA.20 trial enrolled 1,832 women with node-positive or high-risk node-negative cancer treated with breast-conserving surgery and adjuvant systemic therapy. The women were randomly assigned, 916 in each group, to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph node), or whole-breast irradiation alone (controls).

At 10-year follow-up, overall survival rates were similar, at 82.8% in the nodal irradiation group and 81.8% in the control group (hazard ratio, 0.91, P =.38). However, as noted before, the rate of disease-free survival was 82% in the nodal irradiation group, compared with 77% in the control group (HR, 0.76, P = .01).

When they looked at adverse effects of the additional radiation, however, the investigators found that rates of grade 2 or greater acute pneumonitis were 1.2% among nodal irradiation patients, compared with just 0.2% of controls (P = .001). Lymphedema rates were also nearly twice as high among nodally irradiated patients (8.4% vs. 4.5%, respectively, P = .001).

The authors concluded that the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery in women with node-positive or high-risk node-negative breast cancer did not improve overall survival but did reduce breast-cancer recurrence. “Our findings indicate the importance of basing treatment decisions on a careful discussion of the potential benefits and risks with each patient,” they wrote.

EORTC 22922/10925

In this trial, a total of 4004 women were randomized from 1996 through 2004. The patients had either centrally or medially located primary tumors, irrespective of axillary involvement, or an externally located tumor with axillary involvement.

Most of the women (76.1%) had breast-conserving surgery. Of those who underwent radical mastectomy 73.4% of the patients in both the nodal irradiation and control groups underwent chest wall irradiation.

All but 1% of patients with node-positive disease received adjuvant systemic therapy, as did 66.3% of patients with node-negative disease.

At 10 years, overall survival was not significantly different between the two groups, at 82.3% in the nodal irradiation group and 80.7% in the control group (HR, 0.87; P = 0.06).

As in the Canadian trial, the rate of disease-free survival was significantly better among patients who received nodal-irradiation, at 72.1% vs. 69.1% (HR for disease progression or death, 0.89; P = .04).

Regional nodal irradiation was also associated with significantly better distant disease-free survival (78.0% vs. 75.0%; HR, 0.86; P = .02), and breast cancer mortality (12.5% vs.14.4%; HR, 0.82; P = .02).

The rate of pulmonary fibrosis at 10 years was higher among patients in the nodal irradiation group (4.4% vs. 1.7%, P < .001). Rates of cardiac fibrosis and cardiac disease were also numerically but not significantly higher among patients who received nodal irradiation. There were no other significant differences between the groups in other late toxic effects or performance status, the authors reported.

“Our data do not apply to patients with lateral node-negative cancers, which is the largest patient subgroup in industrialized countries,” they noted.

The MA.20 study was supported by grants from the Canadian Cancer Society Research Institute, NCIC Clinical Trials Group, Canadian Breast Cancer Research Initiative, U.S. National Cancer Institute, and the Cancer Council of Victoria, New South Wales, Queensland, and South Australia. Dr. Whelan reported receiving fees for serving on an advisory board from Genomic Health and testing reagents for another study from NanoString Technologies. The EORTC study was supported by the EORTC and national health agencies. Dr. Poortmans reported no conflicts of interest. Dr. Burstein reported no conflicts of interest. Dr. Morrow reported personal fees from Genomic Health outside the submitted work.

Breast cancer is the most frequently diagnosed cancer in women, with an estimated 231,840 new cases representing 14.0% of all new cancer cases in the United States in 2015.¹ Early screening and modern techniques of imaging and diagnosis have led to a significant improvement in detecting early-stage breast cancers and to a decrease in the incidence of metastatic breast cancer (MBC).² About 20%-30% of patients who are initially diagnosed with an early-stage, nonmetastatic breast cancer will subsequently develop a distant metastatic disease. Between 6%-10% of the new breast cancer cases present initially as stage IV, referred to as de novo MBC.

Click on the PDF icon at the top of this introduction to read the full article.

Breast cancer is the most frequently diagnosed cancer in women, with an estimated 231,840 new cases representing 14.0% of all new cancer cases in the United States in 2015.¹ Early screening and modern techniques of imaging and diagnosis have led to a significant improvement in detecting early-stage breast cancers and to a decrease in the incidence of metastatic breast cancer (MBC).² About 20%-30% of patients who are initially diagnosed with an early-stage, nonmetastatic breast cancer will subsequently develop a distant metastatic disease. Between 6%-10% of the new breast cancer cases present initially as stage IV, referred to as de novo MBC.

Click on the PDF icon at the top of this introduction to read the full article.

Breast cancer is the most frequently diagnosed cancer in women, with an estimated 231,840 new cases representing 14.0% of all new cancer cases in the United States in 2015.¹ Early screening and modern techniques of imaging and diagnosis have led to a significant improvement in detecting early-stage breast cancers and to a decrease in the incidence of metastatic breast cancer (MBC).² About 20%-30% of patients who are initially diagnosed with an early-stage, nonmetastatic breast cancer will subsequently develop a distant metastatic disease. Between 6%-10% of the new breast cancer cases present initially as stage IV, referred to as de novo MBC.

Click on the PDF icon at the top of this introduction to read the full article.

Radioactive iodine (RAI) therapy in thyroid cancer patients does not cause such patients to get breast cancer, suggests a retrospective study of female patients from Seoul National University Hospital in South Korea.

The study enrolled 6,150 patients with thyroid cancer between 1973 and 2009, who were followed until December 2012. Of the sample, 3.691 (59%) received RAI therapy, and 99 were diagnosed with primary breast cancers during the follow-up period.

The study showed that RAI therapy did not significantly increase the incidence of breast cancer subsequent to diagnosis of thyroid cancer among patients, when a 2-year latency period was accounted for. An additional finding was that the numbers of breast cancer diagnoses made during the follow-up period for those study participants who received high doses of RAI therapy (greater than or equal to 120 mCi) and those patients who did not receive any RAI therapy were not significantly different from each other.

“The results from our study based on a large cohort of thyroid cancer patients clearly demonstrated that RAI treatment in these patients did not increase the risk of development nor worsen the recurrence of breast cancer,” Dr. Hwa Young Ahn of the department of internal medicine at Seoul National University, South Korea, and Hye Sook Min, and associates.

Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2014-2896).

This study was supported by research grants from the Korean Foundation for Cancer Research, Seoul National University Bundang Hospital Research Grants, and the Education and Research Encouragement Fund of Seoul National University Hospital. The investigators reported having no financial conflicts of interest.

klennon@frontlinemedicalnews.com

Radioactive iodine (RAI) therapy in thyroid cancer patients does not cause such patients to get breast cancer, suggests a retrospective study of female patients from Seoul National University Hospital in South Korea.

The study enrolled 6,150 patients with thyroid cancer between 1973 and 2009, who were followed until December 2012. Of the sample, 3.691 (59%) received RAI therapy, and 99 were diagnosed with primary breast cancers during the follow-up period.

The study showed that RAI therapy did not significantly increase the incidence of breast cancer subsequent to diagnosis of thyroid cancer among patients, when a 2-year latency period was accounted for. An additional finding was that the numbers of breast cancer diagnoses made during the follow-up period for those study participants who received high doses of RAI therapy (greater than or equal to 120 mCi) and those patients who did not receive any RAI therapy were not significantly different from each other.

“The results from our study based on a large cohort of thyroid cancer patients clearly demonstrated that RAI treatment in these patients did not increase the risk of development nor worsen the recurrence of breast cancer,” Dr. Hwa Young Ahn of the department of internal medicine at Seoul National University, South Korea, and Hye Sook Min, and associates.

Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2014-2896).

This study was supported by research grants from the Korean Foundation for Cancer Research, Seoul National University Bundang Hospital Research Grants, and the Education and Research Encouragement Fund of Seoul National University Hospital. The investigators reported having no financial conflicts of interest.

klennon@frontlinemedicalnews.com

Radioactive iodine (RAI) therapy in thyroid cancer patients does not cause such patients to get breast cancer, suggests a retrospective study of female patients from Seoul National University Hospital in South Korea.

The study enrolled 6,150 patients with thyroid cancer between 1973 and 2009, who were followed until December 2012. Of the sample, 3.691 (59%) received RAI therapy, and 99 were diagnosed with primary breast cancers during the follow-up period.

The study showed that RAI therapy did not significantly increase the incidence of breast cancer subsequent to diagnosis of thyroid cancer among patients, when a 2-year latency period was accounted for. An additional finding was that the numbers of breast cancer diagnoses made during the follow-up period for those study participants who received high doses of RAI therapy (greater than or equal to 120 mCi) and those patients who did not receive any RAI therapy were not significantly different from each other.

“The results from our study based on a large cohort of thyroid cancer patients clearly demonstrated that RAI treatment in these patients did not increase the risk of development nor worsen the recurrence of breast cancer,” Dr. Hwa Young Ahn of the department of internal medicine at Seoul National University, South Korea, and Hye Sook Min, and associates.

Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2014-2896).

This study was supported by research grants from the Korean Foundation for Cancer Research, Seoul National University Bundang Hospital Research Grants, and the Education and Research Encouragement Fund of Seoul National University Hospital. The investigators reported having no financial conflicts of interest.

klennon@frontlinemedicalnews.com

In regions where more women undergo screening mammography, the detection of small cancers increases but mortality doesn’t change significantly, compared with regions where fewer women have the screening, according to a report published July 6 in JAMA Internal Medicine.

The finding indicates that screening mammography leads to “widespread overdiagnosis,” identifying many small, indolent, or regressive breast tumors that otherwise would not have become clinically apparent, reported Charles Harding, a data scientist and statistical analyst in Seattle, and his associates.

Ideally, screening mammography should result in increased detection of small (less advanced) cancers, decreased detection of large (more advanced) cancers, and reduced breast cancer–specific mortality. To examine whether this is what actually happens, Mr. Harding and his colleagues analyzed mammography rates among 16,120,349 women over age 40 residing in 547 counties across the country during a 1-year period, where the frequency of screening ranged from 39% to 78%.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

They correlated these findings with breast cancer incidence and mortality data in those regions for the ensuing 10 years. They identified 53,207 incident cases of breast cancer for their primary analysis.

There was a clear correlation between the number of users of screening mammography and breast cancer incidence. A 10% increase in screening was associated with a 16% mean increase in breast cancer incidence (relative risk, 1.16), or an absolute increase of 35-49 cases per 100,000. However, there was no significant change in breast cancer mortality (RR, 1.01).

When the data were stratified according to tumor size, the researchers found that the increase in breast cancer was confined to small tumors only (2 cm or less).

Moreover, “although it has been hoped that screening would allow breast-conserving surgical procedures to replace more extensive mastectomies, we saw no evidence supporting this change,” the investigators wrote (JAMA Intern. Med. 2015 July 6 [doi:10.1001/jamainternmed.2015.3043]).

Future research should focus on whether all women undergoing screening mammography have the same risk of overdiagnosis, or if overdiagnosis is more likely to occur in certain groups, Mr. Harding and his associates added.

Mr. Harding reported receiving funding from Exergen Corporation for this work. Another study author, Francesco Pompei, Ph.D., is founder and chief executive officer of Exergen. Exergen is a designer and manufacturer of medical and other devices. No other financial disclosures were reported.

In regions where more women undergo screening mammography, the detection of small cancers increases but mortality doesn’t change significantly, compared with regions where fewer women have the screening, according to a report published July 6 in JAMA Internal Medicine.

The finding indicates that screening mammography leads to “widespread overdiagnosis,” identifying many small, indolent, or regressive breast tumors that otherwise would not have become clinically apparent, reported Charles Harding, a data scientist and statistical analyst in Seattle, and his associates.

Ideally, screening mammography should result in increased detection of small (less advanced) cancers, decreased detection of large (more advanced) cancers, and reduced breast cancer–specific mortality. To examine whether this is what actually happens, Mr. Harding and his colleagues analyzed mammography rates among 16,120,349 women over age 40 residing in 547 counties across the country during a 1-year period, where the frequency of screening ranged from 39% to 78%.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

They correlated these findings with breast cancer incidence and mortality data in those regions for the ensuing 10 years. They identified 53,207 incident cases of breast cancer for their primary analysis.

There was a clear correlation between the number of users of screening mammography and breast cancer incidence. A 10% increase in screening was associated with a 16% mean increase in breast cancer incidence (relative risk, 1.16), or an absolute increase of 35-49 cases per 100,000. However, there was no significant change in breast cancer mortality (RR, 1.01).

When the data were stratified according to tumor size, the researchers found that the increase in breast cancer was confined to small tumors only (2 cm or less).

Moreover, “although it has been hoped that screening would allow breast-conserving surgical procedures to replace more extensive mastectomies, we saw no evidence supporting this change,” the investigators wrote (JAMA Intern. Med. 2015 July 6 [doi:10.1001/jamainternmed.2015.3043]).

Future research should focus on whether all women undergoing screening mammography have the same risk of overdiagnosis, or if overdiagnosis is more likely to occur in certain groups, Mr. Harding and his associates added.

Mr. Harding reported receiving funding from Exergen Corporation for this work. Another study author, Francesco Pompei, Ph.D., is founder and chief executive officer of Exergen. Exergen is a designer and manufacturer of medical and other devices. No other financial disclosures were reported.

In regions where more women undergo screening mammography, the detection of small cancers increases but mortality doesn’t change significantly, compared with regions where fewer women have the screening, according to a report published July 6 in JAMA Internal Medicine.

The finding indicates that screening mammography leads to “widespread overdiagnosis,” identifying many small, indolent, or regressive breast tumors that otherwise would not have become clinically apparent, reported Charles Harding, a data scientist and statistical analyst in Seattle, and his associates.

Ideally, screening mammography should result in increased detection of small (less advanced) cancers, decreased detection of large (more advanced) cancers, and reduced breast cancer–specific mortality. To examine whether this is what actually happens, Mr. Harding and his colleagues analyzed mammography rates among 16,120,349 women over age 40 residing in 547 counties across the country during a 1-year period, where the frequency of screening ranged from 39% to 78%.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

They correlated these findings with breast cancer incidence and mortality data in those regions for the ensuing 10 years. They identified 53,207 incident cases of breast cancer for their primary analysis.

There was a clear correlation between the number of users of screening mammography and breast cancer incidence. A 10% increase in screening was associated with a 16% mean increase in breast cancer incidence (relative risk, 1.16), or an absolute increase of 35-49 cases per 100,000. However, there was no significant change in breast cancer mortality (RR, 1.01).

When the data were stratified according to tumor size, the researchers found that the increase in breast cancer was confined to small tumors only (2 cm or less).

Moreover, “although it has been hoped that screening would allow breast-conserving surgical procedures to replace more extensive mastectomies, we saw no evidence supporting this change,” the investigators wrote (JAMA Intern. Med. 2015 July 6 [doi:10.1001/jamainternmed.2015.3043]).

Future research should focus on whether all women undergoing screening mammography have the same risk of overdiagnosis, or if overdiagnosis is more likely to occur in certain groups, Mr. Harding and his associates added.

Mr. Harding reported receiving funding from Exergen Corporation for this work. Another study author, Francesco Pompei, Ph.D., is founder and chief executive officer of Exergen. Exergen is a designer and manufacturer of medical and other devices. No other financial disclosures were reported.

Breast cancer is no longer the monolithic disease it once was. And now, depending on the type of breast cancer a patient has, appropriate treatment is getting easier. According to the Annual Report to the Nation on the Status of Cancer, 1975-2011, released by the National Cancer Institute (NCI) in Bethesda, Maryland, there are data on the national incidence of the 4 major molecular subtypes of breast cancer by age, race and ethnicity, socioeconomic level, and other factors for the first time.

Related: Advances in Targeted Therapy for Breast Cancer

Although the subtypes—which relate to the hormone receptor (HR) status and expression of the HER₂ gene—were already known prior to the report, incidence was not. But beginning in 2010, cancer registries have been required to report both HR and HER₂ status for breast cancer cases. Being able to divide the data in previously unavailable ways will help researchers more accurately stratify breast cancer by risk, NCI says.

The least aggressive breast cancer subtype, HR+/HER₂- was the most prevalent, at 73% of all breast cancer cases. Rates were highest among non-Hispanic whites living in low-poverty areas.

Related: Timely Assessment of Cancer Symptoms

“Triple-negative” breast cancer, HR-/HER₂-, made up 13% of all cases and had the worst prognosis. Non-Hispanic blacks had the highest rates of triple-negative breast cancer, as well as the highest rates of late-stage disease and poorly/undifferentiated pathology.

The HR+/HER₂+ breast cancer, which accounted for 10% of all cases, was more common in Idaho, Tennessee, and Pennsylvania. No states were statistically different from the national rates for HR-/HER₂+, which accounted for 5% of all cases. Triple-negative rates were lower in the northwestern U.S. and higher in the southeastern U.S.

Related: Can Endocrine Therapy Adherence Be Improved?

The data can also be used to help women better understand health implications based on their breast cancer subtype. In one study cited by NCI, slightly more than half of the women reported their correct estrogen status, HER₂ status, and stage of cancer. Only about 1 in 5 reported the correct grade. However, women who understood the basis for their treatment, the researchers found, were generally more satisfied with treatment.

Sources
National Cancer Institute. New analysis of breast cancer subtypes could lead to better risk stratification; Annual Report to the Nation shows that mortality and incidence for most cancers continue to decline [press release]. Bethesda, MD: National Cancer Institute; March 30, 2015.

National Cancer Institute. Annual Report to the Nation on the Status of Cancer, 1975-2011. Bethesda, MD: National Cancer Institute; 2015.

National Cancer Institute. Annual Report to the Nation on the Status of Cancer, 1975 -2011: questions and answers [press release]. Bethesda, MD: National Cancer Institute; March 30, 2015.

Breast cancer is no longer the monolithic disease it once was. And now, depending on the type of breast cancer a patient has, appropriate treatment is getting easier. According to the Annual Report to the Nation on the Status of Cancer, 1975-2011, released by the National Cancer Institute (NCI) in Bethesda, Maryland, there are data on the national incidence of the 4 major molecular subtypes of breast cancer by age, race and ethnicity, socioeconomic level, and other factors for the first time.

Related: Advances in Targeted Therapy for Breast Cancer

Although the subtypes—which relate to the hormone receptor (HR) status and expression of the HER₂ gene—were already known prior to the report, incidence was not. But beginning in 2010, cancer registries have been required to report both HR and HER₂ status for breast cancer cases. Being able to divide the data in previously unavailable ways will help researchers more accurately stratify breast cancer by risk, NCI says.

The least aggressive breast cancer subtype, HR+/HER₂- was the most prevalent, at 73% of all breast cancer cases. Rates were highest among non-Hispanic whites living in low-poverty areas.

Related: Timely Assessment of Cancer Symptoms

“Triple-negative” breast cancer, HR-/HER₂-, made up 13% of all cases and had the worst prognosis. Non-Hispanic blacks had the highest rates of triple-negative breast cancer, as well as the highest rates of late-stage disease and poorly/undifferentiated pathology.

The HR+/HER₂+ breast cancer, which accounted for 10% of all cases, was more common in Idaho, Tennessee, and Pennsylvania. No states were statistically different from the national rates for HR-/HER₂+, which accounted for 5% of all cases. Triple-negative rates were lower in the northwestern U.S. and higher in the southeastern U.S.

Related: Can Endocrine Therapy Adherence Be Improved?

The data can also be used to help women better understand health implications based on their breast cancer subtype. In one study cited by NCI, slightly more than half of the women reported their correct estrogen status, HER₂ status, and stage of cancer. Only about 1 in 5 reported the correct grade. However, women who understood the basis for their treatment, the researchers found, were generally more satisfied with treatment.

Sources
National Cancer Institute. New analysis of breast cancer subtypes could lead to better risk stratification; Annual Report to the Nation shows that mortality and incidence for most cancers continue to decline [press release]. Bethesda, MD: National Cancer Institute; March 30, 2015.

National Cancer Institute. Annual Report to the Nation on the Status of Cancer, 1975-2011. Bethesda, MD: National Cancer Institute; 2015.

National Cancer Institute. Annual Report to the Nation on the Status of Cancer, 1975 -2011: questions and answers [press release]. Bethesda, MD: National Cancer Institute; March 30, 2015.

Breast cancer is no longer the monolithic disease it once was. And now, depending on the type of breast cancer a patient has, appropriate treatment is getting easier. According to the Annual Report to the Nation on the Status of Cancer, 1975-2011, released by the National Cancer Institute (NCI) in Bethesda, Maryland, there are data on the national incidence of the 4 major molecular subtypes of breast cancer by age, race and ethnicity, socioeconomic level, and other factors for the first time.

Related: Advances in Targeted Therapy for Breast Cancer

Although the subtypes—which relate to the hormone receptor (HR) status and expression of the HER₂ gene—were already known prior to the report, incidence was not. But beginning in 2010, cancer registries have been required to report both HR and HER₂ status for breast cancer cases. Being able to divide the data in previously unavailable ways will help researchers more accurately stratify breast cancer by risk, NCI says.

The least aggressive breast cancer subtype, HR+/HER₂- was the most prevalent, at 73% of all breast cancer cases. Rates were highest among non-Hispanic whites living in low-poverty areas.

Related: Timely Assessment of Cancer Symptoms

“Triple-negative” breast cancer, HR-/HER₂-, made up 13% of all cases and had the worst prognosis. Non-Hispanic blacks had the highest rates of triple-negative breast cancer, as well as the highest rates of late-stage disease and poorly/undifferentiated pathology.

The HR+/HER₂+ breast cancer, which accounted for 10% of all cases, was more common in Idaho, Tennessee, and Pennsylvania. No states were statistically different from the national rates for HR-/HER₂+, which accounted for 5% of all cases. Triple-negative rates were lower in the northwestern U.S. and higher in the southeastern U.S.

Related: Can Endocrine Therapy Adherence Be Improved?

The data can also be used to help women better understand health implications based on their breast cancer subtype. In one study cited by NCI, slightly more than half of the women reported their correct estrogen status, HER₂ status, and stage of cancer. Only about 1 in 5 reported the correct grade. However, women who understood the basis for their treatment, the researchers found, were generally more satisfied with treatment.

Sources
National Cancer Institute. New analysis of breast cancer subtypes could lead to better risk stratification; Annual Report to the Nation shows that mortality and incidence for most cancers continue to decline [press release]. Bethesda, MD: National Cancer Institute; March 30, 2015.

National Cancer Institute. Annual Report to the Nation on the Status of Cancer, 1975-2011. Bethesda, MD: National Cancer Institute; 2015.

National Cancer Institute. Annual Report to the Nation on the Status of Cancer, 1975 -2011: questions and answers [press release]. Bethesda, MD: National Cancer Institute; March 30, 2015.

The number of states that require notification to a woman who is identified on mammography as having heterogeneous (Breast Imaging-Reporting and Data System [BI-RADS] C) or extremely dense breasts (BI-RADS D) is growing. In fact, Michigan became the 22nd state to require such notification when its law went into effect on June 1, 2015. How do we advise our patients who come to us wondering what they should do with the new-found information?

Since supplemental imaging after normal mammography findings can result in false positives and potentially unnecessary biopsies or treatment, Kerlikowski and colleagues investigated for which patients supplemental screening could be beneficial. In other words, which patients are at highest risk for interval cancer (invasive cancer diagnosed within 12 months of a normal mammogram), as these women would be most likely to benefit from supplemental imaging that could potentially detect a tumor not identified on digital screening mammography.

Details of the study
The researchers included 831,455 digital screening mammography examinations performed among 365,426 women aged 40 to 74 years who did not have a history of breast cancer or breast implants and had complete information on demographic and breast health history. To calculate breast cancer risk, they used the Breast Cancer Surveillance Consortium (BCSC) 5-year risk model, which requires 5 risk factors: first-degree relatives with history of breast cancer, history of breast biopsy, BI-RADS breast density, and race/ethnicity. They used breast density to stratify women by risk for interval cancer within the next year and to identify women at increased 5-year risk for breast cancer.

In which patient populations are cases of interval cancer highest?
The authors found the interval cancer rates to exceed 1 case per 1,000 mammography examinations among:

The authors point out that, together, these 2 latter groups represent 24% of women aged 40 to 74 years with dense breasts, or 12% of women having screening mammography.

For women aged 40 to 49 years, interval cancer rates were less than 1 case per 1,000 examinations for all density categories. For 51% of these women with heterogeneously dense breasts, the 5-year risk of breast cancer was low to average (0% to 1.66%), with interval cancer rates of 0.58 to 0.63 per 1,000 examinations. For 52.5% of 40- to 49-year-old women with extremely dense breasts, the 5-year risk of breast cancer was low to average, with interval cancer rates of 0.72 to 0.89 cases per 1,000 examinations.

The interval cancer rate for women with scattered fibroglandular densities (BI-RADS B) and 5-year risk of 2.50% or greater was 0.90 cases per 1,000 mammography examinations.

Kerlikowski and colleagues conclude that breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. 

What this evidence means for practice
BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient–provider discussions about alternative screening strategies, as the study authors state. However, there remains a huge gap in our knowledge about whether supplemental imaging in any of these risk groups improved stage of diagnosis or breast cancer–specific mortality.

Nearly all national guidelines groups (US Preventive Services Task Force,¹ American College of Obstetricians and Gynecologists,² National Comprehensive Cancer Network,³ and the American Cancer Society⁴) concur that supplemental breast imaging should not be performed on women with dense breasts until there are reasonable data that demonstrate an improvement in stage of diagnosis or breast cancer mortality.
—Mark D. Pearlman, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The number of states that require notification to a woman who is identified on mammography as having heterogeneous (Breast Imaging-Reporting and Data System [BI-RADS] C) or extremely dense breasts (BI-RADS D) is growing. In fact, Michigan became the 22nd state to require such notification when its law went into effect on June 1, 2015. How do we advise our patients who come to us wondering what they should do with the new-found information?

Since supplemental imaging after normal mammography findings can result in false positives and potentially unnecessary biopsies or treatment, Kerlikowski and colleagues investigated for which patients supplemental screening could be beneficial. In other words, which patients are at highest risk for interval cancer (invasive cancer diagnosed within 12 months of a normal mammogram), as these women would be most likely to benefit from supplemental imaging that could potentially detect a tumor not identified on digital screening mammography.

Details of the study
The researchers included 831,455 digital screening mammography examinations performed among 365,426 women aged 40 to 74 years who did not have a history of breast cancer or breast implants and had complete information on demographic and breast health history. To calculate breast cancer risk, they used the Breast Cancer Surveillance Consortium (BCSC) 5-year risk model, which requires 5 risk factors: first-degree relatives with history of breast cancer, history of breast biopsy, BI-RADS breast density, and race/ethnicity. They used breast density to stratify women by risk for interval cancer within the next year and to identify women at increased 5-year risk for breast cancer.

In which patient populations are cases of interval cancer highest?
The authors found the interval cancer rates to exceed 1 case per 1,000 mammography examinations among:

The authors point out that, together, these 2 latter groups represent 24% of women aged 40 to 74 years with dense breasts, or 12% of women having screening mammography.

For women aged 40 to 49 years, interval cancer rates were less than 1 case per 1,000 examinations for all density categories. For 51% of these women with heterogeneously dense breasts, the 5-year risk of breast cancer was low to average (0% to 1.66%), with interval cancer rates of 0.58 to 0.63 per 1,000 examinations. For 52.5% of 40- to 49-year-old women with extremely dense breasts, the 5-year risk of breast cancer was low to average, with interval cancer rates of 0.72 to 0.89 cases per 1,000 examinations.

The interval cancer rate for women with scattered fibroglandular densities (BI-RADS B) and 5-year risk of 2.50% or greater was 0.90 cases per 1,000 mammography examinations.

Kerlikowski and colleagues conclude that breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. 

What this evidence means for practice
BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient–provider discussions about alternative screening strategies, as the study authors state. However, there remains a huge gap in our knowledge about whether supplemental imaging in any of these risk groups improved stage of diagnosis or breast cancer–specific mortality.

Nearly all national guidelines groups (US Preventive Services Task Force,¹ American College of Obstetricians and Gynecologists,² National Comprehensive Cancer Network,³ and the American Cancer Society⁴) concur that supplemental breast imaging should not be performed on women with dense breasts until there are reasonable data that demonstrate an improvement in stage of diagnosis or breast cancer mortality.
—Mark D. Pearlman, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The number of states that require notification to a woman who is identified on mammography as having heterogeneous (Breast Imaging-Reporting and Data System [BI-RADS] C) or extremely dense breasts (BI-RADS D) is growing. In fact, Michigan became the 22nd state to require such notification when its law went into effect on June 1, 2015. How do we advise our patients who come to us wondering what they should do with the new-found information?

Since supplemental imaging after normal mammography findings can result in false positives and potentially unnecessary biopsies or treatment, Kerlikowski and colleagues investigated for which patients supplemental screening could be beneficial. In other words, which patients are at highest risk for interval cancer (invasive cancer diagnosed within 12 months of a normal mammogram), as these women would be most likely to benefit from supplemental imaging that could potentially detect a tumor not identified on digital screening mammography.

Details of the study
The researchers included 831,455 digital screening mammography examinations performed among 365,426 women aged 40 to 74 years who did not have a history of breast cancer or breast implants and had complete information on demographic and breast health history. To calculate breast cancer risk, they used the Breast Cancer Surveillance Consortium (BCSC) 5-year risk model, which requires 5 risk factors: first-degree relatives with history of breast cancer, history of breast biopsy, BI-RADS breast density, and race/ethnicity. They used breast density to stratify women by risk for interval cancer within the next year and to identify women at increased 5-year risk for breast cancer.

In which patient populations are cases of interval cancer highest?
The authors found the interval cancer rates to exceed 1 case per 1,000 mammography examinations among:

The authors point out that, together, these 2 latter groups represent 24% of women aged 40 to 74 years with dense breasts, or 12% of women having screening mammography.

For women aged 40 to 49 years, interval cancer rates were less than 1 case per 1,000 examinations for all density categories. For 51% of these women with heterogeneously dense breasts, the 5-year risk of breast cancer was low to average (0% to 1.66%), with interval cancer rates of 0.58 to 0.63 per 1,000 examinations. For 52.5% of 40- to 49-year-old women with extremely dense breasts, the 5-year risk of breast cancer was low to average, with interval cancer rates of 0.72 to 0.89 cases per 1,000 examinations.

The interval cancer rate for women with scattered fibroglandular densities (BI-RADS B) and 5-year risk of 2.50% or greater was 0.90 cases per 1,000 mammography examinations.

Kerlikowski and colleagues conclude that breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. 

What this evidence means for practice
BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient–provider discussions about alternative screening strategies, as the study authors state. However, there remains a huge gap in our knowledge about whether supplemental imaging in any of these risk groups improved stage of diagnosis or breast cancer–specific mortality.

Nearly all national guidelines groups (US Preventive Services Task Force,¹ American College of Obstetricians and Gynecologists,² National Comprehensive Cancer Network,³ and the American Cancer Society⁴) concur that supplemental breast imaging should not be performed on women with dense breasts until there are reasonable data that demonstrate an improvement in stage of diagnosis or breast cancer mortality.
—Mark D. Pearlman, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Urea cream is more effective at preventing hand-foot syndrome (HFS) than is a medical ointment high in antioxidants for patients receiving capecitabine, according to a randomized phase III study published online in the Journal of Clinical Oncology.

During a 6-week treatment period, 17 of 76 patients (22.4%) who used 10% urea cream experienced HFS, compared with 30 of 76 patients (39.5%) who used the new ointment Mapisal, which has been available on the German market since 2011 (odds ratio 2.37; 95% CI 1.14 to 4.84; P = .02). The distribution of HFS grades within the groups was similar, with the majority having grade 1 and about 6% experiencing grade 3 HFS. A secondary endpoint, time to develop HFS, was significantly longer in the urea cream group (J. Clin. Oncol. 2015 June 29 [doi:10.1200/JCO.2014.60.4587]).

The result was unexpected. Mapisal contains several antioxidants and oil extracts and exhibits a high radical protection factor, which was hypothesized to be of benefit due to a decline in antioxidative capacity of the skin in patients using capecitabine. “The most striking explanation for the observed ineffectiveness of Mapisal is that either the hypothesis – that is, that Mapisal’s crucial mode of action against HFS is to act as an antioxidant against free radicals – is incorrect, or that this is not the main mechanism of HFS development, at least in the case of capecitabine,” wrote Dr. Ralf-Dieter Hofheinz of University Hospital Mannheim, Germany, and colleagues.

Between 2012 and 2013, the study enrolled 160 patients with GI tumors or breast cancer who were being treated with capecitabine, and 152 were randomly assigned to receive prophylactic treatment with either Mapisal or 10% urea cream for a 6-week period. Aside from HFS, adverse events were similar between the groups. After the treatment period, skin-related quality of life was significantly lower in the Mapisal vs. urea group.

The results of this study, along with findings from a previous phase II study demonstrating activity of urea cream in patients treated with sorafenib, supports the idea that urea cream is an appropriate prophylaxis for HFS and a reasonable standard for future investigations, the researchers noted.

Urea cream is more effective at preventing hand-foot syndrome (HFS) than is a medical ointment high in antioxidants for patients receiving capecitabine, according to a randomized phase III study published online in the Journal of Clinical Oncology.

During a 6-week treatment period, 17 of 76 patients (22.4%) who used 10% urea cream experienced HFS, compared with 30 of 76 patients (39.5%) who used the new ointment Mapisal, which has been available on the German market since 2011 (odds ratio 2.37; 95% CI 1.14 to 4.84; P = .02). The distribution of HFS grades within the groups was similar, with the majority having grade 1 and about 6% experiencing grade 3 HFS. A secondary endpoint, time to develop HFS, was significantly longer in the urea cream group (J. Clin. Oncol. 2015 June 29 [doi:10.1200/JCO.2014.60.4587]).

The result was unexpected. Mapisal contains several antioxidants and oil extracts and exhibits a high radical protection factor, which was hypothesized to be of benefit due to a decline in antioxidative capacity of the skin in patients using capecitabine. “The most striking explanation for the observed ineffectiveness of Mapisal is that either the hypothesis – that is, that Mapisal’s crucial mode of action against HFS is to act as an antioxidant against free radicals – is incorrect, or that this is not the main mechanism of HFS development, at least in the case of capecitabine,” wrote Dr. Ralf-Dieter Hofheinz of University Hospital Mannheim, Germany, and colleagues.

Between 2012 and 2013, the study enrolled 160 patients with GI tumors or breast cancer who were being treated with capecitabine, and 152 were randomly assigned to receive prophylactic treatment with either Mapisal or 10% urea cream for a 6-week period. Aside from HFS, adverse events were similar between the groups. After the treatment period, skin-related quality of life was significantly lower in the Mapisal vs. urea group.

The results of this study, along with findings from a previous phase II study demonstrating activity of urea cream in patients treated with sorafenib, supports the idea that urea cream is an appropriate prophylaxis for HFS and a reasonable standard for future investigations, the researchers noted.

Urea cream is more effective at preventing hand-foot syndrome (HFS) than is a medical ointment high in antioxidants for patients receiving capecitabine, according to a randomized phase III study published online in the Journal of Clinical Oncology.

During a 6-week treatment period, 17 of 76 patients (22.4%) who used 10% urea cream experienced HFS, compared with 30 of 76 patients (39.5%) who used the new ointment Mapisal, which has been available on the German market since 2011 (odds ratio 2.37; 95% CI 1.14 to 4.84; P = .02). The distribution of HFS grades within the groups was similar, with the majority having grade 1 and about 6% experiencing grade 3 HFS. A secondary endpoint, time to develop HFS, was significantly longer in the urea cream group (J. Clin. Oncol. 2015 June 29 [doi:10.1200/JCO.2014.60.4587]).

The result was unexpected. Mapisal contains several antioxidants and oil extracts and exhibits a high radical protection factor, which was hypothesized to be of benefit due to a decline in antioxidative capacity of the skin in patients using capecitabine. “The most striking explanation for the observed ineffectiveness of Mapisal is that either the hypothesis – that is, that Mapisal’s crucial mode of action against HFS is to act as an antioxidant against free radicals – is incorrect, or that this is not the main mechanism of HFS development, at least in the case of capecitabine,” wrote Dr. Ralf-Dieter Hofheinz of University Hospital Mannheim, Germany, and colleagues.

Between 2012 and 2013, the study enrolled 160 patients with GI tumors or breast cancer who were being treated with capecitabine, and 152 were randomly assigned to receive prophylactic treatment with either Mapisal or 10% urea cream for a 6-week period. Aside from HFS, adverse events were similar between the groups. After the treatment period, skin-related quality of life was significantly lower in the Mapisal vs. urea group.

The results of this study, along with findings from a previous phase II study demonstrating activity of urea cream in patients treated with sorafenib, supports the idea that urea cream is an appropriate prophylaxis for HFS and a reasonable standard for future investigations, the researchers noted.

Although bilateral salpingo-oophorectomy is known to prevent breast and ovarian cancer in BRCA mutation carriers,¹ published reports also have suggested that, among mutation carriers with breast cancer, oophorectomy improves survival. In this retrospective analysis, investigators focused on women with stage I or II breast cancer and a BRCA1 or BRCA2 mutation, observing them for as long as 20 years after diagnosis. Survival rates were compared between women who did and did not undergo oophorectomy.

Details of the trial
Metcalfe and colleagues followed women with a BRCA1 or BRCA2 mutation and intact ovaries who were diagnosed with breast cancer at age 65 or younger between 1975 and 2008, tracking them for a mean of 12.5 years. Of 676 women, 345 underwent oophorectomy, usually with the intent of preventing ovarian cancer.

Overall, oophorectomy was associated with a 56% reduction in the risk of breast cancer-specific mortality (P = .005). Among breast cancer survivors with a BRCA1 mutation, oophorectomy was associated with a significant 62% reduction in breast cancer mortality. Among BRCA2 carriers, the observed 43% reduction in breast cancer mortality did not achieve statistical significance (P = .23).

Full impact of oophorectomy may be difficult to tease out
As Metcalfe and colleagues point out, recent improvements in breast imaging that have led to earlier diagnosis, as well as improvements in the treatment of breast cancer, might attenuate the mortality benefits observed with oophorectomy.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
This important report underscores the importance of testing all women with early-stage breast cancer for BRCA mutations, and informs the management of known BRCA1 carriers with breast cancer.
—Andrew M. Kaunitz, MD

Although bilateral salpingo-oophorectomy is known to prevent breast and ovarian cancer in BRCA mutation carriers,¹ published reports also have suggested that, among mutation carriers with breast cancer, oophorectomy improves survival. In this retrospective analysis, investigators focused on women with stage I or II breast cancer and a BRCA1 or BRCA2 mutation, observing them for as long as 20 years after diagnosis. Survival rates were compared between women who did and did not undergo oophorectomy.

Details of the trial
Metcalfe and colleagues followed women with a BRCA1 or BRCA2 mutation and intact ovaries who were diagnosed with breast cancer at age 65 or younger between 1975 and 2008, tracking them for a mean of 12.5 years. Of 676 women, 345 underwent oophorectomy, usually with the intent of preventing ovarian cancer.

Overall, oophorectomy was associated with a 56% reduction in the risk of breast cancer-specific mortality (P = .005). Among breast cancer survivors with a BRCA1 mutation, oophorectomy was associated with a significant 62% reduction in breast cancer mortality. Among BRCA2 carriers, the observed 43% reduction in breast cancer mortality did not achieve statistical significance (P = .23).

Full impact of oophorectomy may be difficult to tease out
As Metcalfe and colleagues point out, recent improvements in breast imaging that have led to earlier diagnosis, as well as improvements in the treatment of breast cancer, might attenuate the mortality benefits observed with oophorectomy.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
This important report underscores the importance of testing all women with early-stage breast cancer for BRCA mutations, and informs the management of known BRCA1 carriers with breast cancer.
—Andrew M. Kaunitz, MD

Although bilateral salpingo-oophorectomy is known to prevent breast and ovarian cancer in BRCA mutation carriers,¹ published reports also have suggested that, among mutation carriers with breast cancer, oophorectomy improves survival. In this retrospective analysis, investigators focused on women with stage I or II breast cancer and a BRCA1 or BRCA2 mutation, observing them for as long as 20 years after diagnosis. Survival rates were compared between women who did and did not undergo oophorectomy.

Details of the trial
Metcalfe and colleagues followed women with a BRCA1 or BRCA2 mutation and intact ovaries who were diagnosed with breast cancer at age 65 or younger between 1975 and 2008, tracking them for a mean of 12.5 years. Of 676 women, 345 underwent oophorectomy, usually with the intent of preventing ovarian cancer.

Overall, oophorectomy was associated with a 56% reduction in the risk of breast cancer-specific mortality (P = .005). Among breast cancer survivors with a BRCA1 mutation, oophorectomy was associated with a significant 62% reduction in breast cancer mortality. Among BRCA2 carriers, the observed 43% reduction in breast cancer mortality did not achieve statistical significance (P = .23).

Full impact of oophorectomy may be difficult to tease out
As Metcalfe and colleagues point out, recent improvements in breast imaging that have led to earlier diagnosis, as well as improvements in the treatment of breast cancer, might attenuate the mortality benefits observed with oophorectomy.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
This important report underscores the importance of testing all women with early-stage breast cancer for BRCA mutations, and informs the management of known BRCA1 carriers with breast cancer.
—Andrew M. Kaunitz, MD