Breast Cancer

Patients with residual disease after neoadjuvant chemotherapy and surgery for breast cancer had a 60%-280% increased risk for locoregional recurrence, compared with patients with a pathologic complete response, an analysis of data from 12 large clinical trials found.

Investigators analyzed data on 11,955 patients with stage I-III breast cancer who underwent neoadjuvant chemotherapy in studies with long-term follow-up and information on complete pathologic response (no residual cancer in the breast and no cancer in the axillary lymph nodes after surgery). They included 5,252 patients in a multivariate analysis of predictors of locoregional recurrence a median of 5 years after treatment.

Overall, the likelihood of locoregional recurrence was low – less than 10%. Locoregional recurrence was seen in 5.5% of patients with a complete pathologic response to neoadjuvant chemotherapy and in 7.1% of patients without a complete response, a significant 60% increase in risk without a complete response, Dr. Eleftherios Mamounas reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology.

Patients with residual cancer in the breast after surgery had a 60% higher risk for locoregional recurrence, and patients with residual cancer in the axillary lymph nodes had a 280% increased risk for locoregional recurrence, compared with patients who had a complete pathologic response, reported Dr. Mamounas, professor of surgery at the University of Central Florida, and medical director of the comprehensive breast program at the University of Florida Health Cancer Center, both in Orlando.

Breast cancer subtypes remained independent predictors of locoregional recurrence, regardless of whether patients had a pathologic complete response or not. The cancer recurred locally or regionally in 4% of patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2–) grade 1 or 2 cancer, 9% of patients with HR+/HER2– grade 3 cancer, 15% of patients with HR–/HER2+ cancer, 10% of patients with HR+/HER2+ cancer, and 12% of patients with HR–/HER2– cancer (also known as hormone receptor–negative or triple-negative breast cancer).

Those rates would be different today because of more effective treatments for HER2+ breast cancer, he noted.

"For all breast cancer subtypes except for HR+/HER2– grade 1 and 2, there was a progressive increase in the locoregional recurrence rates with decreasing rates of pathologic complete response," he said. In other words, recurrence rates went from highest to lowest in patients "having positive nodes, versus having residual disease in the breast with negative nodes, versus having complete pathologic response," he explained.

Among patients with triple-negative cancer, for example, locoregional recurrence rates went from 6.2% in those with a complete response to 11.9% in patients with residual cancer in the breast but not lymph nodes and 22.1% in those who had positive nodes after treatment.

A pathologic complete response predicted lower locoregional recurrence rates with the various cancer subtypes, regardless of whether the patient underwent lumpectomy or mastectomy, he said.

Based on these results and previously published studies, "we have a lot of evidence that pathologic complete response is predictive of outcome, both in terms of systemic recurrence and also in terms of local recurrence," Dr. Mamounas commented. A previous meta-analysis that reported conflicting results for systemic recurrence "did not quite confirm that an incremental increase in pathologic complete response will improve overall survival, but there are a lot of technical issues if you look at the different studies that were included in the meta-analysis. The bar was very high to prove that concept."

Recurrence is less likely after a pathologic complete response in patients with HER2+ breast cancer, triple-negative cancer, or highly proliferative estrogen receptor–positive breast cancer, he said. That may not be the case for patients with estrogen receptor–positive, HER2– grade 1 disease, who do very well regardless, he added.

"Our findings have clinical implications relative to further tailoring the use of adjuvant radiation therapy after neoadjuvant chemotherapy and support the conduct of ongoing clinical trials attempting to tailor locoregional therapy in this setting," Dr. Mamounas said.

Dr. Mamounas reported financial associations with Genomic Health, GE Healthcare, Celgene, Pfizer, Eisai, and Genentech/Roche. Some of his coinvestigators reported associations with multiple companies.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Patients with residual disease after neoadjuvant chemotherapy and surgery for breast cancer had a 60%-280% increased risk for locoregional recurrence, compared with patients with a pathologic complete response, an analysis of data from 12 large clinical trials found.

Investigators analyzed data on 11,955 patients with stage I-III breast cancer who underwent neoadjuvant chemotherapy in studies with long-term follow-up and information on complete pathologic response (no residual cancer in the breast and no cancer in the axillary lymph nodes after surgery). They included 5,252 patients in a multivariate analysis of predictors of locoregional recurrence a median of 5 years after treatment.

Overall, the likelihood of locoregional recurrence was low – less than 10%. Locoregional recurrence was seen in 5.5% of patients with a complete pathologic response to neoadjuvant chemotherapy and in 7.1% of patients without a complete response, a significant 60% increase in risk without a complete response, Dr. Eleftherios Mamounas reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology.

Patients with residual cancer in the breast after surgery had a 60% higher risk for locoregional recurrence, and patients with residual cancer in the axillary lymph nodes had a 280% increased risk for locoregional recurrence, compared with patients who had a complete pathologic response, reported Dr. Mamounas, professor of surgery at the University of Central Florida, and medical director of the comprehensive breast program at the University of Florida Health Cancer Center, both in Orlando.

Breast cancer subtypes remained independent predictors of locoregional recurrence, regardless of whether patients had a pathologic complete response or not. The cancer recurred locally or regionally in 4% of patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2–) grade 1 or 2 cancer, 9% of patients with HR+/HER2– grade 3 cancer, 15% of patients with HR–/HER2+ cancer, 10% of patients with HR+/HER2+ cancer, and 12% of patients with HR–/HER2– cancer (also known as hormone receptor–negative or triple-negative breast cancer).

Those rates would be different today because of more effective treatments for HER2+ breast cancer, he noted.

"For all breast cancer subtypes except for HR+/HER2– grade 1 and 2, there was a progressive increase in the locoregional recurrence rates with decreasing rates of pathologic complete response," he said. In other words, recurrence rates went from highest to lowest in patients "having positive nodes, versus having residual disease in the breast with negative nodes, versus having complete pathologic response," he explained.

Among patients with triple-negative cancer, for example, locoregional recurrence rates went from 6.2% in those with a complete response to 11.9% in patients with residual cancer in the breast but not lymph nodes and 22.1% in those who had positive nodes after treatment.

A pathologic complete response predicted lower locoregional recurrence rates with the various cancer subtypes, regardless of whether the patient underwent lumpectomy or mastectomy, he said.

Based on these results and previously published studies, "we have a lot of evidence that pathologic complete response is predictive of outcome, both in terms of systemic recurrence and also in terms of local recurrence," Dr. Mamounas commented. A previous meta-analysis that reported conflicting results for systemic recurrence "did not quite confirm that an incremental increase in pathologic complete response will improve overall survival, but there are a lot of technical issues if you look at the different studies that were included in the meta-analysis. The bar was very high to prove that concept."

Recurrence is less likely after a pathologic complete response in patients with HER2+ breast cancer, triple-negative cancer, or highly proliferative estrogen receptor–positive breast cancer, he said. That may not be the case for patients with estrogen receptor–positive, HER2– grade 1 disease, who do very well regardless, he added.

"Our findings have clinical implications relative to further tailoring the use of adjuvant radiation therapy after neoadjuvant chemotherapy and support the conduct of ongoing clinical trials attempting to tailor locoregional therapy in this setting," Dr. Mamounas said.

Dr. Mamounas reported financial associations with Genomic Health, GE Healthcare, Celgene, Pfizer, Eisai, and Genentech/Roche. Some of his coinvestigators reported associations with multiple companies.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Patients with residual disease after neoadjuvant chemotherapy and surgery for breast cancer had a 60%-280% increased risk for locoregional recurrence, compared with patients with a pathologic complete response, an analysis of data from 12 large clinical trials found.

Investigators analyzed data on 11,955 patients with stage I-III breast cancer who underwent neoadjuvant chemotherapy in studies with long-term follow-up and information on complete pathologic response (no residual cancer in the breast and no cancer in the axillary lymph nodes after surgery). They included 5,252 patients in a multivariate analysis of predictors of locoregional recurrence a median of 5 years after treatment.

Overall, the likelihood of locoregional recurrence was low – less than 10%. Locoregional recurrence was seen in 5.5% of patients with a complete pathologic response to neoadjuvant chemotherapy and in 7.1% of patients without a complete response, a significant 60% increase in risk without a complete response, Dr. Eleftherios Mamounas reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology.

Patients with residual cancer in the breast after surgery had a 60% higher risk for locoregional recurrence, and patients with residual cancer in the axillary lymph nodes had a 280% increased risk for locoregional recurrence, compared with patients who had a complete pathologic response, reported Dr. Mamounas, professor of surgery at the University of Central Florida, and medical director of the comprehensive breast program at the University of Florida Health Cancer Center, both in Orlando.

Breast cancer subtypes remained independent predictors of locoregional recurrence, regardless of whether patients had a pathologic complete response or not. The cancer recurred locally or regionally in 4% of patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2–) grade 1 or 2 cancer, 9% of patients with HR+/HER2– grade 3 cancer, 15% of patients with HR–/HER2+ cancer, 10% of patients with HR+/HER2+ cancer, and 12% of patients with HR–/HER2– cancer (also known as hormone receptor–negative or triple-negative breast cancer).

Those rates would be different today because of more effective treatments for HER2+ breast cancer, he noted.

"For all breast cancer subtypes except for HR+/HER2– grade 1 and 2, there was a progressive increase in the locoregional recurrence rates with decreasing rates of pathologic complete response," he said. In other words, recurrence rates went from highest to lowest in patients "having positive nodes, versus having residual disease in the breast with negative nodes, versus having complete pathologic response," he explained.

Among patients with triple-negative cancer, for example, locoregional recurrence rates went from 6.2% in those with a complete response to 11.9% in patients with residual cancer in the breast but not lymph nodes and 22.1% in those who had positive nodes after treatment.

A pathologic complete response predicted lower locoregional recurrence rates with the various cancer subtypes, regardless of whether the patient underwent lumpectomy or mastectomy, he said.

Based on these results and previously published studies, "we have a lot of evidence that pathologic complete response is predictive of outcome, both in terms of systemic recurrence and also in terms of local recurrence," Dr. Mamounas commented. A previous meta-analysis that reported conflicting results for systemic recurrence "did not quite confirm that an incremental increase in pathologic complete response will improve overall survival, but there are a lot of technical issues if you look at the different studies that were included in the meta-analysis. The bar was very high to prove that concept."

Recurrence is less likely after a pathologic complete response in patients with HER2+ breast cancer, triple-negative cancer, or highly proliferative estrogen receptor–positive breast cancer, he said. That may not be the case for patients with estrogen receptor–positive, HER2– grade 1 disease, who do very well regardless, he added.

"Our findings have clinical implications relative to further tailoring the use of adjuvant radiation therapy after neoadjuvant chemotherapy and support the conduct of ongoing clinical trials attempting to tailor locoregional therapy in this setting," Dr. Mamounas said.

Dr. Mamounas reported financial associations with Genomic Health, GE Healthcare, Celgene, Pfizer, Eisai, and Genentech/Roche. Some of his coinvestigators reported associations with multiple companies.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

The use of bilateral mastectomy has increased significantly in California, but the results from an observational cohort study show it achieves similar mortality reductions to breast-conserving surgery plus radiation, while unilateral mastectomy is associated with higher mortality.

In an analysis of data from nearly 190,000 patients in the population-based California Cancer Registry, no significant differences were found in all-cause mortality between patients who underwent bilateral mastectomy and those who had breast-conserving surgery with radiation (HR, 1.02 [95%CI, 0.94-1.11]); however, unilateral mastectomy was linked to 35% higher all-cause mortality than was breast-conserving surgery with radiation (HR, 1.35 [95% CI, 1.32-1.39]).

Dr. Allison W. Kurian of Stanford (Calif.)University and colleagues also found the rate of bilateral mastectomy had increased 14.3% each year, from 2% of all patients in 1998 to 12.3% in 2011, with it more commonly used among non-Hispanic white women, those with private insurance, and those who received care at a National Cancer Institute–designated cancer center, according to a paper published Sept. 2 in JAMA [doi:10.1001/jama.2014.10707].

"In a time of increasing concern over treatment, the risk-benefit ratio of bilateral mastectomy warrants careful consideration and raises the larger question of how physicians and society should respond to a patient’s preference for a morbid, costly intervention of dubious effectiveness," the authors wrote.

In an accompanying editorial, Dr. Lisa A. Newman of the comprehensive cancer center, University of Michigan, Ann Arbor, said the findings refute patient assumptions that bilateral mastectomy represents their best chance for a cure, and for eliminating the perceived cancer threat to the unaffected breast, and advocated a more calm and considered approach to treatment decision making (JAMA 2014 Sept. 2 [doi:10.1001/jama.2014.11308]).

"Physicians should not permit excessive treatment delays to compromise outcomes, but the initial few weeks surrounding the diagnosis are more effectively utilized by time invested in patient education and procedures that contribute to comprehensive treatment planning as opposed to hastily coordinating impulsive, irreversible surgical plans," Dr. Newman wrote.

The study was supported by the Jan Weimer Junior Faculty Chair in Breast Oncology, the Suzanne Pride Bryan Fund for Breast Cancer Research at Stanford Cancer Institute, and the National Cancer Institute. Two authors reported grants from Genentech for other work, but there were no other conflicts of interest disclosed.

The use of bilateral mastectomy has increased significantly in California, but the results from an observational cohort study show it achieves similar mortality reductions to breast-conserving surgery plus radiation, while unilateral mastectomy is associated with higher mortality.

In an analysis of data from nearly 190,000 patients in the population-based California Cancer Registry, no significant differences were found in all-cause mortality between patients who underwent bilateral mastectomy and those who had breast-conserving surgery with radiation (HR, 1.02 [95%CI, 0.94-1.11]); however, unilateral mastectomy was linked to 35% higher all-cause mortality than was breast-conserving surgery with radiation (HR, 1.35 [95% CI, 1.32-1.39]).

Dr. Allison W. Kurian of Stanford (Calif.)University and colleagues also found the rate of bilateral mastectomy had increased 14.3% each year, from 2% of all patients in 1998 to 12.3% in 2011, with it more commonly used among non-Hispanic white women, those with private insurance, and those who received care at a National Cancer Institute–designated cancer center, according to a paper published Sept. 2 in JAMA [doi:10.1001/jama.2014.10707].

"In a time of increasing concern over treatment, the risk-benefit ratio of bilateral mastectomy warrants careful consideration and raises the larger question of how physicians and society should respond to a patient’s preference for a morbid, costly intervention of dubious effectiveness," the authors wrote.

In an accompanying editorial, Dr. Lisa A. Newman of the comprehensive cancer center, University of Michigan, Ann Arbor, said the findings refute patient assumptions that bilateral mastectomy represents their best chance for a cure, and for eliminating the perceived cancer threat to the unaffected breast, and advocated a more calm and considered approach to treatment decision making (JAMA 2014 Sept. 2 [doi:10.1001/jama.2014.11308]).

"Physicians should not permit excessive treatment delays to compromise outcomes, but the initial few weeks surrounding the diagnosis are more effectively utilized by time invested in patient education and procedures that contribute to comprehensive treatment planning as opposed to hastily coordinating impulsive, irreversible surgical plans," Dr. Newman wrote.

The study was supported by the Jan Weimer Junior Faculty Chair in Breast Oncology, the Suzanne Pride Bryan Fund for Breast Cancer Research at Stanford Cancer Institute, and the National Cancer Institute. Two authors reported grants from Genentech for other work, but there were no other conflicts of interest disclosed.

The use of bilateral mastectomy has increased significantly in California, but the results from an observational cohort study show it achieves similar mortality reductions to breast-conserving surgery plus radiation, while unilateral mastectomy is associated with higher mortality.

In an analysis of data from nearly 190,000 patients in the population-based California Cancer Registry, no significant differences were found in all-cause mortality between patients who underwent bilateral mastectomy and those who had breast-conserving surgery with radiation (HR, 1.02 [95%CI, 0.94-1.11]); however, unilateral mastectomy was linked to 35% higher all-cause mortality than was breast-conserving surgery with radiation (HR, 1.35 [95% CI, 1.32-1.39]).

Dr. Allison W. Kurian of Stanford (Calif.)University and colleagues also found the rate of bilateral mastectomy had increased 14.3% each year, from 2% of all patients in 1998 to 12.3% in 2011, with it more commonly used among non-Hispanic white women, those with private insurance, and those who received care at a National Cancer Institute–designated cancer center, according to a paper published Sept. 2 in JAMA [doi:10.1001/jama.2014.10707].

"In a time of increasing concern over treatment, the risk-benefit ratio of bilateral mastectomy warrants careful consideration and raises the larger question of how physicians and society should respond to a patient’s preference for a morbid, costly intervention of dubious effectiveness," the authors wrote.

In an accompanying editorial, Dr. Lisa A. Newman of the comprehensive cancer center, University of Michigan, Ann Arbor, said the findings refute patient assumptions that bilateral mastectomy represents their best chance for a cure, and for eliminating the perceived cancer threat to the unaffected breast, and advocated a more calm and considered approach to treatment decision making (JAMA 2014 Sept. 2 [doi:10.1001/jama.2014.11308]).

"Physicians should not permit excessive treatment delays to compromise outcomes, but the initial few weeks surrounding the diagnosis are more effectively utilized by time invested in patient education and procedures that contribute to comprehensive treatment planning as opposed to hastily coordinating impulsive, irreversible surgical plans," Dr. Newman wrote.

The study was supported by the Jan Weimer Junior Faculty Chair in Breast Oncology, the Suzanne Pride Bryan Fund for Breast Cancer Research at Stanford Cancer Institute, and the National Cancer Institute. Two authors reported grants from Genentech for other work, but there were no other conflicts of interest disclosed.

A new evidence-based practice guideline from the American Society of Clinical Oncology on treating women with advanced breast cancer that is negative for human epidermal growth factor receptor 2 emphasizes that "optimal" chemotherapy regimens may vary considerably between patients.

When choosing treatment for an individual with HER2-negative breast cancer, consider not only the potential efficacy of a therapy but also the potential toxicity, the patient’s performance status and comorbid conditions, history of prior therapy, whether the cancer is indolent or immediately life threatening, and the patient’s preferences and schedule, the guideline states.

That said, the guideline on "Chemotherapy and Targeted Therapy for Women with Human Epidermal Growth Factor Receptor 2-Negative (or unknown) Advanced Breast Cancer" offers some specific recommendations (J. Clin. Oncol. 2014 Sept. 2 [doi:10.1200/JCO.2014.56.7479]).

First-line treatment should be endocrine therapy if the patient has metastatic HER2-negative breast cancer that’s also estrogen receptor positive, unless the disease is immediately life threatening or there is concern about potential resistance to hormone therapy.

Treating with single chemotherapy drugs (in sequential trials, if needed) is preferable to combination chemotherapy for HER2-negative breast cancer in order to limit side effects and help preserve the patient’s quality of life, the guideline states. Although a longer duration of chemotherapy can improve survival, this must be balanced against the treatment’s toxicity.

Use of targeted therapy with bevacizumab, a monoclonal antibody, remains controversial and should only be considered with single-agent chemotherapy for patients with immediately life-threatening disease or severe symptoms, the guideline suggests. Bevacizumab is not approved in the United States to treat breast cancer.

Other targeted therapies have not been shown to improve outcomes in women with advanced HER2-negative breast cancer and should not be used with or instead of chemotherapy in these patients.

Offer palliative care early and throughout the continuum of care, the guideline recommends.

"Although no clear chemotherapy winner emerged, the guideline will help doctors and patients choose the best therapy based on what treatment would be most tolerable and convenient for the patient," Dr. Ann H. Partridge said in an American Society of Clinical Oncology statement. Dr. Partridge cochaired the expert panel that developed the guideline and is director of the Adult Survivorship Program and the Program for Young Women with Breast Cancer at the Dana-Farber Cancer Institute, Boston.

Some of the many treatments available for HER2-negative breast cancer are "unnecessarily toxic," expert panel cochair Dr. Ian E. Smith said in the ASCO statement. "Breast cancer can often be controlled with less intensive approaches that offer a better quality of life," said Dr. Smith, a professor of cancer medicine at Royal Marsden Hospital, London.

ASCO’s consensus-driven expert panel reviewed randomized studies in the medical literature from 1993 through May 2013 and used the 2009 systematic review by the National Collaborating Centre for Cancer in England as a starting point for what’s known. The panel considered 79 studies, including 20 systematic reviews or meta-analyses, 30 trials of first-line treatments, and 29 trials of second-line or subsequent treatments.

A majority of patients with advanced breast cancer have HER2-negative disease, for which development of targeted therapies is in the early stages. The current speed of research progress in cancer genomics and potential targets of drug therapy is likely to produce new targeted therapies soon to enhance or replace chemotherapy, the guideline authors predicted.

Even then, collaboration between physician and patient to find the optimal approach will remain key. "Given the heterogeneity of breast cancer, even when restricted to HER2-negative disease, it is also possible that ‘one size will never fit all’ and that there is no best treatment for most patients," they wrote.

Dr. Partridge and Dr. Smith reported having no financial disclosures. Disclosures for several of their coauthors who reported having associations with pharmaceutical companies are available with the article online.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

A new evidence-based practice guideline from the American Society of Clinical Oncology on treating women with advanced breast cancer that is negative for human epidermal growth factor receptor 2 emphasizes that "optimal" chemotherapy regimens may vary considerably between patients.

When choosing treatment for an individual with HER2-negative breast cancer, consider not only the potential efficacy of a therapy but also the potential toxicity, the patient’s performance status and comorbid conditions, history of prior therapy, whether the cancer is indolent or immediately life threatening, and the patient’s preferences and schedule, the guideline states.

That said, the guideline on "Chemotherapy and Targeted Therapy for Women with Human Epidermal Growth Factor Receptor 2-Negative (or unknown) Advanced Breast Cancer" offers some specific recommendations (J. Clin. Oncol. 2014 Sept. 2 [doi:10.1200/JCO.2014.56.7479]).

First-line treatment should be endocrine therapy if the patient has metastatic HER2-negative breast cancer that’s also estrogen receptor positive, unless the disease is immediately life threatening or there is concern about potential resistance to hormone therapy.

Treating with single chemotherapy drugs (in sequential trials, if needed) is preferable to combination chemotherapy for HER2-negative breast cancer in order to limit side effects and help preserve the patient’s quality of life, the guideline states. Although a longer duration of chemotherapy can improve survival, this must be balanced against the treatment’s toxicity.

Use of targeted therapy with bevacizumab, a monoclonal antibody, remains controversial and should only be considered with single-agent chemotherapy for patients with immediately life-threatening disease or severe symptoms, the guideline suggests. Bevacizumab is not approved in the United States to treat breast cancer.

Other targeted therapies have not been shown to improve outcomes in women with advanced HER2-negative breast cancer and should not be used with or instead of chemotherapy in these patients.

Offer palliative care early and throughout the continuum of care, the guideline recommends.

"Although no clear chemotherapy winner emerged, the guideline will help doctors and patients choose the best therapy based on what treatment would be most tolerable and convenient for the patient," Dr. Ann H. Partridge said in an American Society of Clinical Oncology statement. Dr. Partridge cochaired the expert panel that developed the guideline and is director of the Adult Survivorship Program and the Program for Young Women with Breast Cancer at the Dana-Farber Cancer Institute, Boston.

Some of the many treatments available for HER2-negative breast cancer are "unnecessarily toxic," expert panel cochair Dr. Ian E. Smith said in the ASCO statement. "Breast cancer can often be controlled with less intensive approaches that offer a better quality of life," said Dr. Smith, a professor of cancer medicine at Royal Marsden Hospital, London.

ASCO’s consensus-driven expert panel reviewed randomized studies in the medical literature from 1993 through May 2013 and used the 2009 systematic review by the National Collaborating Centre for Cancer in England as a starting point for what’s known. The panel considered 79 studies, including 20 systematic reviews or meta-analyses, 30 trials of first-line treatments, and 29 trials of second-line or subsequent treatments.

A majority of patients with advanced breast cancer have HER2-negative disease, for which development of targeted therapies is in the early stages. The current speed of research progress in cancer genomics and potential targets of drug therapy is likely to produce new targeted therapies soon to enhance or replace chemotherapy, the guideline authors predicted.

Even then, collaboration between physician and patient to find the optimal approach will remain key. "Given the heterogeneity of breast cancer, even when restricted to HER2-negative disease, it is also possible that ‘one size will never fit all’ and that there is no best treatment for most patients," they wrote.

Dr. Partridge and Dr. Smith reported having no financial disclosures. Disclosures for several of their coauthors who reported having associations with pharmaceutical companies are available with the article online.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

A new evidence-based practice guideline from the American Society of Clinical Oncology on treating women with advanced breast cancer that is negative for human epidermal growth factor receptor 2 emphasizes that "optimal" chemotherapy regimens may vary considerably between patients.

When choosing treatment for an individual with HER2-negative breast cancer, consider not only the potential efficacy of a therapy but also the potential toxicity, the patient’s performance status and comorbid conditions, history of prior therapy, whether the cancer is indolent or immediately life threatening, and the patient’s preferences and schedule, the guideline states.

That said, the guideline on "Chemotherapy and Targeted Therapy for Women with Human Epidermal Growth Factor Receptor 2-Negative (or unknown) Advanced Breast Cancer" offers some specific recommendations (J. Clin. Oncol. 2014 Sept. 2 [doi:10.1200/JCO.2014.56.7479]).

First-line treatment should be endocrine therapy if the patient has metastatic HER2-negative breast cancer that’s also estrogen receptor positive, unless the disease is immediately life threatening or there is concern about potential resistance to hormone therapy.

Treating with single chemotherapy drugs (in sequential trials, if needed) is preferable to combination chemotherapy for HER2-negative breast cancer in order to limit side effects and help preserve the patient’s quality of life, the guideline states. Although a longer duration of chemotherapy can improve survival, this must be balanced against the treatment’s toxicity.

Use of targeted therapy with bevacizumab, a monoclonal antibody, remains controversial and should only be considered with single-agent chemotherapy for patients with immediately life-threatening disease or severe symptoms, the guideline suggests. Bevacizumab is not approved in the United States to treat breast cancer.

Other targeted therapies have not been shown to improve outcomes in women with advanced HER2-negative breast cancer and should not be used with or instead of chemotherapy in these patients.

Offer palliative care early and throughout the continuum of care, the guideline recommends.

"Although no clear chemotherapy winner emerged, the guideline will help doctors and patients choose the best therapy based on what treatment would be most tolerable and convenient for the patient," Dr. Ann H. Partridge said in an American Society of Clinical Oncology statement. Dr. Partridge cochaired the expert panel that developed the guideline and is director of the Adult Survivorship Program and the Program for Young Women with Breast Cancer at the Dana-Farber Cancer Institute, Boston.

Some of the many treatments available for HER2-negative breast cancer are "unnecessarily toxic," expert panel cochair Dr. Ian E. Smith said in the ASCO statement. "Breast cancer can often be controlled with less intensive approaches that offer a better quality of life," said Dr. Smith, a professor of cancer medicine at Royal Marsden Hospital, London.

ASCO’s consensus-driven expert panel reviewed randomized studies in the medical literature from 1993 through May 2013 and used the 2009 systematic review by the National Collaborating Centre for Cancer in England as a starting point for what’s known. The panel considered 79 studies, including 20 systematic reviews or meta-analyses, 30 trials of first-line treatments, and 29 trials of second-line or subsequent treatments.

A majority of patients with advanced breast cancer have HER2-negative disease, for which development of targeted therapies is in the early stages. The current speed of research progress in cancer genomics and potential targets of drug therapy is likely to produce new targeted therapies soon to enhance or replace chemotherapy, the guideline authors predicted.

Even then, collaboration between physician and patient to find the optimal approach will remain key. "Given the heterogeneity of breast cancer, even when restricted to HER2-negative disease, it is also possible that ‘one size will never fit all’ and that there is no best treatment for most patients," they wrote.

Dr. Partridge and Dr. Smith reported having no financial disclosures. Disclosures for several of their coauthors who reported having associations with pharmaceutical companies are available with the article online.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Open breast biopsy accounted for 34% of breast biopsies in 25,965 U.S. inpatients between 2008 and 2010, a retrospective study found.

The finding suggests that minimally invasive breast biopsy techniques are underutilized, with a national rate that’s far off the widely acknowledge goal of having at least 90% of biopsies for suspicious breast lesions be minimally invasive, Dr. Linda Adepoju reported.

Most breast biopsies are performed in outpatient settings. Although the study analyzed a national data sample for hospitalized patients, the rate of open breast biopsy is consistent with previous studies of outpatient databases for individual institutions or states that have reported rates of open breast biopsy from 24% to 36%, noted Dr. Adepoju of the University of Toledo (Ohio).

She and her associates analyzed data from 46 states in the Healthcare Cost and Utilization Project National Inpatient Sample for 2008-2010, excluding 222 cases in which an open breast biopsy and minimally invasive breast biopsy were performed during the same hospital stay.

Open breast biopsy rates were significantly higher in women aged 49 years or younger (47%), compared with older women (29%), and in Asian women (40%) or Hispanic women (41%), compared with white women (34%) or black women (31%). Open breast biopsy also was significantly more likely in women who had private insurance than in women covered by Medicaid or Medicare – 41% vs. 31% (Am. J. Surg. 2014;208:382-90).

The type and location of hospital also was associated with open biopsy rates, with higher rates in small, private, rural, and/or nonteaching hospitals.

"Interventions targeting small, rural, and nonteaching hospitals could significantly decrease hospital costs and improve the overall quality of breast care," Dr. Adepoju and her associates commented, but "we must be sensitive" to the needs and limitations of various health care delivery settings, they added.

"A critical access hospital in rural Ohio may not be able to afford a mammographer and stereotactic equipment" for minimally invasive breast biopsy. Previous data "are clear that patients preferably seek their care in and near their community. Given workforce shortages and the current economic climate, this may mean accepting higher open breast biopsy rates in rural America," the investigators concluded.

Patients who had open breast biopsies in the current study were more likely to need more than one biopsy for diagnosis (1.2%), compared with women who had minimally invasive breast biopsies (0.5%). Hematoma drainage was needed in 1.4% of patients after open breast biopsy and 0.6% after minimally invasive biopsy. Open breast biopsy also was more expensive, based on analysis of data from the University of Toledo, averaging $1,700 in Medicare reimbursement, compared with $300-$1,100 for minimally invasive breast biopsy, depending on the specific procedure, Dr. Adepoju reported.

Previous data have shown that minimally invasive breast biopsies are less expensive, less scarring, require less recovery time, cause fewer complications, reduce the time between diagnosis and definitive treatment, produce fewer positive margins, and facilitate preoperative multidisciplinary treatment planning, compared with open breast biopsies.

The report from the third international consensus conference on image-detected breast cancer in 2009 called minimally invasive breast biopsy a best practice that should be the gold standard for initial diagnosis and proposed a goal of limiting open breast biopsy to 5%-10% of cases (J. Am. Coll. Surg. 2009;209:504-20).

Dr. Adepoju reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Open breast biopsy accounted for 34% of breast biopsies in 25,965 U.S. inpatients between 2008 and 2010, a retrospective study found.

The finding suggests that minimally invasive breast biopsy techniques are underutilized, with a national rate that’s far off the widely acknowledge goal of having at least 90% of biopsies for suspicious breast lesions be minimally invasive, Dr. Linda Adepoju reported.

Most breast biopsies are performed in outpatient settings. Although the study analyzed a national data sample for hospitalized patients, the rate of open breast biopsy is consistent with previous studies of outpatient databases for individual institutions or states that have reported rates of open breast biopsy from 24% to 36%, noted Dr. Adepoju of the University of Toledo (Ohio).

She and her associates analyzed data from 46 states in the Healthcare Cost and Utilization Project National Inpatient Sample for 2008-2010, excluding 222 cases in which an open breast biopsy and minimally invasive breast biopsy were performed during the same hospital stay.

Open breast biopsy rates were significantly higher in women aged 49 years or younger (47%), compared with older women (29%), and in Asian women (40%) or Hispanic women (41%), compared with white women (34%) or black women (31%). Open breast biopsy also was significantly more likely in women who had private insurance than in women covered by Medicaid or Medicare – 41% vs. 31% (Am. J. Surg. 2014;208:382-90).

The type and location of hospital also was associated with open biopsy rates, with higher rates in small, private, rural, and/or nonteaching hospitals.

"Interventions targeting small, rural, and nonteaching hospitals could significantly decrease hospital costs and improve the overall quality of breast care," Dr. Adepoju and her associates commented, but "we must be sensitive" to the needs and limitations of various health care delivery settings, they added.

"A critical access hospital in rural Ohio may not be able to afford a mammographer and stereotactic equipment" for minimally invasive breast biopsy. Previous data "are clear that patients preferably seek their care in and near their community. Given workforce shortages and the current economic climate, this may mean accepting higher open breast biopsy rates in rural America," the investigators concluded.

Patients who had open breast biopsies in the current study were more likely to need more than one biopsy for diagnosis (1.2%), compared with women who had minimally invasive breast biopsies (0.5%). Hematoma drainage was needed in 1.4% of patients after open breast biopsy and 0.6% after minimally invasive biopsy. Open breast biopsy also was more expensive, based on analysis of data from the University of Toledo, averaging $1,700 in Medicare reimbursement, compared with $300-$1,100 for minimally invasive breast biopsy, depending on the specific procedure, Dr. Adepoju reported.

Previous data have shown that minimally invasive breast biopsies are less expensive, less scarring, require less recovery time, cause fewer complications, reduce the time between diagnosis and definitive treatment, produce fewer positive margins, and facilitate preoperative multidisciplinary treatment planning, compared with open breast biopsies.

The report from the third international consensus conference on image-detected breast cancer in 2009 called minimally invasive breast biopsy a best practice that should be the gold standard for initial diagnosis and proposed a goal of limiting open breast biopsy to 5%-10% of cases (J. Am. Coll. Surg. 2009;209:504-20).

Dr. Adepoju reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Open breast biopsy accounted for 34% of breast biopsies in 25,965 U.S. inpatients between 2008 and 2010, a retrospective study found.

The finding suggests that minimally invasive breast biopsy techniques are underutilized, with a national rate that’s far off the widely acknowledge goal of having at least 90% of biopsies for suspicious breast lesions be minimally invasive, Dr. Linda Adepoju reported.

Most breast biopsies are performed in outpatient settings. Although the study analyzed a national data sample for hospitalized patients, the rate of open breast biopsy is consistent with previous studies of outpatient databases for individual institutions or states that have reported rates of open breast biopsy from 24% to 36%, noted Dr. Adepoju of the University of Toledo (Ohio).

She and her associates analyzed data from 46 states in the Healthcare Cost and Utilization Project National Inpatient Sample for 2008-2010, excluding 222 cases in which an open breast biopsy and minimally invasive breast biopsy were performed during the same hospital stay.

Open breast biopsy rates were significantly higher in women aged 49 years or younger (47%), compared with older women (29%), and in Asian women (40%) or Hispanic women (41%), compared with white women (34%) or black women (31%). Open breast biopsy also was significantly more likely in women who had private insurance than in women covered by Medicaid or Medicare – 41% vs. 31% (Am. J. Surg. 2014;208:382-90).

The type and location of hospital also was associated with open biopsy rates, with higher rates in small, private, rural, and/or nonteaching hospitals.

"Interventions targeting small, rural, and nonteaching hospitals could significantly decrease hospital costs and improve the overall quality of breast care," Dr. Adepoju and her associates commented, but "we must be sensitive" to the needs and limitations of various health care delivery settings, they added.

"A critical access hospital in rural Ohio may not be able to afford a mammographer and stereotactic equipment" for minimally invasive breast biopsy. Previous data "are clear that patients preferably seek their care in and near their community. Given workforce shortages and the current economic climate, this may mean accepting higher open breast biopsy rates in rural America," the investigators concluded.

Patients who had open breast biopsies in the current study were more likely to need more than one biopsy for diagnosis (1.2%), compared with women who had minimally invasive breast biopsies (0.5%). Hematoma drainage was needed in 1.4% of patients after open breast biopsy and 0.6% after minimally invasive biopsy. Open breast biopsy also was more expensive, based on analysis of data from the University of Toledo, averaging $1,700 in Medicare reimbursement, compared with $300-$1,100 for minimally invasive breast biopsy, depending on the specific procedure, Dr. Adepoju reported.

Previous data have shown that minimally invasive breast biopsies are less expensive, less scarring, require less recovery time, cause fewer complications, reduce the time between diagnosis and definitive treatment, produce fewer positive margins, and facilitate preoperative multidisciplinary treatment planning, compared with open breast biopsies.

The report from the third international consensus conference on image-detected breast cancer in 2009 called minimally invasive breast biopsy a best practice that should be the gold standard for initial diagnosis and proposed a goal of limiting open breast biopsy to 5%-10% of cases (J. Am. Coll. Surg. 2009;209:504-20).

Dr. Adepoju reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Treatment with tumor necrosis factor inhibitors does not appear to increase the rate of breast cancer recurrence among patients with rheumatoid arthritis, according to findings from a Swedish case-control study.

The study’s results help to allay concerns about the potential for tumor necrosis factor (TNF) inhibitors to promote cancer recurrence, but it still leaves the agents’ possible effect on much more recently diagnosed cancer or cancers with poor prognosis unknown, said lead investigator Dr. Pauline Raaschou of the Karolinska Institute, Stockholm, and her colleagues in the ARTIS Study Group.

Although two previous studies have examined the risk of recurrence of any type of cancer in patients treated with a TNF inhibitor, it was unclear to the investigators how much the baseline risk of recurrence played a role and how much "channeling" of high-risk patients away from TNF inhibitors has potentially contributed to selection bias in such studies. Breast cancer seemed an ideal cancer type to study in this regard, the investigators said, because of women’s high lifetime risk and the dovetailing of peak age of onset of both breast cancer and RA at around age 60 years.

The researchers matched 120 patients who were treated with TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) to 120 patients who had never received treatment with a biologic. The patients had started TNF inhibitors or began follow-up a median of 9.4 years after their breast cancer diagnosis. The patients had a mean age of 66-67 years and their cancers were in remission at the start of follow-up (Ann. Rheum. Dis. 2014 Aug. 8 [doi:10.1136/annrheumdis-2014-205745]).

During 592 person-years of follow-up, nine patients treated with a TNF inhibitor developed a breast cancer recurrence for a crude incidence rate of 15/1,000 person-years, compared with nine of the biologic-naive patients during 550 person-years of follow-up for a rate of 16/1,000 person-years. This gave a hazard ratio of 0.8 with a 95% confidence interval of 0.3-2.1.

The risk did not change appreciably in different models that adjusted for small differences in prognostic factors for breast cancer recurrence and RA-related characteristics. There also were no differences in the risk of recurrence between individuals with a history of breast cancer within 5 years or later – a time frame in which many guidelines recommend using caution in starting TNF inhibitors – but only 15% of the patients started a TNF inhibitor within 5 years of their breast cancer, according to the investigators.

Dr. Raaschou and her associates noted that although their study is the largest on the topic to date, it still has limited power because at an alpha of .05, "a study of our design would require approximately 120 patients in each treatment group [i.e., our sample size] to have 80% power to detect a doubled risk, but 350 patients in each treatment group to detect a 50% increased risk."

This research was funded by a variety of Swedish medical societies, foundations, and programs. One author reported receiving research grants from Pfizer and AstraZeneca as part of a public-private research consortium and speaker’s honoraria from Merck. The Swedish Biologics Register, ARTIS, is maintained in part by funding from Abbott Laboratories, Bristol-Myers Squibb, Merck, Pfizer, Roche, SOBI, and UCB.

jevans@frontlinemedcom.com

Treatment with tumor necrosis factor inhibitors does not appear to increase the rate of breast cancer recurrence among patients with rheumatoid arthritis, according to findings from a Swedish case-control study.

The study’s results help to allay concerns about the potential for tumor necrosis factor (TNF) inhibitors to promote cancer recurrence, but it still leaves the agents’ possible effect on much more recently diagnosed cancer or cancers with poor prognosis unknown, said lead investigator Dr. Pauline Raaschou of the Karolinska Institute, Stockholm, and her colleagues in the ARTIS Study Group.

Although two previous studies have examined the risk of recurrence of any type of cancer in patients treated with a TNF inhibitor, it was unclear to the investigators how much the baseline risk of recurrence played a role and how much "channeling" of high-risk patients away from TNF inhibitors has potentially contributed to selection bias in such studies. Breast cancer seemed an ideal cancer type to study in this regard, the investigators said, because of women’s high lifetime risk and the dovetailing of peak age of onset of both breast cancer and RA at around age 60 years.

The researchers matched 120 patients who were treated with TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) to 120 patients who had never received treatment with a biologic. The patients had started TNF inhibitors or began follow-up a median of 9.4 years after their breast cancer diagnosis. The patients had a mean age of 66-67 years and their cancers were in remission at the start of follow-up (Ann. Rheum. Dis. 2014 Aug. 8 [doi:10.1136/annrheumdis-2014-205745]).

During 592 person-years of follow-up, nine patients treated with a TNF inhibitor developed a breast cancer recurrence for a crude incidence rate of 15/1,000 person-years, compared with nine of the biologic-naive patients during 550 person-years of follow-up for a rate of 16/1,000 person-years. This gave a hazard ratio of 0.8 with a 95% confidence interval of 0.3-2.1.

The risk did not change appreciably in different models that adjusted for small differences in prognostic factors for breast cancer recurrence and RA-related characteristics. There also were no differences in the risk of recurrence between individuals with a history of breast cancer within 5 years or later – a time frame in which many guidelines recommend using caution in starting TNF inhibitors – but only 15% of the patients started a TNF inhibitor within 5 years of their breast cancer, according to the investigators.

Dr. Raaschou and her associates noted that although their study is the largest on the topic to date, it still has limited power because at an alpha of .05, "a study of our design would require approximately 120 patients in each treatment group [i.e., our sample size] to have 80% power to detect a doubled risk, but 350 patients in each treatment group to detect a 50% increased risk."

This research was funded by a variety of Swedish medical societies, foundations, and programs. One author reported receiving research grants from Pfizer and AstraZeneca as part of a public-private research consortium and speaker’s honoraria from Merck. The Swedish Biologics Register, ARTIS, is maintained in part by funding from Abbott Laboratories, Bristol-Myers Squibb, Merck, Pfizer, Roche, SOBI, and UCB.

jevans@frontlinemedcom.com

Treatment with tumor necrosis factor inhibitors does not appear to increase the rate of breast cancer recurrence among patients with rheumatoid arthritis, according to findings from a Swedish case-control study.

The study’s results help to allay concerns about the potential for tumor necrosis factor (TNF) inhibitors to promote cancer recurrence, but it still leaves the agents’ possible effect on much more recently diagnosed cancer or cancers with poor prognosis unknown, said lead investigator Dr. Pauline Raaschou of the Karolinska Institute, Stockholm, and her colleagues in the ARTIS Study Group.

Although two previous studies have examined the risk of recurrence of any type of cancer in patients treated with a TNF inhibitor, it was unclear to the investigators how much the baseline risk of recurrence played a role and how much "channeling" of high-risk patients away from TNF inhibitors has potentially contributed to selection bias in such studies. Breast cancer seemed an ideal cancer type to study in this regard, the investigators said, because of women’s high lifetime risk and the dovetailing of peak age of onset of both breast cancer and RA at around age 60 years.

The researchers matched 120 patients who were treated with TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) to 120 patients who had never received treatment with a biologic. The patients had started TNF inhibitors or began follow-up a median of 9.4 years after their breast cancer diagnosis. The patients had a mean age of 66-67 years and their cancers were in remission at the start of follow-up (Ann. Rheum. Dis. 2014 Aug. 8 [doi:10.1136/annrheumdis-2014-205745]).

During 592 person-years of follow-up, nine patients treated with a TNF inhibitor developed a breast cancer recurrence for a crude incidence rate of 15/1,000 person-years, compared with nine of the biologic-naive patients during 550 person-years of follow-up for a rate of 16/1,000 person-years. This gave a hazard ratio of 0.8 with a 95% confidence interval of 0.3-2.1.

The risk did not change appreciably in different models that adjusted for small differences in prognostic factors for breast cancer recurrence and RA-related characteristics. There also were no differences in the risk of recurrence between individuals with a history of breast cancer within 5 years or later – a time frame in which many guidelines recommend using caution in starting TNF inhibitors – but only 15% of the patients started a TNF inhibitor within 5 years of their breast cancer, according to the investigators.

Dr. Raaschou and her associates noted that although their study is the largest on the topic to date, it still has limited power because at an alpha of .05, "a study of our design would require approximately 120 patients in each treatment group [i.e., our sample size] to have 80% power to detect a doubled risk, but 350 patients in each treatment group to detect a 50% increased risk."

This research was funded by a variety of Swedish medical societies, foundations, and programs. One author reported receiving research grants from Pfizer and AstraZeneca as part of a public-private research consortium and speaker’s honoraria from Merck. The Swedish Biologics Register, ARTIS, is maintained in part by funding from Abbott Laboratories, Bristol-Myers Squibb, Merck, Pfizer, Roche, SOBI, and UCB.

jevans@frontlinemedcom.com

Three to four years of therapy with the bisphosphonates alendronate and zoledronic acid, taken at doses used to treat osteoporosis, did not decrease the risk of incident breast cancer in postmenopausal women, according to a report published online Aug. 11 in JAMA Internal Medicine.

In a post hoc analysis of data from two large multicenter, randomized, double-blind, controlled clinical trials assessing the effectiveness of alendronate or zoledronic acid for osteoporosis, the development of incident breast cancer was not significantly different between women taking the drugs and women taking placebo, said Trisha F. Hue, Ph.D., of the department of epidemiology and biostatistics at the University of California, San Francisco, and her associates.

Numerous previous observational studies, as well as a metaanalysis pooling the data from several observational studies, had shown that bisphosphonates taken for osteoporosis significantly lowered the risk of breast cancer by 32%-39%. Their findings, however, may have been confounded by indication, because other conditions in postmenopausal women – notably, low levels of estradiol and high levels of sex hormone–binding globulin (SHBG) – are strongly associated both with low bone density, fractures, and bone loss with a low risk of ER-positive breast cancer, Dr. Hue and her associates said. Thus, they suggested, the postmenopausal women who are most likely to be given bisphosphonates for bone health already have a lower risk of breast cancer.

Such confounding can be averted by using a randomized trial design, so Dr. Hue and her colleagues assessed whether bisphosphonates reduced incident breast cancer by analyzing data from the Fracture Intervention Trial (FIT) and the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT).

Among the 6,194 FIT participants in this study, there were 103 cases of invasive breast cancer during a mean of 3.8 years of follow-up. The incidence of breast cancer was 1.8% (57 women) among women taking alendronate and 1.5% (46 women) in those taking placebo, a nonsignificant difference in favor of placebo.

Among the 7,580 HORIZON-PFT participants in this study, there were 62 cases of invasive breast cancer during 3 years of follow-up. The incidence of breast cancer was 0.9% (33 women) among women taking zoledronic acid and 0.8% (29 women) among those taking placebo, which was, again, a nonsignificant difference in favor of placebo, the investigators said (JAMA Intern. Med. 2014 Aug. 11 [doi:10.1001/jamainternmed.2014.3634]).

The total of breast cancer cases was relatively small, so Dr. Hue and her associates pooled the data from both studies to increase the sample size. The combined incidence of breast cancer was 1.3% (90 women) taking bisphosphonates and 1.1% (75 women) taking placebo – again, a nonsignificant difference favoring placebo.

The discrepancy between these findings from randomized controlled trials and the results of previous observational studies illustrates "the hazard of drawing conclusions about treatment effects from observational studies (even those that are very well done)" and highlights the value of confirming such findings in randomized controlled trials, Dr. Hue and her associates said.

This study received no industry support. FIT was supported by Merck, and HORIZON-PFT was supported by Novartis; both companies were involved in data collection and management. Dr. Hue reported no potential financial conflicts of interest. One of her associates reported serving as a consultant for Merck Sharpe & Dohme.

Three to four years of therapy with the bisphosphonates alendronate and zoledronic acid, taken at doses used to treat osteoporosis, did not decrease the risk of incident breast cancer in postmenopausal women, according to a report published online Aug. 11 in JAMA Internal Medicine.

In a post hoc analysis of data from two large multicenter, randomized, double-blind, controlled clinical trials assessing the effectiveness of alendronate or zoledronic acid for osteoporosis, the development of incident breast cancer was not significantly different between women taking the drugs and women taking placebo, said Trisha F. Hue, Ph.D., of the department of epidemiology and biostatistics at the University of California, San Francisco, and her associates.

Numerous previous observational studies, as well as a metaanalysis pooling the data from several observational studies, had shown that bisphosphonates taken for osteoporosis significantly lowered the risk of breast cancer by 32%-39%. Their findings, however, may have been confounded by indication, because other conditions in postmenopausal women – notably, low levels of estradiol and high levels of sex hormone–binding globulin (SHBG) – are strongly associated both with low bone density, fractures, and bone loss with a low risk of ER-positive breast cancer, Dr. Hue and her associates said. Thus, they suggested, the postmenopausal women who are most likely to be given bisphosphonates for bone health already have a lower risk of breast cancer.

Such confounding can be averted by using a randomized trial design, so Dr. Hue and her colleagues assessed whether bisphosphonates reduced incident breast cancer by analyzing data from the Fracture Intervention Trial (FIT) and the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT).

Among the 6,194 FIT participants in this study, there were 103 cases of invasive breast cancer during a mean of 3.8 years of follow-up. The incidence of breast cancer was 1.8% (57 women) among women taking alendronate and 1.5% (46 women) in those taking placebo, a nonsignificant difference in favor of placebo.

Among the 7,580 HORIZON-PFT participants in this study, there were 62 cases of invasive breast cancer during 3 years of follow-up. The incidence of breast cancer was 0.9% (33 women) among women taking zoledronic acid and 0.8% (29 women) among those taking placebo, which was, again, a nonsignificant difference in favor of placebo, the investigators said (JAMA Intern. Med. 2014 Aug. 11 [doi:10.1001/jamainternmed.2014.3634]).

The total of breast cancer cases was relatively small, so Dr. Hue and her associates pooled the data from both studies to increase the sample size. The combined incidence of breast cancer was 1.3% (90 women) taking bisphosphonates and 1.1% (75 women) taking placebo – again, a nonsignificant difference favoring placebo.

The discrepancy between these findings from randomized controlled trials and the results of previous observational studies illustrates "the hazard of drawing conclusions about treatment effects from observational studies (even those that are very well done)" and highlights the value of confirming such findings in randomized controlled trials, Dr. Hue and her associates said.

This study received no industry support. FIT was supported by Merck, and HORIZON-PFT was supported by Novartis; both companies were involved in data collection and management. Dr. Hue reported no potential financial conflicts of interest. One of her associates reported serving as a consultant for Merck Sharpe & Dohme.

Three to four years of therapy with the bisphosphonates alendronate and zoledronic acid, taken at doses used to treat osteoporosis, did not decrease the risk of incident breast cancer in postmenopausal women, according to a report published online Aug. 11 in JAMA Internal Medicine.

In a post hoc analysis of data from two large multicenter, randomized, double-blind, controlled clinical trials assessing the effectiveness of alendronate or zoledronic acid for osteoporosis, the development of incident breast cancer was not significantly different between women taking the drugs and women taking placebo, said Trisha F. Hue, Ph.D., of the department of epidemiology and biostatistics at the University of California, San Francisco, and her associates.

Numerous previous observational studies, as well as a metaanalysis pooling the data from several observational studies, had shown that bisphosphonates taken for osteoporosis significantly lowered the risk of breast cancer by 32%-39%. Their findings, however, may have been confounded by indication, because other conditions in postmenopausal women – notably, low levels of estradiol and high levels of sex hormone–binding globulin (SHBG) – are strongly associated both with low bone density, fractures, and bone loss with a low risk of ER-positive breast cancer, Dr. Hue and her associates said. Thus, they suggested, the postmenopausal women who are most likely to be given bisphosphonates for bone health already have a lower risk of breast cancer.

Such confounding can be averted by using a randomized trial design, so Dr. Hue and her colleagues assessed whether bisphosphonates reduced incident breast cancer by analyzing data from the Fracture Intervention Trial (FIT) and the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT).

Among the 6,194 FIT participants in this study, there were 103 cases of invasive breast cancer during a mean of 3.8 years of follow-up. The incidence of breast cancer was 1.8% (57 women) among women taking alendronate and 1.5% (46 women) in those taking placebo, a nonsignificant difference in favor of placebo.

Among the 7,580 HORIZON-PFT participants in this study, there were 62 cases of invasive breast cancer during 3 years of follow-up. The incidence of breast cancer was 0.9% (33 women) among women taking zoledronic acid and 0.8% (29 women) among those taking placebo, which was, again, a nonsignificant difference in favor of placebo, the investigators said (JAMA Intern. Med. 2014 Aug. 11 [doi:10.1001/jamainternmed.2014.3634]).

The total of breast cancer cases was relatively small, so Dr. Hue and her associates pooled the data from both studies to increase the sample size. The combined incidence of breast cancer was 1.3% (90 women) taking bisphosphonates and 1.1% (75 women) taking placebo – again, a nonsignificant difference favoring placebo.

The discrepancy between these findings from randomized controlled trials and the results of previous observational studies illustrates "the hazard of drawing conclusions about treatment effects from observational studies (even those that are very well done)" and highlights the value of confirming such findings in randomized controlled trials, Dr. Hue and her associates said.

This study received no industry support. FIT was supported by Merck, and HORIZON-PFT was supported by Novartis; both companies were involved in data collection and management. Dr. Hue reported no potential financial conflicts of interest. One of her associates reported serving as a consultant for Merck Sharpe & Dohme.