Breast Cancer

Combined treatment with everolimus and exemestane more than doubled median progression-free survival in postmenopausal women with hormone receptor–positive breast cancer that had advanced previously after hormone therapy.

Compared with exemestane (Aromasin) and placebo, the everolimus (Afinitor) and exemestane combination increased the median progression-free interval from 3.2 months to 7.4 months, according to Dr. Gabriel N. Hortobagyi, who will present new data from the phase III BOLERO-2 trial at the San Antonio Breast Cancer Symposium.

Moreover, the clinical benefit rate doubled from 25.5% to 50.5%, as twice as many women had either a complete or partial response or stable disease exceeding 6 months, Dr. Hortobagyi, professor and chair of Breast Medical Oncology at the University of Texas M.D. Anderson Cancer Center, will report.

The BOLERO-2 findings could shift standard treatment of therapy-resistant patients from sequential use of aromatase inhibitors to simultaneous inhibition of the estrogen-signaling pathway with an aromatase inhibitor such as exemestane and of the PI3-kinase/AKT/mTOR pathway with everolimus.

"For the first time in a large phase III trial, we have demonstrated that this dual-attack is more effective than a single endocrine treatment for patients who have received prior endocrine therapy," Dr. Hortobagyi said in a press statement.

The gain from addition of an mTOR inhibitor comes with a higher incidence of adverse events such as stomatitis, anemia, and dyspnea in patients taking the combination. "In the current study, a high percentage of patients discontinued everolimus because of lack of tolerability," the BOLERO-2 researchers wrote in a report published online Dec. 7 in the New England Journal of Medicine.

"The longer treatment duration in the combination therapy group might have contributed to the high discontinuation rate. Careful monitoring of patients and increased physician awareness of the safety profile of everolimus are warranted," wrote lead author José Baselga, MD, PhD, chief of hematology/oncology and associate director of the Massachusetts General Hospital Cancer Center, and his co-authors.

Between June 2009 and January 2011, Dr. Baselga and his associates at 189 centers in 24 countries randomized 485 women with HR-positive breast cancer refractory to nonsteroidal aromatase inhibitors to receive a combination of everolimus and exemestane (combination therapy group), and 239 women to receive exemestane plus placebo (exemestane-alone group) in the Breast Cancer Trials of Oral Everolimus–2 (BOLERO-2). The mean age of patients was 62 years, 56% had visceral involvement, and 76% had bone metastasis. The primary end point was progression-free survival (N. Engl. J. Med. 2011 Dec. 7 [doi: 10.1056/NEJMoa1109653]).

Dr. Baselga and his associates reported that previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse event was stomatitis (8% in the combination therapy group vs. 1% in the exemestane-alone group), followed by anemia (6% vs. less than 1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. less than 1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%).

"Our positive results are consistent with the outcomes of two other studies of everolimus and antiestrogen therapy in patients with HR-positive breast cancer ... [and] the magnitude of the observed benefit compares favorably with that of the limited options available to this group of patients," the researchers wrote.

Nearly twice as many adverse events were reported among patients in the combination therapy group compared with the exemestane-alone group (23% vs. 12%). Dr. Baselga and his associates observed that "a higher percentage of patients discontinued everolimus in the combination therapy group than discontinued placebo in the control group because of adverse events (19% vs. 4%), and withdrawal of consent (5% vs. 2%). For exemestane discontinuation, the corresponding numbers were 7% versus 3% and 7% versus 2%."

The researchers went on to note that the adverse events seen in the combination therapy group "are consistent with those reported with everolimus and other rapamycin analogues and include stomatitis, fatigue and asthenia, diarrhea, cough, pyrexia, and hyperglycemia."

The study was sponsored by Novartis. Dr. Baselga disclosed that he is a member of the scientific advisory board for Novartis and numerous other companies including Merck and Bayer. He also has accepted consulting fees from numerous pharmaceutical companies. Dr. Hortobagyi reported receiving research funds from and serving as a consultant for Novartis. Some of the other researchers have ties to a variety of pharmaceutical companies.

Combined treatment with everolimus and exemestane more than doubled median progression-free survival in postmenopausal women with hormone receptor–positive breast cancer that had advanced previously after hormone therapy.

Compared with exemestane (Aromasin) and placebo, the everolimus (Afinitor) and exemestane combination increased the median progression-free interval from 3.2 months to 7.4 months, according to Dr. Gabriel N. Hortobagyi, who will present new data from the phase III BOLERO-2 trial at the San Antonio Breast Cancer Symposium.

Moreover, the clinical benefit rate doubled from 25.5% to 50.5%, as twice as many women had either a complete or partial response or stable disease exceeding 6 months, Dr. Hortobagyi, professor and chair of Breast Medical Oncology at the University of Texas M.D. Anderson Cancer Center, will report.

The BOLERO-2 findings could shift standard treatment of therapy-resistant patients from sequential use of aromatase inhibitors to simultaneous inhibition of the estrogen-signaling pathway with an aromatase inhibitor such as exemestane and of the PI3-kinase/AKT/mTOR pathway with everolimus.

"For the first time in a large phase III trial, we have demonstrated that this dual-attack is more effective than a single endocrine treatment for patients who have received prior endocrine therapy," Dr. Hortobagyi said in a press statement.

The gain from addition of an mTOR inhibitor comes with a higher incidence of adverse events such as stomatitis, anemia, and dyspnea in patients taking the combination. "In the current study, a high percentage of patients discontinued everolimus because of lack of tolerability," the BOLERO-2 researchers wrote in a report published online Dec. 7 in the New England Journal of Medicine.

"The longer treatment duration in the combination therapy group might have contributed to the high discontinuation rate. Careful monitoring of patients and increased physician awareness of the safety profile of everolimus are warranted," wrote lead author José Baselga, MD, PhD, chief of hematology/oncology and associate director of the Massachusetts General Hospital Cancer Center, and his co-authors.

Between June 2009 and January 2011, Dr. Baselga and his associates at 189 centers in 24 countries randomized 485 women with HR-positive breast cancer refractory to nonsteroidal aromatase inhibitors to receive a combination of everolimus and exemestane (combination therapy group), and 239 women to receive exemestane plus placebo (exemestane-alone group) in the Breast Cancer Trials of Oral Everolimus–2 (BOLERO-2). The mean age of patients was 62 years, 56% had visceral involvement, and 76% had bone metastasis. The primary end point was progression-free survival (N. Engl. J. Med. 2011 Dec. 7 [doi: 10.1056/NEJMoa1109653]).

Dr. Baselga and his associates reported that previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse event was stomatitis (8% in the combination therapy group vs. 1% in the exemestane-alone group), followed by anemia (6% vs. less than 1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. less than 1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%).

"Our positive results are consistent with the outcomes of two other studies of everolimus and antiestrogen therapy in patients with HR-positive breast cancer ... [and] the magnitude of the observed benefit compares favorably with that of the limited options available to this group of patients," the researchers wrote.

Nearly twice as many adverse events were reported among patients in the combination therapy group compared with the exemestane-alone group (23% vs. 12%). Dr. Baselga and his associates observed that "a higher percentage of patients discontinued everolimus in the combination therapy group than discontinued placebo in the control group because of adverse events (19% vs. 4%), and withdrawal of consent (5% vs. 2%). For exemestane discontinuation, the corresponding numbers were 7% versus 3% and 7% versus 2%."

The researchers went on to note that the adverse events seen in the combination therapy group "are consistent with those reported with everolimus and other rapamycin analogues and include stomatitis, fatigue and asthenia, diarrhea, cough, pyrexia, and hyperglycemia."

The study was sponsored by Novartis. Dr. Baselga disclosed that he is a member of the scientific advisory board for Novartis and numerous other companies including Merck and Bayer. He also has accepted consulting fees from numerous pharmaceutical companies. Dr. Hortobagyi reported receiving research funds from and serving as a consultant for Novartis. Some of the other researchers have ties to a variety of pharmaceutical companies.

Combined treatment with everolimus and exemestane more than doubled median progression-free survival in postmenopausal women with hormone receptor–positive breast cancer that had advanced previously after hormone therapy.

Compared with exemestane (Aromasin) and placebo, the everolimus (Afinitor) and exemestane combination increased the median progression-free interval from 3.2 months to 7.4 months, according to Dr. Gabriel N. Hortobagyi, who will present new data from the phase III BOLERO-2 trial at the San Antonio Breast Cancer Symposium.

Moreover, the clinical benefit rate doubled from 25.5% to 50.5%, as twice as many women had either a complete or partial response or stable disease exceeding 6 months, Dr. Hortobagyi, professor and chair of Breast Medical Oncology at the University of Texas M.D. Anderson Cancer Center, will report.

The BOLERO-2 findings could shift standard treatment of therapy-resistant patients from sequential use of aromatase inhibitors to simultaneous inhibition of the estrogen-signaling pathway with an aromatase inhibitor such as exemestane and of the PI3-kinase/AKT/mTOR pathway with everolimus.

"For the first time in a large phase III trial, we have demonstrated that this dual-attack is more effective than a single endocrine treatment for patients who have received prior endocrine therapy," Dr. Hortobagyi said in a press statement.

The gain from addition of an mTOR inhibitor comes with a higher incidence of adverse events such as stomatitis, anemia, and dyspnea in patients taking the combination. "In the current study, a high percentage of patients discontinued everolimus because of lack of tolerability," the BOLERO-2 researchers wrote in a report published online Dec. 7 in the New England Journal of Medicine.

"The longer treatment duration in the combination therapy group might have contributed to the high discontinuation rate. Careful monitoring of patients and increased physician awareness of the safety profile of everolimus are warranted," wrote lead author José Baselga, MD, PhD, chief of hematology/oncology and associate director of the Massachusetts General Hospital Cancer Center, and his co-authors.

Between June 2009 and January 2011, Dr. Baselga and his associates at 189 centers in 24 countries randomized 485 women with HR-positive breast cancer refractory to nonsteroidal aromatase inhibitors to receive a combination of everolimus and exemestane (combination therapy group), and 239 women to receive exemestane plus placebo (exemestane-alone group) in the Breast Cancer Trials of Oral Everolimus–2 (BOLERO-2). The mean age of patients was 62 years, 56% had visceral involvement, and 76% had bone metastasis. The primary end point was progression-free survival (N. Engl. J. Med. 2011 Dec. 7 [doi: 10.1056/NEJMoa1109653]).

Dr. Baselga and his associates reported that previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse event was stomatitis (8% in the combination therapy group vs. 1% in the exemestane-alone group), followed by anemia (6% vs. less than 1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. less than 1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%).

"Our positive results are consistent with the outcomes of two other studies of everolimus and antiestrogen therapy in patients with HR-positive breast cancer ... [and] the magnitude of the observed benefit compares favorably with that of the limited options available to this group of patients," the researchers wrote.

Nearly twice as many adverse events were reported among patients in the combination therapy group compared with the exemestane-alone group (23% vs. 12%). Dr. Baselga and his associates observed that "a higher percentage of patients discontinued everolimus in the combination therapy group than discontinued placebo in the control group because of adverse events (19% vs. 4%), and withdrawal of consent (5% vs. 2%). For exemestane discontinuation, the corresponding numbers were 7% versus 3% and 7% versus 2%."

The researchers went on to note that the adverse events seen in the combination therapy group "are consistent with those reported with everolimus and other rapamycin analogues and include stomatitis, fatigue and asthenia, diarrhea, cough, pyrexia, and hyperglycemia."

The study was sponsored by Novartis. Dr. Baselga disclosed that he is a member of the scientific advisory board for Novartis and numerous other companies including Merck and Bayer. He also has accepted consulting fees from numerous pharmaceutical companies. Dr. Hortobagyi reported receiving research funds from and serving as a consultant for Novartis. Some of the other researchers have ties to a variety of pharmaceutical companies.

SAN ANTONIO – Women may reduce their risk of breast cancer by avoiding unnecessary medical radiation throughout life, avoiding the use of combined estrogen-progestin hormone therapy after menopause, avoiding smoking, limiting alcohol intake, and increasing physical activity level, according to a report by the Institute of Medicine’s Committee on Breast Cancer and the Environment.

The committee was convened in response to a request by Susan G. Komen for the Cure to review evidence on the contribution of environmental exposures to the development of breast cancer. "Environment" was broadly interpreted to include all nongenetic contributors to breast cancer development, from growth patterns to chemical and microbial exposures to social and cultural practices across the lifespan.

The most consistent evidence backs a link between breast cancer and combined hormone therapy, exposure to ionizing radiation, excess weight after menopause, and alcohol consumption. The evidence regarding smoking and breast cancer is less consistent, with some studies showing a causal relationship and others showing limited evidence of a relationship, according to the findings, which were reported during a press briefing held in conjunction with the San Antonio Breast Cancer Symposium.

Evidence is particularly conflicting with regard to physical activity, personal use of hair dyes, and exposure to non-ionizing radiation such as that emitted by microwave ovens and other electrical devices.

Possible associations with even less persuasive evidence include secondhand smoke exposure, nighttime shift work (possibly through disruptions to circadian rhythm), and exposures to benzene, ethylene oxide, and 1,3-butadiene. Exposure to bisphenol A (BPA) presents a "plausible hazard" for which little data exist.

In general, environmental factors found to have any possible link with breast cancer development were associated with less than a doubling of risk.

For an individual woman, the potential risk reduction from avoiding environmental factors would vary, and "may be small or may be moderate," committee chair, Irva Hertz-Picciotto, Ph.D., a professor at the school of medicine at the University of California, Davis, said during the press briefing.

Nonetheless, the impact of risk factor avoidance could be important at a population level, according to the report.

The IOM committee focused on initial breast cancer occurrence, taking into account changes in the breast over a woman’s lifetime, as well as the potential influence of the timing of certain exposures. Diagnosis, treatment, and screening practices were not addressed.

The committee analyzed evidence amassed by the International Agency for Research on Cancer, the World Cancer Research Fund International, and other authoritative organizations. Those data were supplemented by reviews and original research reports from the peer-reviewed literature.

Evidence reviewed primarily focused on exposure during adulthood so the committee was unable to address the effects of various exposures across the life course. Also, many chemical exposures have never been studied in regard to their association with breast cancer.

Furthermore, the contribution of genetic factors and potential gene-environment associations are difficult to assess, the committee conceded.

Topics considered high priority for further research include the role of shift work, endocrine activity, and genotoxicity. Furthermore, research is needed on the "biologic significance of life stages at which environmental risk factors are encountered, what steps may counter their effects, when preventive actions can be most effective, and whether opportunities for prevention can be found for the variety of forms of breast cancer," according to the report.

The report provides a number of strategies for counseling women about how to best prevent breast cancer, according to Dr. Robert Hiatt, a committee member and deputy director of the Comprehensive Cancer Center at the University of California, San Francisco. For example, doctors need to address with their patients the issue of ionizing radiation exposure.

The IOM report was supported by a contract between the National Academy of Sciences and Susan G. Komen for the Cure. Individual authors had no conflicts of interest, according to NAS protocols.

SAN ANTONIO – Women may reduce their risk of breast cancer by avoiding unnecessary medical radiation throughout life, avoiding the use of combined estrogen-progestin hormone therapy after menopause, avoiding smoking, limiting alcohol intake, and increasing physical activity level, according to a report by the Institute of Medicine’s Committee on Breast Cancer and the Environment.

The committee was convened in response to a request by Susan G. Komen for the Cure to review evidence on the contribution of environmental exposures to the development of breast cancer. "Environment" was broadly interpreted to include all nongenetic contributors to breast cancer development, from growth patterns to chemical and microbial exposures to social and cultural practices across the lifespan.

The most consistent evidence backs a link between breast cancer and combined hormone therapy, exposure to ionizing radiation, excess weight after menopause, and alcohol consumption. The evidence regarding smoking and breast cancer is less consistent, with some studies showing a causal relationship and others showing limited evidence of a relationship, according to the findings, which were reported during a press briefing held in conjunction with the San Antonio Breast Cancer Symposium.

Evidence is particularly conflicting with regard to physical activity, personal use of hair dyes, and exposure to non-ionizing radiation such as that emitted by microwave ovens and other electrical devices.

Possible associations with even less persuasive evidence include secondhand smoke exposure, nighttime shift work (possibly through disruptions to circadian rhythm), and exposures to benzene, ethylene oxide, and 1,3-butadiene. Exposure to bisphenol A (BPA) presents a "plausible hazard" for which little data exist.

In general, environmental factors found to have any possible link with breast cancer development were associated with less than a doubling of risk.

For an individual woman, the potential risk reduction from avoiding environmental factors would vary, and "may be small or may be moderate," committee chair, Irva Hertz-Picciotto, Ph.D., a professor at the school of medicine at the University of California, Davis, said during the press briefing.

Nonetheless, the impact of risk factor avoidance could be important at a population level, according to the report.

The IOM committee focused on initial breast cancer occurrence, taking into account changes in the breast over a woman’s lifetime, as well as the potential influence of the timing of certain exposures. Diagnosis, treatment, and screening practices were not addressed.

The committee analyzed evidence amassed by the International Agency for Research on Cancer, the World Cancer Research Fund International, and other authoritative organizations. Those data were supplemented by reviews and original research reports from the peer-reviewed literature.

Evidence reviewed primarily focused on exposure during adulthood so the committee was unable to address the effects of various exposures across the life course. Also, many chemical exposures have never been studied in regard to their association with breast cancer.

Furthermore, the contribution of genetic factors and potential gene-environment associations are difficult to assess, the committee conceded.

Topics considered high priority for further research include the role of shift work, endocrine activity, and genotoxicity. Furthermore, research is needed on the "biologic significance of life stages at which environmental risk factors are encountered, what steps may counter their effects, when preventive actions can be most effective, and whether opportunities for prevention can be found for the variety of forms of breast cancer," according to the report.

The report provides a number of strategies for counseling women about how to best prevent breast cancer, according to Dr. Robert Hiatt, a committee member and deputy director of the Comprehensive Cancer Center at the University of California, San Francisco. For example, doctors need to address with their patients the issue of ionizing radiation exposure.

The IOM report was supported by a contract between the National Academy of Sciences and Susan G. Komen for the Cure. Individual authors had no conflicts of interest, according to NAS protocols.

SAN ANTONIO – Women may reduce their risk of breast cancer by avoiding unnecessary medical radiation throughout life, avoiding the use of combined estrogen-progestin hormone therapy after menopause, avoiding smoking, limiting alcohol intake, and increasing physical activity level, according to a report by the Institute of Medicine’s Committee on Breast Cancer and the Environment.

The committee was convened in response to a request by Susan G. Komen for the Cure to review evidence on the contribution of environmental exposures to the development of breast cancer. "Environment" was broadly interpreted to include all nongenetic contributors to breast cancer development, from growth patterns to chemical and microbial exposures to social and cultural practices across the lifespan.

The most consistent evidence backs a link between breast cancer and combined hormone therapy, exposure to ionizing radiation, excess weight after menopause, and alcohol consumption. The evidence regarding smoking and breast cancer is less consistent, with some studies showing a causal relationship and others showing limited evidence of a relationship, according to the findings, which were reported during a press briefing held in conjunction with the San Antonio Breast Cancer Symposium.

Evidence is particularly conflicting with regard to physical activity, personal use of hair dyes, and exposure to non-ionizing radiation such as that emitted by microwave ovens and other electrical devices.

Possible associations with even less persuasive evidence include secondhand smoke exposure, nighttime shift work (possibly through disruptions to circadian rhythm), and exposures to benzene, ethylene oxide, and 1,3-butadiene. Exposure to bisphenol A (BPA) presents a "plausible hazard" for which little data exist.

In general, environmental factors found to have any possible link with breast cancer development were associated with less than a doubling of risk.

For an individual woman, the potential risk reduction from avoiding environmental factors would vary, and "may be small or may be moderate," committee chair, Irva Hertz-Picciotto, Ph.D., a professor at the school of medicine at the University of California, Davis, said during the press briefing.

Nonetheless, the impact of risk factor avoidance could be important at a population level, according to the report.

The IOM committee focused on initial breast cancer occurrence, taking into account changes in the breast over a woman’s lifetime, as well as the potential influence of the timing of certain exposures. Diagnosis, treatment, and screening practices were not addressed.

The committee analyzed evidence amassed by the International Agency for Research on Cancer, the World Cancer Research Fund International, and other authoritative organizations. Those data were supplemented by reviews and original research reports from the peer-reviewed literature.

Evidence reviewed primarily focused on exposure during adulthood so the committee was unable to address the effects of various exposures across the life course. Also, many chemical exposures have never been studied in regard to their association with breast cancer.

Furthermore, the contribution of genetic factors and potential gene-environment associations are difficult to assess, the committee conceded.

Topics considered high priority for further research include the role of shift work, endocrine activity, and genotoxicity. Furthermore, research is needed on the "biologic significance of life stages at which environmental risk factors are encountered, what steps may counter their effects, when preventive actions can be most effective, and whether opportunities for prevention can be found for the variety of forms of breast cancer," according to the report.

The report provides a number of strategies for counseling women about how to best prevent breast cancer, according to Dr. Robert Hiatt, a committee member and deputy director of the Comprehensive Cancer Center at the University of California, San Francisco. For example, doctors need to address with their patients the issue of ionizing radiation exposure.

The IOM report was supported by a contract between the National Academy of Sciences and Susan G. Komen for the Cure. Individual authors had no conflicts of interest, according to NAS protocols.

SAN ANTONIO – Adding zoledronic acid to adjuvant endocrine therapy significantly improves disease-free and overall survival in premenopausal women with endocrine-receptor–positive early breast cancer at 7 years’ follow-up, Dr. Michael Gnant reported today at the San Antonio Breast Cancer Symposium.

Women in the ABCSG (Austrian Breast and Colorectal Cancer Study Group)-12 trial randomized to receive zoledronic acid in addition to ovarian function suppression and endocrine therapy had a 28% reduction in risk of recurrence and 37% reduction in mortality risk at 84 months, compared with women randomized to adjuvant endocrine therapy alone, according to Dr. Gnant, professor of surgery at the Medical University of Vienna.

The findings confirm data previously reported by the ABCSG-12 investigators demonstrating disease-free and overall survival benefits associated with the treatment regimen at 48 and 62 months of follow up (Lancet Oncol. 2011;12:631-41). "The continued success of this treatment means we can intervene early and still observe persistence of the benefit of treatment," said Dr. Gnant, president of the ABSCG.

The four-arm open-label trial randomly assigned 1,803 women to ovarian suppression and endocrine therapy plus or minus zoledronic acid for 3 years. Investigators used log-rank tests and Cox models to evaluate disease-free survival and overall survival, Dr. Gnant explained.

All of the patients, mean age 44.5 years, were premenopausal and had undergone surgery for stage I or II hormone receptor–positive breast cancer. They were treated for 3 years with 3.6 mg subcutaneous goserelin every 28 days, and randomized to 20 mg of oral tamoxifen daily plus placebo, 1 mg of oral anastrozole daily plus placebo, or either of the latter with 4 mg intravenous zoledronic acid every 6 months.

At a median 84 months’ follow-up, the hazard ratios for breast cancer recurrence and death, respectively, for women receiving adjuvant zoledronic acid were .72 and .63, Dr. Gnant reported, noting that the reductions remained significant in univariate and multivariate analyses. Further, in multivariate analysis, "there was no interaction between zoledronic acid and tumor parameters or endocrine therapy," he said. "The hazard ratios were identical for small and large tumors, node-positive and node-negative tumors, and for patients receiving anastrozole and tamoxifen."

There was a strong interaction between zoledronic acid and age in terms of survival benefit, however, with patients older than 40 years experiencing a 34% reduction in recurrence risk and a 44% reduction in mortality, according to Dr. Gnant. No similarly significant survival benefits were observed among patients younger than 40 years, he said.

As expected, patients receiving zoledronic acid experienced more arthralgia, Dr. Gnant stated, "but, importantly, there were no cases of osteonecrosis of the jaw and no renal failure in the treatment population."

The findings, which are consistent with those seen in the postmenopausal cohort of the AZURE trial, "suggest that estrogen deprivation and reduction of bone turnover-derived growth factors in the bone marrow microenvironment are needed to sufficiently suppress dormant micrometastases," Dr. Gnant explained. Together with the known bone-protective benefits of zoledronic acid, the new data provide sufficient support for adding the bisphosphonate to adjuvant endocrine therapy in premenopausal women with early endocrine-receptor–positive breast cancer, he said.

Dr. James N. Ingle of the Mayo Clinic in Rochester, Minn., the discussant for the session, concluded that the ABCSG-12 findings provide level-one evidence for the value of adding zoledronic acid to goserelin and tamoxifen or anastrozole in this patient population. "Zoledronic acid as standard of care [in these patients] will be more widely accepted when the results of the ongoing SOFT [Suppression of Ovarian Function trial] are reported," which will clarify the value of tamoxifen vs. exemestane (Aromasin) in conjunction with ovarian suppression, he said.

Dr. Gnant and Dr. Ingle reported having no relevant financial disclosures.

SAN ANTONIO – Adding zoledronic acid to adjuvant endocrine therapy significantly improves disease-free and overall survival in premenopausal women with endocrine-receptor–positive early breast cancer at 7 years’ follow-up, Dr. Michael Gnant reported today at the San Antonio Breast Cancer Symposium.

Women in the ABCSG (Austrian Breast and Colorectal Cancer Study Group)-12 trial randomized to receive zoledronic acid in addition to ovarian function suppression and endocrine therapy had a 28% reduction in risk of recurrence and 37% reduction in mortality risk at 84 months, compared with women randomized to adjuvant endocrine therapy alone, according to Dr. Gnant, professor of surgery at the Medical University of Vienna.

The findings confirm data previously reported by the ABCSG-12 investigators demonstrating disease-free and overall survival benefits associated with the treatment regimen at 48 and 62 months of follow up (Lancet Oncol. 2011;12:631-41). "The continued success of this treatment means we can intervene early and still observe persistence of the benefit of treatment," said Dr. Gnant, president of the ABSCG.

The four-arm open-label trial randomly assigned 1,803 women to ovarian suppression and endocrine therapy plus or minus zoledronic acid for 3 years. Investigators used log-rank tests and Cox models to evaluate disease-free survival and overall survival, Dr. Gnant explained.

All of the patients, mean age 44.5 years, were premenopausal and had undergone surgery for stage I or II hormone receptor–positive breast cancer. They were treated for 3 years with 3.6 mg subcutaneous goserelin every 28 days, and randomized to 20 mg of oral tamoxifen daily plus placebo, 1 mg of oral anastrozole daily plus placebo, or either of the latter with 4 mg intravenous zoledronic acid every 6 months.

At a median 84 months’ follow-up, the hazard ratios for breast cancer recurrence and death, respectively, for women receiving adjuvant zoledronic acid were .72 and .63, Dr. Gnant reported, noting that the reductions remained significant in univariate and multivariate analyses. Further, in multivariate analysis, "there was no interaction between zoledronic acid and tumor parameters or endocrine therapy," he said. "The hazard ratios were identical for small and large tumors, node-positive and node-negative tumors, and for patients receiving anastrozole and tamoxifen."

There was a strong interaction between zoledronic acid and age in terms of survival benefit, however, with patients older than 40 years experiencing a 34% reduction in recurrence risk and a 44% reduction in mortality, according to Dr. Gnant. No similarly significant survival benefits were observed among patients younger than 40 years, he said.

As expected, patients receiving zoledronic acid experienced more arthralgia, Dr. Gnant stated, "but, importantly, there were no cases of osteonecrosis of the jaw and no renal failure in the treatment population."

The findings, which are consistent with those seen in the postmenopausal cohort of the AZURE trial, "suggest that estrogen deprivation and reduction of bone turnover-derived growth factors in the bone marrow microenvironment are needed to sufficiently suppress dormant micrometastases," Dr. Gnant explained. Together with the known bone-protective benefits of zoledronic acid, the new data provide sufficient support for adding the bisphosphonate to adjuvant endocrine therapy in premenopausal women with early endocrine-receptor–positive breast cancer, he said.

Dr. James N. Ingle of the Mayo Clinic in Rochester, Minn., the discussant for the session, concluded that the ABCSG-12 findings provide level-one evidence for the value of adding zoledronic acid to goserelin and tamoxifen or anastrozole in this patient population. "Zoledronic acid as standard of care [in these patients] will be more widely accepted when the results of the ongoing SOFT [Suppression of Ovarian Function trial] are reported," which will clarify the value of tamoxifen vs. exemestane (Aromasin) in conjunction with ovarian suppression, he said.

Dr. Gnant and Dr. Ingle reported having no relevant financial disclosures.

SAN ANTONIO – Adding zoledronic acid to adjuvant endocrine therapy significantly improves disease-free and overall survival in premenopausal women with endocrine-receptor–positive early breast cancer at 7 years’ follow-up, Dr. Michael Gnant reported today at the San Antonio Breast Cancer Symposium.

Women in the ABCSG (Austrian Breast and Colorectal Cancer Study Group)-12 trial randomized to receive zoledronic acid in addition to ovarian function suppression and endocrine therapy had a 28% reduction in risk of recurrence and 37% reduction in mortality risk at 84 months, compared with women randomized to adjuvant endocrine therapy alone, according to Dr. Gnant, professor of surgery at the Medical University of Vienna.

The findings confirm data previously reported by the ABCSG-12 investigators demonstrating disease-free and overall survival benefits associated with the treatment regimen at 48 and 62 months of follow up (Lancet Oncol. 2011;12:631-41). "The continued success of this treatment means we can intervene early and still observe persistence of the benefit of treatment," said Dr. Gnant, president of the ABSCG.

The four-arm open-label trial randomly assigned 1,803 women to ovarian suppression and endocrine therapy plus or minus zoledronic acid for 3 years. Investigators used log-rank tests and Cox models to evaluate disease-free survival and overall survival, Dr. Gnant explained.

All of the patients, mean age 44.5 years, were premenopausal and had undergone surgery for stage I or II hormone receptor–positive breast cancer. They were treated for 3 years with 3.6 mg subcutaneous goserelin every 28 days, and randomized to 20 mg of oral tamoxifen daily plus placebo, 1 mg of oral anastrozole daily plus placebo, or either of the latter with 4 mg intravenous zoledronic acid every 6 months.

At a median 84 months’ follow-up, the hazard ratios for breast cancer recurrence and death, respectively, for women receiving adjuvant zoledronic acid were .72 and .63, Dr. Gnant reported, noting that the reductions remained significant in univariate and multivariate analyses. Further, in multivariate analysis, "there was no interaction between zoledronic acid and tumor parameters or endocrine therapy," he said. "The hazard ratios were identical for small and large tumors, node-positive and node-negative tumors, and for patients receiving anastrozole and tamoxifen."

There was a strong interaction between zoledronic acid and age in terms of survival benefit, however, with patients older than 40 years experiencing a 34% reduction in recurrence risk and a 44% reduction in mortality, according to Dr. Gnant. No similarly significant survival benefits were observed among patients younger than 40 years, he said.

As expected, patients receiving zoledronic acid experienced more arthralgia, Dr. Gnant stated, "but, importantly, there were no cases of osteonecrosis of the jaw and no renal failure in the treatment population."

The findings, which are consistent with those seen in the postmenopausal cohort of the AZURE trial, "suggest that estrogen deprivation and reduction of bone turnover-derived growth factors in the bone marrow microenvironment are needed to sufficiently suppress dormant micrometastases," Dr. Gnant explained. Together with the known bone-protective benefits of zoledronic acid, the new data provide sufficient support for adding the bisphosphonate to adjuvant endocrine therapy in premenopausal women with early endocrine-receptor–positive breast cancer, he said.

Dr. James N. Ingle of the Mayo Clinic in Rochester, Minn., the discussant for the session, concluded that the ABCSG-12 findings provide level-one evidence for the value of adding zoledronic acid to goserelin and tamoxifen or anastrozole in this patient population. "Zoledronic acid as standard of care [in these patients] will be more widely accepted when the results of the ongoing SOFT [Suppression of Ovarian Function trial] are reported," which will clarify the value of tamoxifen vs. exemestane (Aromasin) in conjunction with ovarian suppression, he said.

Dr. Gnant and Dr. Ingle reported having no relevant financial disclosures.

SAN ANTONIO – An investigational genetic test may not only be able to differentiate women likely to have early recurrence of estrogen receptor–positive breast cancer but also could lead to novel combinations of existing drugs to treat these patients earlier in the disease process, according to Dr. Minetta C. Liu.

Researchers developed a 91-gene classifier "that essentially separated those patients who were going to recur early [within 3 years] vs. those who were going to recur late [beyond 10 years]," Dr. Liu announced at a press briefing held during the San Antonio Breast Cancer Symposium.

"Our work is very much hypothesis generating. To be able to identify early vs. late recurrences at the time of diagnosis would be useful, but we actually need to be able to know what to do about it once we identify it," said Dr. Liu, director of translational breast cancer research at Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C.

The ability to reliably predict early treatment failure may help to identify patients who require agents beyond endocrine therapy to prevent the early onset of distant metastases, she said. "We hope to exploit these molecular differences of early vs. later recurrences to help us guide novel drug combinations in ER–positive early-stage disease," Dr. Liu added.

Session moderator Dr. Jennifer A. Ligibel of Dana-Farber Cancer Institute, Boston, agreed: This type of analysis "will help us to give chemotherapy to fewer patients potentially, if they do not have tumors that are consistent with early relapse and to know which patients really require extended therapy beyond the initial 5 years of treatment of endocrine therapy for patients who are potentially destined for late relapse."

The researchers acquired snap-frozen, pretreatment tumor biopsies collected at the Edinburgh Breakthrough Research Unit in Scotland between 1982 and 1990. The samples were from patients with stages I-III estrogen receptor–positive breast cancer, starting tamoxifen-alone adjuvant treatment. These patients had to have at least a 10-year follow-up in the absence of distant release.

A histology review was performed of the samples and those that contained at least 50% tumor were cleared for RNA extraction for gene expression profiling.

This training data set included 111 samples, with 57 relapses. Tumors from patients with relapse were subdivided into early recurrence (within 3 years of diagnosis) and late recurrence (more than 10 years). A total of 25 patients had early recurrences and 22 had late recurrences. Median follow-up was 13 years.

The investigators selected a validation data set from the literature that met certain criteria, such as quality of data and follow-up (BMC Genomics 2008;9:239). This previously published data set included 255 samples from patients with stages I-II estrogen receptor–positive breast cancer with tamoxifen-alone adjuvant treatment. Of these, 67 had distant relapse – 25 patients had early recurrences and 7 had late recurrences. The median follow-up was 9 years.

Using this training data set, the researchers developed a 91-gene classifier "that essentially separated those patients, who were going to recur early vs. those who were going to recur late," Dr. Liu said. They optimized the classifier and applied it to a validation data set.

"We had very high accuracy, sensitivity, specificity, positive predictive value, and negative predictive value," said Dr. Liu. However, "we didn’t stop at developing a classifier. We wanted to understand what these genes are trying to tell us within the classifier. ... A novel computational method allowed us to look at [estrogen receptor]network topology – to create a map basically."

The investigators identified several genes that were overexpressed in patients with early recurrences: CALM1, CALM2, CALM3, SRC, CDK1, and MAPK1. They also identified genes that had increased expression in patients with late recurrences: ESR1, ESR2, EGFR, BCL2, and AR.

"Clearly there are robust molecular differences between those tumors that recur early versus those that recur much later despite adjuvant tamoxifen. The majority of the genes in our classifier relate to apoptosis and proliferation," said Dr. Liu.

"I want to emphasize that we’re not just about developing a score and identifying these patients. We actually want to do something about it and understand what the underlying mechanisms are behind these genetic differences."

Dr. Liu reported that she has no relevant financial disclosures.

SAN ANTONIO – An investigational genetic test may not only be able to differentiate women likely to have early recurrence of estrogen receptor–positive breast cancer but also could lead to novel combinations of existing drugs to treat these patients earlier in the disease process, according to Dr. Minetta C. Liu.

Researchers developed a 91-gene classifier "that essentially separated those patients who were going to recur early [within 3 years] vs. those who were going to recur late [beyond 10 years]," Dr. Liu announced at a press briefing held during the San Antonio Breast Cancer Symposium.

"Our work is very much hypothesis generating. To be able to identify early vs. late recurrences at the time of diagnosis would be useful, but we actually need to be able to know what to do about it once we identify it," said Dr. Liu, director of translational breast cancer research at Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C.

The ability to reliably predict early treatment failure may help to identify patients who require agents beyond endocrine therapy to prevent the early onset of distant metastases, she said. "We hope to exploit these molecular differences of early vs. later recurrences to help us guide novel drug combinations in ER–positive early-stage disease," Dr. Liu added.

Session moderator Dr. Jennifer A. Ligibel of Dana-Farber Cancer Institute, Boston, agreed: This type of analysis "will help us to give chemotherapy to fewer patients potentially, if they do not have tumors that are consistent with early relapse and to know which patients really require extended therapy beyond the initial 5 years of treatment of endocrine therapy for patients who are potentially destined for late relapse."

The researchers acquired snap-frozen, pretreatment tumor biopsies collected at the Edinburgh Breakthrough Research Unit in Scotland between 1982 and 1990. The samples were from patients with stages I-III estrogen receptor–positive breast cancer, starting tamoxifen-alone adjuvant treatment. These patients had to have at least a 10-year follow-up in the absence of distant release.

A histology review was performed of the samples and those that contained at least 50% tumor were cleared for RNA extraction for gene expression profiling.

This training data set included 111 samples, with 57 relapses. Tumors from patients with relapse were subdivided into early recurrence (within 3 years of diagnosis) and late recurrence (more than 10 years). A total of 25 patients had early recurrences and 22 had late recurrences. Median follow-up was 13 years.

The investigators selected a validation data set from the literature that met certain criteria, such as quality of data and follow-up (BMC Genomics 2008;9:239). This previously published data set included 255 samples from patients with stages I-II estrogen receptor–positive breast cancer with tamoxifen-alone adjuvant treatment. Of these, 67 had distant relapse – 25 patients had early recurrences and 7 had late recurrences. The median follow-up was 9 years.

Using this training data set, the researchers developed a 91-gene classifier "that essentially separated those patients, who were going to recur early vs. those who were going to recur late," Dr. Liu said. They optimized the classifier and applied it to a validation data set.

"We had very high accuracy, sensitivity, specificity, positive predictive value, and negative predictive value," said Dr. Liu. However, "we didn’t stop at developing a classifier. We wanted to understand what these genes are trying to tell us within the classifier. ... A novel computational method allowed us to look at [estrogen receptor]network topology – to create a map basically."

The investigators identified several genes that were overexpressed in patients with early recurrences: CALM1, CALM2, CALM3, SRC, CDK1, and MAPK1. They also identified genes that had increased expression in patients with late recurrences: ESR1, ESR2, EGFR, BCL2, and AR.

"Clearly there are robust molecular differences between those tumors that recur early versus those that recur much later despite adjuvant tamoxifen. The majority of the genes in our classifier relate to apoptosis and proliferation," said Dr. Liu.

"I want to emphasize that we’re not just about developing a score and identifying these patients. We actually want to do something about it and understand what the underlying mechanisms are behind these genetic differences."

Dr. Liu reported that she has no relevant financial disclosures.

SAN ANTONIO – An investigational genetic test may not only be able to differentiate women likely to have early recurrence of estrogen receptor–positive breast cancer but also could lead to novel combinations of existing drugs to treat these patients earlier in the disease process, according to Dr. Minetta C. Liu.

Researchers developed a 91-gene classifier "that essentially separated those patients who were going to recur early [within 3 years] vs. those who were going to recur late [beyond 10 years]," Dr. Liu announced at a press briefing held during the San Antonio Breast Cancer Symposium.

"Our work is very much hypothesis generating. To be able to identify early vs. late recurrences at the time of diagnosis would be useful, but we actually need to be able to know what to do about it once we identify it," said Dr. Liu, director of translational breast cancer research at Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C.

The ability to reliably predict early treatment failure may help to identify patients who require agents beyond endocrine therapy to prevent the early onset of distant metastases, she said. "We hope to exploit these molecular differences of early vs. later recurrences to help us guide novel drug combinations in ER–positive early-stage disease," Dr. Liu added.

Session moderator Dr. Jennifer A. Ligibel of Dana-Farber Cancer Institute, Boston, agreed: This type of analysis "will help us to give chemotherapy to fewer patients potentially, if they do not have tumors that are consistent with early relapse and to know which patients really require extended therapy beyond the initial 5 years of treatment of endocrine therapy for patients who are potentially destined for late relapse."

The researchers acquired snap-frozen, pretreatment tumor biopsies collected at the Edinburgh Breakthrough Research Unit in Scotland between 1982 and 1990. The samples were from patients with stages I-III estrogen receptor–positive breast cancer, starting tamoxifen-alone adjuvant treatment. These patients had to have at least a 10-year follow-up in the absence of distant release.

A histology review was performed of the samples and those that contained at least 50% tumor were cleared for RNA extraction for gene expression profiling.

This training data set included 111 samples, with 57 relapses. Tumors from patients with relapse were subdivided into early recurrence (within 3 years of diagnosis) and late recurrence (more than 10 years). A total of 25 patients had early recurrences and 22 had late recurrences. Median follow-up was 13 years.

The investigators selected a validation data set from the literature that met certain criteria, such as quality of data and follow-up (BMC Genomics 2008;9:239). This previously published data set included 255 samples from patients with stages I-II estrogen receptor–positive breast cancer with tamoxifen-alone adjuvant treatment. Of these, 67 had distant relapse – 25 patients had early recurrences and 7 had late recurrences. The median follow-up was 9 years.

Using this training data set, the researchers developed a 91-gene classifier "that essentially separated those patients, who were going to recur early vs. those who were going to recur late," Dr. Liu said. They optimized the classifier and applied it to a validation data set.

"We had very high accuracy, sensitivity, specificity, positive predictive value, and negative predictive value," said Dr. Liu. However, "we didn’t stop at developing a classifier. We wanted to understand what these genes are trying to tell us within the classifier. ... A novel computational method allowed us to look at [estrogen receptor]network topology – to create a map basically."

The investigators identified several genes that were overexpressed in patients with early recurrences: CALM1, CALM2, CALM3, SRC, CDK1, and MAPK1. They also identified genes that had increased expression in patients with late recurrences: ESR1, ESR2, EGFR, BCL2, and AR.

"Clearly there are robust molecular differences between those tumors that recur early versus those that recur much later despite adjuvant tamoxifen. The majority of the genes in our classifier relate to apoptosis and proliferation," said Dr. Liu.

"I want to emphasize that we’re not just about developing a score and identifying these patients. We actually want to do something about it and understand what the underlying mechanisms are behind these genetic differences."

Dr. Liu reported that she has no relevant financial disclosures.

SAN ANTONIO – Accelerated partial-breast brachytherapy, delivered as part of breast-conserving therapy for early breast cancer, was associated with twice the mastectomy rate when compared with standard whole-breast irradiation in a large study.

Moreover, accelerated partial-breast brachytherapy entailed substantially higher rates of both acute and late complications, Dr. Benjamin D. Smith said in a presentation of the study findings at the San Antonio Breast Cancer Symposium.

Investigators reviewed Medicare claims data for all 130,535 beneficiaries whose early breast cancer was treated with lumpectomy followed by adjuvant radiation during 2000-2007. The use of accelerated partial-breast brachytherapy in this population rose from less than 1% in 2000 to 13% in 2007.

The incidence of mastectomy during 5 years of follow-up was 4% in 7,291 brachytherapy recipients, compared with 2% after whole breast irradiation (P less than .001). Upon adjustment for the brachytherapy recipients’ older average age, more comorbid conditions, and lesser rate of positive axillary lymph nodes, brachytherapy was associated with a 2.2-fold increased risk of losing the treated breast within 5 years, reported Dr. Smith, a radiation oncologist at the University of Texas M.D. Anderson Cancer Center, Houston.

"When we adjusted for various clinical and sociodemographic factors, to our surprise brachytherapy was the variable that had the strongest correlation with the risk of subsequent mastectomy," he noted.

Partial-breast brachytherapy was also associated with significantly higher rates of postoperative wound infection and acute noninfectious complications as well as increased 5-year rates of fat necrosis and breast pain. Fat necrosis is considered a marker of tissue injury caused by surgery and/or radiotherapy.

Within 1 year of breast cancer diagnosis, infectious complications involving breast or surrounding skin or soft tissues occurred in 16% of women treated with brachytherapy vs. 10% of those who received standard whole breast radiation.

Noninfectious complications including surgical wound breakdown, postoperative bleeding, or seroma formation were twice as common with brachytherapy at 16% and 8%, respectively.

Five-year rates of fat necrosis (9% vs. 4%) and breast pain (15% vs. 12%) also were higher with brachytherapy.

Accelerated partial-breast brachytherapy was developed to address the shortcomings of whole-breast irradiation, the historic standard of care, which entails up to 7 weeks of daily Monday-through-Friday treatment. Whole-breast irradiation is inconvenient. Indeed, it’s such a hardship, especially for patients in rural areas distant from a radiotherapy center, that some women opt for mastectomy as a matter of convenience. Moreover, 15%-30% of women who undergo lumpectomy forgo prescribed radiation therapy, placing themselves at increased risk of local recurrence.

Accelerated partial-breast brachytherapy may improve patient compliance with radiotherapy. It shortens the treatment course to 1 week. It entails temporary placement of radioactive beads within the breast via a catheter system. This method delivers radiation only to breast tissue immediately adjacent to the lumpectomy. This technique is but one of several forms of partial breast irradiation, however; the new findings don’t apply to 3-D external beam radiation, for example.

Accelerated partial breast brachytherapy has boomed in popularity in recent years, especially in community practice. But these new data may put the brakes on that trend.

"This study has changed the way that I think about these two different treatment options, and it’s changed the way I practice," Dr. Smith said in an interview.

Dr. Jennifer A. Ligibel, who chaired a press conference where Dr. Smith presented his findings, said the study carries an important message: "Although observational data using a claims database are no substitute for a randomized trial with long-term follow-up, what we see in this study is that this technique was not as effective and it was also associated with a lot more complications. So if your argument in using this is that it’s sparing patients from additional problems, we’re not seeing that in this study.

"I think this study really does give pause to the incorporation of accelerated partial-breast brachytherapy into routine clinical practice. These results should make people wait for the results of the ongoing randomized trials before they offer this as a standard procedure for their patients," added Dr. Ligibel of Dana-Farber Cancer Center, Boston.

The major randomized trial underway is the National Surgical Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 study. The NSABP B-39/RTOG 0413 trial has enrolled 4,000 of a planned 4,500 patients with early breast cancer. The emphasis is on patients under age 50, since they have a higher local recurrence risk than older women. Participants are randomized to whole-breast radiation or various forms of partial breast irradiation after lumpectomy. Mature results aren’t expected until mid-decade.

Dr. Smith and Dr. Ligibel declared having no relevant financial interests.

SAN ANTONIO – Accelerated partial-breast brachytherapy, delivered as part of breast-conserving therapy for early breast cancer, was associated with twice the mastectomy rate when compared with standard whole-breast irradiation in a large study.

Moreover, accelerated partial-breast brachytherapy entailed substantially higher rates of both acute and late complications, Dr. Benjamin D. Smith said in a presentation of the study findings at the San Antonio Breast Cancer Symposium.

Investigators reviewed Medicare claims data for all 130,535 beneficiaries whose early breast cancer was treated with lumpectomy followed by adjuvant radiation during 2000-2007. The use of accelerated partial-breast brachytherapy in this population rose from less than 1% in 2000 to 13% in 2007.

The incidence of mastectomy during 5 years of follow-up was 4% in 7,291 brachytherapy recipients, compared with 2% after whole breast irradiation (P less than .001). Upon adjustment for the brachytherapy recipients’ older average age, more comorbid conditions, and lesser rate of positive axillary lymph nodes, brachytherapy was associated with a 2.2-fold increased risk of losing the treated breast within 5 years, reported Dr. Smith, a radiation oncologist at the University of Texas M.D. Anderson Cancer Center, Houston.

"When we adjusted for various clinical and sociodemographic factors, to our surprise brachytherapy was the variable that had the strongest correlation with the risk of subsequent mastectomy," he noted.

Partial-breast brachytherapy was also associated with significantly higher rates of postoperative wound infection and acute noninfectious complications as well as increased 5-year rates of fat necrosis and breast pain. Fat necrosis is considered a marker of tissue injury caused by surgery and/or radiotherapy.

Within 1 year of breast cancer diagnosis, infectious complications involving breast or surrounding skin or soft tissues occurred in 16% of women treated with brachytherapy vs. 10% of those who received standard whole breast radiation.

Noninfectious complications including surgical wound breakdown, postoperative bleeding, or seroma formation were twice as common with brachytherapy at 16% and 8%, respectively.

Five-year rates of fat necrosis (9% vs. 4%) and breast pain (15% vs. 12%) also were higher with brachytherapy.

Accelerated partial-breast brachytherapy was developed to address the shortcomings of whole-breast irradiation, the historic standard of care, which entails up to 7 weeks of daily Monday-through-Friday treatment. Whole-breast irradiation is inconvenient. Indeed, it’s such a hardship, especially for patients in rural areas distant from a radiotherapy center, that some women opt for mastectomy as a matter of convenience. Moreover, 15%-30% of women who undergo lumpectomy forgo prescribed radiation therapy, placing themselves at increased risk of local recurrence.

Accelerated partial-breast brachytherapy may improve patient compliance with radiotherapy. It shortens the treatment course to 1 week. It entails temporary placement of radioactive beads within the breast via a catheter system. This method delivers radiation only to breast tissue immediately adjacent to the lumpectomy. This technique is but one of several forms of partial breast irradiation, however; the new findings don’t apply to 3-D external beam radiation, for example.

Accelerated partial breast brachytherapy has boomed in popularity in recent years, especially in community practice. But these new data may put the brakes on that trend.

"This study has changed the way that I think about these two different treatment options, and it’s changed the way I practice," Dr. Smith said in an interview.

Dr. Jennifer A. Ligibel, who chaired a press conference where Dr. Smith presented his findings, said the study carries an important message: "Although observational data using a claims database are no substitute for a randomized trial with long-term follow-up, what we see in this study is that this technique was not as effective and it was also associated with a lot more complications. So if your argument in using this is that it’s sparing patients from additional problems, we’re not seeing that in this study.

"I think this study really does give pause to the incorporation of accelerated partial-breast brachytherapy into routine clinical practice. These results should make people wait for the results of the ongoing randomized trials before they offer this as a standard procedure for their patients," added Dr. Ligibel of Dana-Farber Cancer Center, Boston.

The major randomized trial underway is the National Surgical Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 study. The NSABP B-39/RTOG 0413 trial has enrolled 4,000 of a planned 4,500 patients with early breast cancer. The emphasis is on patients under age 50, since they have a higher local recurrence risk than older women. Participants are randomized to whole-breast radiation or various forms of partial breast irradiation after lumpectomy. Mature results aren’t expected until mid-decade.

Dr. Smith and Dr. Ligibel declared having no relevant financial interests.

SAN ANTONIO – Accelerated partial-breast brachytherapy, delivered as part of breast-conserving therapy for early breast cancer, was associated with twice the mastectomy rate when compared with standard whole-breast irradiation in a large study.

Moreover, accelerated partial-breast brachytherapy entailed substantially higher rates of both acute and late complications, Dr. Benjamin D. Smith said in a presentation of the study findings at the San Antonio Breast Cancer Symposium.

Investigators reviewed Medicare claims data for all 130,535 beneficiaries whose early breast cancer was treated with lumpectomy followed by adjuvant radiation during 2000-2007. The use of accelerated partial-breast brachytherapy in this population rose from less than 1% in 2000 to 13% in 2007.

The incidence of mastectomy during 5 years of follow-up was 4% in 7,291 brachytherapy recipients, compared with 2% after whole breast irradiation (P less than .001). Upon adjustment for the brachytherapy recipients’ older average age, more comorbid conditions, and lesser rate of positive axillary lymph nodes, brachytherapy was associated with a 2.2-fold increased risk of losing the treated breast within 5 years, reported Dr. Smith, a radiation oncologist at the University of Texas M.D. Anderson Cancer Center, Houston.

"When we adjusted for various clinical and sociodemographic factors, to our surprise brachytherapy was the variable that had the strongest correlation with the risk of subsequent mastectomy," he noted.

Partial-breast brachytherapy was also associated with significantly higher rates of postoperative wound infection and acute noninfectious complications as well as increased 5-year rates of fat necrosis and breast pain. Fat necrosis is considered a marker of tissue injury caused by surgery and/or radiotherapy.

Within 1 year of breast cancer diagnosis, infectious complications involving breast or surrounding skin or soft tissues occurred in 16% of women treated with brachytherapy vs. 10% of those who received standard whole breast radiation.

Noninfectious complications including surgical wound breakdown, postoperative bleeding, or seroma formation were twice as common with brachytherapy at 16% and 8%, respectively.

Five-year rates of fat necrosis (9% vs. 4%) and breast pain (15% vs. 12%) also were higher with brachytherapy.

Accelerated partial-breast brachytherapy was developed to address the shortcomings of whole-breast irradiation, the historic standard of care, which entails up to 7 weeks of daily Monday-through-Friday treatment. Whole-breast irradiation is inconvenient. Indeed, it’s such a hardship, especially for patients in rural areas distant from a radiotherapy center, that some women opt for mastectomy as a matter of convenience. Moreover, 15%-30% of women who undergo lumpectomy forgo prescribed radiation therapy, placing themselves at increased risk of local recurrence.

Accelerated partial-breast brachytherapy may improve patient compliance with radiotherapy. It shortens the treatment course to 1 week. It entails temporary placement of radioactive beads within the breast via a catheter system. This method delivers radiation only to breast tissue immediately adjacent to the lumpectomy. This technique is but one of several forms of partial breast irradiation, however; the new findings don’t apply to 3-D external beam radiation, for example.

Accelerated partial breast brachytherapy has boomed in popularity in recent years, especially in community practice. But these new data may put the brakes on that trend.

"This study has changed the way that I think about these two different treatment options, and it’s changed the way I practice," Dr. Smith said in an interview.

Dr. Jennifer A. Ligibel, who chaired a press conference where Dr. Smith presented his findings, said the study carries an important message: "Although observational data using a claims database are no substitute for a randomized trial with long-term follow-up, what we see in this study is that this technique was not as effective and it was also associated with a lot more complications. So if your argument in using this is that it’s sparing patients from additional problems, we’re not seeing that in this study.

"I think this study really does give pause to the incorporation of accelerated partial-breast brachytherapy into routine clinical practice. These results should make people wait for the results of the ongoing randomized trials before they offer this as a standard procedure for their patients," added Dr. Ligibel of Dana-Farber Cancer Center, Boston.

The major randomized trial underway is the National Surgical Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 study. The NSABP B-39/RTOG 0413 trial has enrolled 4,000 of a planned 4,500 patients with early breast cancer. The emphasis is on patients under age 50, since they have a higher local recurrence risk than older women. Participants are randomized to whole-breast radiation or various forms of partial breast irradiation after lumpectomy. Mature results aren’t expected until mid-decade.

Dr. Smith and Dr. Ligibel declared having no relevant financial interests.

Adding the monoclonal antibody pertuzumab to standard neoadjuvant therapy with trastuzumab plus docetaxel increased the rate of complete tumor response in the proof-of-concept NeoSphere study of women with locally advanced, inflammatory, or early HER2-positive breast cancer, as published online Dec. 6 in Lancet Oncology.

The addition of pertuzumab, which has a different binding site and a complementary mechanism of action to trastuzumab (Herceptin), did not appear to increase the number or severity of treatment-related adverse events in the industry-sponsored, open-label, phase II study, said Dr. Luca Gianni of San Raffaele Cancer Centre in Milan (Italy), and his associates.

"The tumor response to this new triplet combination is one of the highest reported to date, despite just a short treatment time, and could be a big advance for women with HER2-positive disease," Dr. Gianni noted in a press statement accompanying the report.

In the international study, 417 treatment-naive patients at 59 medical centers were randomly assigned to receive 12 weeks of conventional therapy with neoadjuvant trastuzumab plus docetaxel (Taxotere), or pertuzumab and trastuzumab plus docetaxel, or pertuzumab and trastuzumab with no chemotherapy, or pertuzumab plus docetaxel before undergoing surgery. In all, 25 patients, "mostly in the chemotherapy-free group," did not complete surgery as planned. Following surgery, patients in all groups received adjuvant conventional treatment including anthracyclines and trastuzumab for 1 year.

The primary efficacy end point was complete pathologic response within the breast, defined as the absence of invasive neoplastic cells at microscopic examination of the primary tumor at surgery. This was achieved in 46% of women given the triplet, compared with only 29% of those given conventional therapy, 17% of those given both monoclonal antibodies but no chemotherapy, and 24% of those given pertuzumab plus chemotherapy.

Thus, the triplet was more effective than was conventional treatment, as well as being more effective than chemotherapy plus either monoclonal antibody alone, Dr. Gianni and his colleagues said (Lancet Oncol. 2011 Dec. 6 [doi:10.1016/S1470-2045(11)70336-9]).

The triplet was particularly effective in the subgroup of women with hormone receptor–negative tumors, with a complete response rate of 63%, they noted. In addition, dual HER2 blockade by pertuzumab and trastuzumab completely eradicated breast tumors in 27% of patients who did not receive docetaxel for these tumors.

The 17% complete response rate among all patients given both monoclonal antibodies without chemotherapy was notable. It suggests that a proportion of HER2-positive tumors can be eradicated without any chemotherapy, "which might have immediate use for women who cannot receive cytotoxic drugs," the investigators added.

Approximately one-third of this subgroup of patients did not respond to the dual-antibody regimen, and that may be attributable to the short duration of neoadjuvant treatment. This possibility will be assessed in clinical trials with longer-term therapy, the researchers said.

As expected with docetaxel, the most common adverse events of grade 3 or higher were neutropenia, febrile neutropenia, and leukopenia. The rates of adverse events (12%-14%) and serious adverse events (10%-17%) were similar across the three groups that received docetaxel, and were markedly lower in the group that didn’t receive it (2% and 4%, respectively).

In particular, cardiac toxicity was considered "good," but a longer observation period will be necessary to rule out the possibility that adding pertuzumab may increase cardiotoxicity. The mean maximal decrease in left ventricular ejection fraction (LVEF) was 4%-5% and was similar across all treatment groups. "No significant change was detected when pertuzumab was added to trastuzumab, and no patient had an LVEF decrease to less than 40% at any time during the study. Four patients [three receiving conventional therapy and one receiving triple-combination therapy] showed LVEF declines of 10%-15% from baseline and to less than 50% during the neoadjuvant period," Dr. Gianni and his associates said.

In July, Roche announced that it plans to see Food and Drug Administration approval based on a survival advantage for the triplet in the phase III CLEOPATRA trial. Data from that study will be presented this week at the San Antonio Breast Cancer Symposium.

This NeoSphere study was funded by Hoffmann-La Roche, maker of pertuzumab; the company provided the study drugs and was involved in the study design, safety monitoring and reporting, and data management and anaylsis. Fondazione Michelangelo also provided support. Dr. Gianni is an advisory board member for Roche, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Wyeth, and Novartis. Three coauthors are Roche employees; two disclosed Roche stock ownership.

Adding the monoclonal antibody pertuzumab to standard neoadjuvant therapy with trastuzumab plus docetaxel increased the rate of complete tumor response in the proof-of-concept NeoSphere study of women with locally advanced, inflammatory, or early HER2-positive breast cancer, as published online Dec. 6 in Lancet Oncology.

The addition of pertuzumab, which has a different binding site and a complementary mechanism of action to trastuzumab (Herceptin), did not appear to increase the number or severity of treatment-related adverse events in the industry-sponsored, open-label, phase II study, said Dr. Luca Gianni of San Raffaele Cancer Centre in Milan (Italy), and his associates.

"The tumor response to this new triplet combination is one of the highest reported to date, despite just a short treatment time, and could be a big advance for women with HER2-positive disease," Dr. Gianni noted in a press statement accompanying the report.

In the international study, 417 treatment-naive patients at 59 medical centers were randomly assigned to receive 12 weeks of conventional therapy with neoadjuvant trastuzumab plus docetaxel (Taxotere), or pertuzumab and trastuzumab plus docetaxel, or pertuzumab and trastuzumab with no chemotherapy, or pertuzumab plus docetaxel before undergoing surgery. In all, 25 patients, "mostly in the chemotherapy-free group," did not complete surgery as planned. Following surgery, patients in all groups received adjuvant conventional treatment including anthracyclines and trastuzumab for 1 year.

The primary efficacy end point was complete pathologic response within the breast, defined as the absence of invasive neoplastic cells at microscopic examination of the primary tumor at surgery. This was achieved in 46% of women given the triplet, compared with only 29% of those given conventional therapy, 17% of those given both monoclonal antibodies but no chemotherapy, and 24% of those given pertuzumab plus chemotherapy.

Thus, the triplet was more effective than was conventional treatment, as well as being more effective than chemotherapy plus either monoclonal antibody alone, Dr. Gianni and his colleagues said (Lancet Oncol. 2011 Dec. 6 [doi:10.1016/S1470-2045(11)70336-9]).

The triplet was particularly effective in the subgroup of women with hormone receptor–negative tumors, with a complete response rate of 63%, they noted. In addition, dual HER2 blockade by pertuzumab and trastuzumab completely eradicated breast tumors in 27% of patients who did not receive docetaxel for these tumors.

The 17% complete response rate among all patients given both monoclonal antibodies without chemotherapy was notable. It suggests that a proportion of HER2-positive tumors can be eradicated without any chemotherapy, "which might have immediate use for women who cannot receive cytotoxic drugs," the investigators added.

Approximately one-third of this subgroup of patients did not respond to the dual-antibody regimen, and that may be attributable to the short duration of neoadjuvant treatment. This possibility will be assessed in clinical trials with longer-term therapy, the researchers said.

As expected with docetaxel, the most common adverse events of grade 3 or higher were neutropenia, febrile neutropenia, and leukopenia. The rates of adverse events (12%-14%) and serious adverse events (10%-17%) were similar across the three groups that received docetaxel, and were markedly lower in the group that didn’t receive it (2% and 4%, respectively).

In particular, cardiac toxicity was considered "good," but a longer observation period will be necessary to rule out the possibility that adding pertuzumab may increase cardiotoxicity. The mean maximal decrease in left ventricular ejection fraction (LVEF) was 4%-5% and was similar across all treatment groups. "No significant change was detected when pertuzumab was added to trastuzumab, and no patient had an LVEF decrease to less than 40% at any time during the study. Four patients [three receiving conventional therapy and one receiving triple-combination therapy] showed LVEF declines of 10%-15% from baseline and to less than 50% during the neoadjuvant period," Dr. Gianni and his associates said.

In July, Roche announced that it plans to see Food and Drug Administration approval based on a survival advantage for the triplet in the phase III CLEOPATRA trial. Data from that study will be presented this week at the San Antonio Breast Cancer Symposium.

This NeoSphere study was funded by Hoffmann-La Roche, maker of pertuzumab; the company provided the study drugs and was involved in the study design, safety monitoring and reporting, and data management and anaylsis. Fondazione Michelangelo also provided support. Dr. Gianni is an advisory board member for Roche, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Wyeth, and Novartis. Three coauthors are Roche employees; two disclosed Roche stock ownership.

Adding the monoclonal antibody pertuzumab to standard neoadjuvant therapy with trastuzumab plus docetaxel increased the rate of complete tumor response in the proof-of-concept NeoSphere study of women with locally advanced, inflammatory, or early HER2-positive breast cancer, as published online Dec. 6 in Lancet Oncology.

The addition of pertuzumab, which has a different binding site and a complementary mechanism of action to trastuzumab (Herceptin), did not appear to increase the number or severity of treatment-related adverse events in the industry-sponsored, open-label, phase II study, said Dr. Luca Gianni of San Raffaele Cancer Centre in Milan (Italy), and his associates.

"The tumor response to this new triplet combination is one of the highest reported to date, despite just a short treatment time, and could be a big advance for women with HER2-positive disease," Dr. Gianni noted in a press statement accompanying the report.

In the international study, 417 treatment-naive patients at 59 medical centers were randomly assigned to receive 12 weeks of conventional therapy with neoadjuvant trastuzumab plus docetaxel (Taxotere), or pertuzumab and trastuzumab plus docetaxel, or pertuzumab and trastuzumab with no chemotherapy, or pertuzumab plus docetaxel before undergoing surgery. In all, 25 patients, "mostly in the chemotherapy-free group," did not complete surgery as planned. Following surgery, patients in all groups received adjuvant conventional treatment including anthracyclines and trastuzumab for 1 year.

The primary efficacy end point was complete pathologic response within the breast, defined as the absence of invasive neoplastic cells at microscopic examination of the primary tumor at surgery. This was achieved in 46% of women given the triplet, compared with only 29% of those given conventional therapy, 17% of those given both monoclonal antibodies but no chemotherapy, and 24% of those given pertuzumab plus chemotherapy.

Thus, the triplet was more effective than was conventional treatment, as well as being more effective than chemotherapy plus either monoclonal antibody alone, Dr. Gianni and his colleagues said (Lancet Oncol. 2011 Dec. 6 [doi:10.1016/S1470-2045(11)70336-9]).

The triplet was particularly effective in the subgroup of women with hormone receptor–negative tumors, with a complete response rate of 63%, they noted. In addition, dual HER2 blockade by pertuzumab and trastuzumab completely eradicated breast tumors in 27% of patients who did not receive docetaxel for these tumors.

The 17% complete response rate among all patients given both monoclonal antibodies without chemotherapy was notable. It suggests that a proportion of HER2-positive tumors can be eradicated without any chemotherapy, "which might have immediate use for women who cannot receive cytotoxic drugs," the investigators added.

Approximately one-third of this subgroup of patients did not respond to the dual-antibody regimen, and that may be attributable to the short duration of neoadjuvant treatment. This possibility will be assessed in clinical trials with longer-term therapy, the researchers said.

As expected with docetaxel, the most common adverse events of grade 3 or higher were neutropenia, febrile neutropenia, and leukopenia. The rates of adverse events (12%-14%) and serious adverse events (10%-17%) were similar across the three groups that received docetaxel, and were markedly lower in the group that didn’t receive it (2% and 4%, respectively).

In particular, cardiac toxicity was considered "good," but a longer observation period will be necessary to rule out the possibility that adding pertuzumab may increase cardiotoxicity. The mean maximal decrease in left ventricular ejection fraction (LVEF) was 4%-5% and was similar across all treatment groups. "No significant change was detected when pertuzumab was added to trastuzumab, and no patient had an LVEF decrease to less than 40% at any time during the study. Four patients [three receiving conventional therapy and one receiving triple-combination therapy] showed LVEF declines of 10%-15% from baseline and to less than 50% during the neoadjuvant period," Dr. Gianni and his associates said.

In July, Roche announced that it plans to see Food and Drug Administration approval based on a survival advantage for the triplet in the phase III CLEOPATRA trial. Data from that study will be presented this week at the San Antonio Breast Cancer Symposium.

This NeoSphere study was funded by Hoffmann-La Roche, maker of pertuzumab; the company provided the study drugs and was involved in the study design, safety monitoring and reporting, and data management and anaylsis. Fondazione Michelangelo also provided support. Dr. Gianni is an advisory board member for Roche, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Wyeth, and Novartis. Three coauthors are Roche employees; two disclosed Roche stock ownership.

The 2011 San Antonio Breast Cancer Symposium that opened Dec. 6 features a hefty number of studies that could change clinical practice in the treatment of breast cancer.

Oncologists have been eagerly awaiting data from the phase III BOLERO-2 and CLEOPATRA trials, which are to be presented Dec. 8 and 9, respectively.

– BOLERO-2 investigators reported that pairing everolimus (Afinitor) with exemestane (Aromasin) increased median progression-free survival by 4.1 months in an interim analysis presented this fall at the European Multidisciplinary Cancer Congress in Stockholm. Women in this study had estrogen receptor-positive disease that was resistant to hormone therapy.

– Genentech announced last summer that dual HER2 blockade with pertuzumab* and trastuzumab (Herceptin) improved progression-free survival for women with HER2-positive disease who also received docetaxel (Taxotere) in CLEOPATRA. The pairing has also produced good results in the NeoSphere trial, and early reports from studies pairing lapatinib (Tykerb) with trastuzumab have been encouraging.

On Dec. 7, an early-morning press briefing has been scheduled for investigators to outline findings of four noteworthy studies.

– Swedish researchers will report that diabetes and obesity after age 60 are risk factors for breast cancer. Low lipids also increased risk, but high lipids did not in their study comparing medical records of more than 23,000 women. Similarly, risk went up with use of the diabetes drug glargine but down with metformin.

– Gene expression patterns at diagnosis of hormone receptor–positive breast cancer can predict which women will have recurrences late, early, or not at all, according to researchers from the United States.

– Women treated with brachytherapy were about twice as likely to undergo subsequent mastectomy when compared with those treated by whole breast irradiation in a study of more than 150,000 Medicare claims.

– A ductal carcinoma in situ (DCIS) risk score based on the multigene Oncotype DX assay has been validated for prediction of breast cancer recurrence in DCIS patients.

Other Dec. 7 highlights will include presentations from four studies of bisphosphonate use in breast cancer patients and an Institute of Medicine report on "Breast Cancer and the Environment."

For ongoing coverage of these and other presentations at the San Antonio Breast Cancer Symposium, visit http://www.oncologyreport.com.

*Correction, Dec. 8, 2011: An earlier version of this story referred to pertuzumab by the trade name Omnitarg. That trade name was discontinued by Genentech in 2007 and currently the drug goes by pertuzumab.

The 2011 San Antonio Breast Cancer Symposium that opened Dec. 6 features a hefty number of studies that could change clinical practice in the treatment of breast cancer.

Oncologists have been eagerly awaiting data from the phase III BOLERO-2 and CLEOPATRA trials, which are to be presented Dec. 8 and 9, respectively.

– BOLERO-2 investigators reported that pairing everolimus (Afinitor) with exemestane (Aromasin) increased median progression-free survival by 4.1 months in an interim analysis presented this fall at the European Multidisciplinary Cancer Congress in Stockholm. Women in this study had estrogen receptor-positive disease that was resistant to hormone therapy.

– Genentech announced last summer that dual HER2 blockade with pertuzumab* and trastuzumab (Herceptin) improved progression-free survival for women with HER2-positive disease who also received docetaxel (Taxotere) in CLEOPATRA. The pairing has also produced good results in the NeoSphere trial, and early reports from studies pairing lapatinib (Tykerb) with trastuzumab have been encouraging.

On Dec. 7, an early-morning press briefing has been scheduled for investigators to outline findings of four noteworthy studies.

– Swedish researchers will report that diabetes and obesity after age 60 are risk factors for breast cancer. Low lipids also increased risk, but high lipids did not in their study comparing medical records of more than 23,000 women. Similarly, risk went up with use of the diabetes drug glargine but down with metformin.

– Gene expression patterns at diagnosis of hormone receptor–positive breast cancer can predict which women will have recurrences late, early, or not at all, according to researchers from the United States.

– Women treated with brachytherapy were about twice as likely to undergo subsequent mastectomy when compared with those treated by whole breast irradiation in a study of more than 150,000 Medicare claims.

– A ductal carcinoma in situ (DCIS) risk score based on the multigene Oncotype DX assay has been validated for prediction of breast cancer recurrence in DCIS patients.

Other Dec. 7 highlights will include presentations from four studies of bisphosphonate use in breast cancer patients and an Institute of Medicine report on "Breast Cancer and the Environment."

For ongoing coverage of these and other presentations at the San Antonio Breast Cancer Symposium, visit http://www.oncologyreport.com.

*Correction, Dec. 8, 2011: An earlier version of this story referred to pertuzumab by the trade name Omnitarg. That trade name was discontinued by Genentech in 2007 and currently the drug goes by pertuzumab.

The 2011 San Antonio Breast Cancer Symposium that opened Dec. 6 features a hefty number of studies that could change clinical practice in the treatment of breast cancer.

Oncologists have been eagerly awaiting data from the phase III BOLERO-2 and CLEOPATRA trials, which are to be presented Dec. 8 and 9, respectively.

– BOLERO-2 investigators reported that pairing everolimus (Afinitor) with exemestane (Aromasin) increased median progression-free survival by 4.1 months in an interim analysis presented this fall at the European Multidisciplinary Cancer Congress in Stockholm. Women in this study had estrogen receptor-positive disease that was resistant to hormone therapy.

– Genentech announced last summer that dual HER2 blockade with pertuzumab* and trastuzumab (Herceptin) improved progression-free survival for women with HER2-positive disease who also received docetaxel (Taxotere) in CLEOPATRA. The pairing has also produced good results in the NeoSphere trial, and early reports from studies pairing lapatinib (Tykerb) with trastuzumab have been encouraging.

On Dec. 7, an early-morning press briefing has been scheduled for investigators to outline findings of four noteworthy studies.

– Swedish researchers will report that diabetes and obesity after age 60 are risk factors for breast cancer. Low lipids also increased risk, but high lipids did not in their study comparing medical records of more than 23,000 women. Similarly, risk went up with use of the diabetes drug glargine but down with metformin.

– Gene expression patterns at diagnosis of hormone receptor–positive breast cancer can predict which women will have recurrences late, early, or not at all, according to researchers from the United States.

– Women treated with brachytherapy were about twice as likely to undergo subsequent mastectomy when compared with those treated by whole breast irradiation in a study of more than 150,000 Medicare claims.

– A ductal carcinoma in situ (DCIS) risk score based on the multigene Oncotype DX assay has been validated for prediction of breast cancer recurrence in DCIS patients.

Other Dec. 7 highlights will include presentations from four studies of bisphosphonate use in breast cancer patients and an Institute of Medicine report on "Breast Cancer and the Environment."

For ongoing coverage of these and other presentations at the San Antonio Breast Cancer Symposium, visit http://www.oncologyreport.com.

*Correction, Dec. 8, 2011: An earlier version of this story referred to pertuzumab by the trade name Omnitarg. That trade name was discontinued by Genentech in 2007 and currently the drug goes by pertuzumab.

Scant research has focused on breast cancer in very young women. This retrospective case series by investigators at the Mayo Clinic assessed girls and women younger than 25 years who were given a diagnosis of primary breast cancer between 1935 and 2005 and who received care at that institution.

The investigators highlighted many of the challenges clinicians face when a young patient presents with a lump or other signs associated with breast cancer. For example, they note that, in its early stages, breast carcinoma in young women can be similar in appearance to fibroadenoma. When a patient postpones care or a clinician dismisses the lump because of a low index of suspicion, diagnosis can be delayed. That is problematic because invasive breast carcinoma in girls and young women is more aggressive and associated with a poorer prognosis overall.

Details of the trial

Eleven women 20 to 24 years old and one 18-year-old teen were found to have breast cancer. Of these, eight of the women detected the mass themselves, one observed bloody nipple discharge associated with constitutional symptoms, and another experienced severe constitutional symptoms associated with disseminated malignancy. In one case, the physician detected a breast mass in an asymptomatic woman. Details on the remaining woman were unavailable.

Palpable masses were noted in most of the women at the time of clinical evaluation, and the median greatest diameter was 4 cm. After the original history and exam, breast cancer was suspected in only 2 of the 11 women.

Among the 11 young women who had breast cancer, one had received mantle and abdominal radiotherapy for previously diagnosed Hodgkin’s disease. Two women had a family history suggesting hereditary breast cancer. None of the women were tested for a BRCA mutation. Regional or local recurrence was identified in three women, and contralateral breast cancer was found in two women (one of whom was subsequently also found to have ovarian cancer). At the time of the last follow-up (a median of 25.5 months), four women had died as a result of breast cancer, one had died from advanced ovarian cancer, two were alive with disease, and five were alive with no evidence of disease.

We want to hear from you! Tell us what you think.

Scant research has focused on breast cancer in very young women. This retrospective case series by investigators at the Mayo Clinic assessed girls and women younger than 25 years who were given a diagnosis of primary breast cancer between 1935 and 2005 and who received care at that institution.

The investigators highlighted many of the challenges clinicians face when a young patient presents with a lump or other signs associated with breast cancer. For example, they note that, in its early stages, breast carcinoma in young women can be similar in appearance to fibroadenoma. When a patient postpones care or a clinician dismisses the lump because of a low index of suspicion, diagnosis can be delayed. That is problematic because invasive breast carcinoma in girls and young women is more aggressive and associated with a poorer prognosis overall.

Details of the trial

Eleven women 20 to 24 years old and one 18-year-old teen were found to have breast cancer. Of these, eight of the women detected the mass themselves, one observed bloody nipple discharge associated with constitutional symptoms, and another experienced severe constitutional symptoms associated with disseminated malignancy. In one case, the physician detected a breast mass in an asymptomatic woman. Details on the remaining woman were unavailable.

Palpable masses were noted in most of the women at the time of clinical evaluation, and the median greatest diameter was 4 cm. After the original history and exam, breast cancer was suspected in only 2 of the 11 women.

Among the 11 young women who had breast cancer, one had received mantle and abdominal radiotherapy for previously diagnosed Hodgkin’s disease. Two women had a family history suggesting hereditary breast cancer. None of the women were tested for a BRCA mutation. Regional or local recurrence was identified in three women, and contralateral breast cancer was found in two women (one of whom was subsequently also found to have ovarian cancer). At the time of the last follow-up (a median of 25.5 months), four women had died as a result of breast cancer, one had died from advanced ovarian cancer, two were alive with disease, and five were alive with no evidence of disease.

We want to hear from you! Tell us what you think.

Scant research has focused on breast cancer in very young women. This retrospective case series by investigators at the Mayo Clinic assessed girls and women younger than 25 years who were given a diagnosis of primary breast cancer between 1935 and 2005 and who received care at that institution.

The investigators highlighted many of the challenges clinicians face when a young patient presents with a lump or other signs associated with breast cancer. For example, they note that, in its early stages, breast carcinoma in young women can be similar in appearance to fibroadenoma. When a patient postpones care or a clinician dismisses the lump because of a low index of suspicion, diagnosis can be delayed. That is problematic because invasive breast carcinoma in girls and young women is more aggressive and associated with a poorer prognosis overall.

Details of the trial

Eleven women 20 to 24 years old and one 18-year-old teen were found to have breast cancer. Of these, eight of the women detected the mass themselves, one observed bloody nipple discharge associated with constitutional symptoms, and another experienced severe constitutional symptoms associated with disseminated malignancy. In one case, the physician detected a breast mass in an asymptomatic woman. Details on the remaining woman were unavailable.

Palpable masses were noted in most of the women at the time of clinical evaluation, and the median greatest diameter was 4 cm. After the original history and exam, breast cancer was suspected in only 2 of the 11 women.

Among the 11 young women who had breast cancer, one had received mantle and abdominal radiotherapy for previously diagnosed Hodgkin’s disease. Two women had a family history suggesting hereditary breast cancer. None of the women were tested for a BRCA mutation. Regional or local recurrence was identified in three women, and contralateral breast cancer was found in two women (one of whom was subsequently also found to have ovarian cancer). At the time of the last follow-up (a median of 25.5 months), four women had died as a result of breast cancer, one had died from advanced ovarian cancer, two were alive with disease, and five were alive with no evidence of disease.

We want to hear from you! Tell us what you think.

Legislation introduced in the U.S. House of Representatives would require that women be informed of their breast density when they receive their mammogram results, and that those with denser breasts be advised that they could benefit from additional screening.

The Breast Density and Mammography Reporting Act of 2011 (H.R. 3102), introduced in October by Rep. Rosa DeLauro (D-Conn.) and Rep. Steve Israel (D-N.Y.), is modeled after laws enacted in Connecticut in 2009 and in Texas earlier this year. Similar legislation was recently passed by the California legislature, but was vetoed by the governor.

Bills on breast density are also slated to be introduced in at least six other states next year, according to the consumer advocacy group Are You Dense.

The movement to pass these bills has grown largely from the outrage of women who have received years of normal mammogram results only to find out that they have an advanced-stage breast cancer that went undetected because of their dense breast tissue.

That was the experience of Are You Dense founder Nancy M. Cappello, Ph.D., who successfully lobbied lawmakers to enact the Connecticut legislation.

Although information on breast density is available on the mammography report sent to referring physicians, it's not mentioned in the “lay letter” received by women, Dr. Cappello said. That leaves most women in the dark about the fact that dense breasts can make mammograms more difficult to read, and that women with extremely dense breasts are at a higher risk for breast cancer, she said.

“It's a hoax in some respects, a cruel hoax,” she said.

Are You Dense and its supporters around the country have been working state by state to enact laws that require that women be notified of their breast density and their options for additional screening. They are also working at the federal level to change either the law or the regulations surrounding mammography.

Dr. Cappello said that trying to legislate the change wasn't her first choice, but without a national cancer organization or physician group stepping up to educate women, she doesn't have a better option for standardizing the communication on breast density.

In November, Dr. Cappello took her case to the Food and Drug Administration's National Mammography Quality Assurance Advisory Committee. The asked the committee, which provides nonbinding advice to the FDA, to recommend changing the federally mandated lay letter to include information on breast density. While the advisory committee members reached a consensus that breast tissue density should be reported in the mammography lay letter, several of the members said they were unsure what recommendation could be made to physicians and patients about what to do with the information. The committee also did not come to an agreement on the best say to further evaluate patients with dense breasts through other imaging modalities.

But given the uncertain timeframe for any action by the FDA, Are You Dense plans to continue its efforts to enact breast density legislation in the states and at the federal level.

So far, Dr. Cappello's legislative efforts have failed to gain support from major physician groups and patient advocacy organizations. Susan G. Komen for the Cure and the American Cancer Society both stayed on the sidelines during the recent legislative debate in California. The California chapter of the American College of Obstetricians and Gynecologists and the California Medical Association opposed the bill.

“It was a very difficult bill for us to oppose,” said Dr. Philip Diamond, a San Diego ob.gyn. and chair of ACOG District IX in California.

The problem was that the bill went beyond notifying women about their density and on to suggest that they speak with their physician about supplemental screening. The bill's language on supplemental screening goes beyond the existing evidence, Dr. Diamond said, and raised a host of concerns about what the cost of screening would mean for state-funded health programs.

“In the absence of a guideline nationally by either the cancer society or the radiology society or anyone, it's impossible to be able to figure out who needs supplement screening and who doesn't,” he said.

A big concern in California, Dr. Diamond said, is that such legislation would lead to the automatic ordering of supplemental ultrasounds and MRIs, regardless of the individual risk factors of the women involved.

That's exactly what has happened after the Connecticut law was enacted, according to New Haven ob.gyn. Howard Shaw, vice chair for the Connecticut section of ACOG.

Although the law has probably raised some awareness of the breast density issues for women, it has also sparked a reflexive ordering of supplemental testing for any women with dense breasts, he said, adding that the ordering is largely driven by liability concerns.

“There is a feeling by many that we're just going to order it because, if we don't order it and something happens, we're going to have a problem,” said Dr. Steven Fleischman, associate chief of ob.gyn. at Yale–New Haven Hospital and the legislative chair of ACOG District I.

Another problem with the Connecticut law is that there's a lack of data on how it's working, he said. Because there was no tracking component built into the law, there are many lingering questions about the number of supplemental tests, the additional costs, and whether more cancers are being detected earlier, he said.

“It's not just about cost; it's about 'Are we getting more cases, and are we getting them earlier,'” Dr. Fleischman said.

The digital mammogram (left) was negative, while the molecular breast imaging scan detected a ductal carcinoma in situ in this dense breast.

Source Courtesy Mayo Clinic

Legislation introduced in the U.S. House of Representatives would require that women be informed of their breast density when they receive their mammogram results, and that those with denser breasts be advised that they could benefit from additional screening.

The Breast Density and Mammography Reporting Act of 2011 (H.R. 3102), introduced in October by Rep. Rosa DeLauro (D-Conn.) and Rep. Steve Israel (D-N.Y.), is modeled after laws enacted in Connecticut in 2009 and in Texas earlier this year. Similar legislation was recently passed by the California legislature, but was vetoed by the governor.

Bills on breast density are also slated to be introduced in at least six other states next year, according to the consumer advocacy group Are You Dense.

The movement to pass these bills has grown largely from the outrage of women who have received years of normal mammogram results only to find out that they have an advanced-stage breast cancer that went undetected because of their dense breast tissue.

That was the experience of Are You Dense founder Nancy M. Cappello, Ph.D., who successfully lobbied lawmakers to enact the Connecticut legislation.

Although information on breast density is available on the mammography report sent to referring physicians, it's not mentioned in the “lay letter” received by women, Dr. Cappello said. That leaves most women in the dark about the fact that dense breasts can make mammograms more difficult to read, and that women with extremely dense breasts are at a higher risk for breast cancer, she said.

“It's a hoax in some respects, a cruel hoax,” she said.

Are You Dense and its supporters around the country have been working state by state to enact laws that require that women be notified of their breast density and their options for additional screening. They are also working at the federal level to change either the law or the regulations surrounding mammography.

Dr. Cappello said that trying to legislate the change wasn't her first choice, but without a national cancer organization or physician group stepping up to educate women, she doesn't have a better option for standardizing the communication on breast density.

In November, Dr. Cappello took her case to the Food and Drug Administration's National Mammography Quality Assurance Advisory Committee. The asked the committee, which provides nonbinding advice to the FDA, to recommend changing the federally mandated lay letter to include information on breast density. While the advisory committee members reached a consensus that breast tissue density should be reported in the mammography lay letter, several of the members said they were unsure what recommendation could be made to physicians and patients about what to do with the information. The committee also did not come to an agreement on the best say to further evaluate patients with dense breasts through other imaging modalities.

But given the uncertain timeframe for any action by the FDA, Are You Dense plans to continue its efforts to enact breast density legislation in the states and at the federal level.

So far, Dr. Cappello's legislative efforts have failed to gain support from major physician groups and patient advocacy organizations. Susan G. Komen for the Cure and the American Cancer Society both stayed on the sidelines during the recent legislative debate in California. The California chapter of the American College of Obstetricians and Gynecologists and the California Medical Association opposed the bill.

“It was a very difficult bill for us to oppose,” said Dr. Philip Diamond, a San Diego ob.gyn. and chair of ACOG District IX in California.

The problem was that the bill went beyond notifying women about their density and on to suggest that they speak with their physician about supplemental screening. The bill's language on supplemental screening goes beyond the existing evidence, Dr. Diamond said, and raised a host of concerns about what the cost of screening would mean for state-funded health programs.

“In the absence of a guideline nationally by either the cancer society or the radiology society or anyone, it's impossible to be able to figure out who needs supplement screening and who doesn't,” he said.

A big concern in California, Dr. Diamond said, is that such legislation would lead to the automatic ordering of supplemental ultrasounds and MRIs, regardless of the individual risk factors of the women involved.

That's exactly what has happened after the Connecticut law was enacted, according to New Haven ob.gyn. Howard Shaw, vice chair for the Connecticut section of ACOG.

Although the law has probably raised some awareness of the breast density issues for women, it has also sparked a reflexive ordering of supplemental testing for any women with dense breasts, he said, adding that the ordering is largely driven by liability concerns.

“There is a feeling by many that we're just going to order it because, if we don't order it and something happens, we're going to have a problem,” said Dr. Steven Fleischman, associate chief of ob.gyn. at Yale–New Haven Hospital and the legislative chair of ACOG District I.

Another problem with the Connecticut law is that there's a lack of data on how it's working, he said. Because there was no tracking component built into the law, there are many lingering questions about the number of supplemental tests, the additional costs, and whether more cancers are being detected earlier, he said.

“It's not just about cost; it's about 'Are we getting more cases, and are we getting them earlier,'” Dr. Fleischman said.

The digital mammogram (left) was negative, while the molecular breast imaging scan detected a ductal carcinoma in situ in this dense breast.

Source Courtesy Mayo Clinic

Legislation introduced in the U.S. House of Representatives would require that women be informed of their breast density when they receive their mammogram results, and that those with denser breasts be advised that they could benefit from additional screening.

The Breast Density and Mammography Reporting Act of 2011 (H.R. 3102), introduced in October by Rep. Rosa DeLauro (D-Conn.) and Rep. Steve Israel (D-N.Y.), is modeled after laws enacted in Connecticut in 2009 and in Texas earlier this year. Similar legislation was recently passed by the California legislature, but was vetoed by the governor.

Bills on breast density are also slated to be introduced in at least six other states next year, according to the consumer advocacy group Are You Dense.

The movement to pass these bills has grown largely from the outrage of women who have received years of normal mammogram results only to find out that they have an advanced-stage breast cancer that went undetected because of their dense breast tissue.

That was the experience of Are You Dense founder Nancy M. Cappello, Ph.D., who successfully lobbied lawmakers to enact the Connecticut legislation.

Although information on breast density is available on the mammography report sent to referring physicians, it's not mentioned in the “lay letter” received by women, Dr. Cappello said. That leaves most women in the dark about the fact that dense breasts can make mammograms more difficult to read, and that women with extremely dense breasts are at a higher risk for breast cancer, she said.

“It's a hoax in some respects, a cruel hoax,” she said.

Are You Dense and its supporters around the country have been working state by state to enact laws that require that women be notified of their breast density and their options for additional screening. They are also working at the federal level to change either the law or the regulations surrounding mammography.

Dr. Cappello said that trying to legislate the change wasn't her first choice, but without a national cancer organization or physician group stepping up to educate women, she doesn't have a better option for standardizing the communication on breast density.

In November, Dr. Cappello took her case to the Food and Drug Administration's National Mammography Quality Assurance Advisory Committee. The asked the committee, which provides nonbinding advice to the FDA, to recommend changing the federally mandated lay letter to include information on breast density. While the advisory committee members reached a consensus that breast tissue density should be reported in the mammography lay letter, several of the members said they were unsure what recommendation could be made to physicians and patients about what to do with the information. The committee also did not come to an agreement on the best say to further evaluate patients with dense breasts through other imaging modalities.

But given the uncertain timeframe for any action by the FDA, Are You Dense plans to continue its efforts to enact breast density legislation in the states and at the federal level.

So far, Dr. Cappello's legislative efforts have failed to gain support from major physician groups and patient advocacy organizations. Susan G. Komen for the Cure and the American Cancer Society both stayed on the sidelines during the recent legislative debate in California. The California chapter of the American College of Obstetricians and Gynecologists and the California Medical Association opposed the bill.

“It was a very difficult bill for us to oppose,” said Dr. Philip Diamond, a San Diego ob.gyn. and chair of ACOG District IX in California.

The problem was that the bill went beyond notifying women about their density and on to suggest that they speak with their physician about supplemental screening. The bill's language on supplemental screening goes beyond the existing evidence, Dr. Diamond said, and raised a host of concerns about what the cost of screening would mean for state-funded health programs.

“In the absence of a guideline nationally by either the cancer society or the radiology society or anyone, it's impossible to be able to figure out who needs supplement screening and who doesn't,” he said.

A big concern in California, Dr. Diamond said, is that such legislation would lead to the automatic ordering of supplemental ultrasounds and MRIs, regardless of the individual risk factors of the women involved.

That's exactly what has happened after the Connecticut law was enacted, according to New Haven ob.gyn. Howard Shaw, vice chair for the Connecticut section of ACOG.

Although the law has probably raised some awareness of the breast density issues for women, it has also sparked a reflexive ordering of supplemental testing for any women with dense breasts, he said, adding that the ordering is largely driven by liability concerns.

“There is a feeling by many that we're just going to order it because, if we don't order it and something happens, we're going to have a problem,” said Dr. Steven Fleischman, associate chief of ob.gyn. at Yale–New Haven Hospital and the legislative chair of ACOG District I.

Another problem with the Connecticut law is that there's a lack of data on how it's working, he said. Because there was no tracking component built into the law, there are many lingering questions about the number of supplemental tests, the additional costs, and whether more cancers are being detected earlier, he said.

“It's not just about cost; it's about 'Are we getting more cases, and are we getting them earlier,'” Dr. Fleischman said.

The digital mammogram (left) was negative, while the molecular breast imaging scan detected a ductal carcinoma in situ in this dense breast.

Source Courtesy Mayo Clinic

Family history data support annual mammograms in 40s

Women aged 40–49 years with and without a family history of breast cancer had almost the same rates of invasive disease in a retrospective analysis of data on more than 1,000 patients diagnosed over a 10-year period at a single site.

The finding adds weight to the American Cancer Society’s recommendation in favor of annual screening mammograms for women beginning at age 40, said principal author Dr. Stamatia V. Destounis of Elizabeth Wende Breast Care LLC in Rochester, NY. Dr. Destounis presented the results of her study in a press briefing.

A study presented at last year’s meeting by researchers at the London Breast Institute of the Princess Grace Hospital indicated that annual mammograms could reduce by half the risk of mastectomy in women who were diagnosed with breast cancer between the ages of 40 and 50 years.

Both studies challenge the recommendation against routine annual mammography for women under the age of 50 made in 2009 by the US Preventive Services Task Force. ...

* For a PDF of the full article, click in the link to the left of this introduction.

Family history data support annual mammograms in 40s

Women aged 40–49 years with and without a family history of breast cancer had almost the same rates of invasive disease in a retrospective analysis of data on more than 1,000 patients diagnosed over a 10-year period at a single site.

The finding adds weight to the American Cancer Society’s recommendation in favor of annual screening mammograms for women beginning at age 40, said principal author Dr. Stamatia V. Destounis of Elizabeth Wende Breast Care LLC in Rochester, NY. Dr. Destounis presented the results of her study in a press briefing.

A study presented at last year’s meeting by researchers at the London Breast Institute of the Princess Grace Hospital indicated that annual mammograms could reduce by half the risk of mastectomy in women who were diagnosed with breast cancer between the ages of 40 and 50 years.

Both studies challenge the recommendation against routine annual mammography for women under the age of 50 made in 2009 by the US Preventive Services Task Force. ...

* For a PDF of the full article, click in the link to the left of this introduction.

Family history data support annual mammograms in 40s

Women aged 40–49 years with and without a family history of breast cancer had almost the same rates of invasive disease in a retrospective analysis of data on more than 1,000 patients diagnosed over a 10-year period at a single site.

The finding adds weight to the American Cancer Society’s recommendation in favor of annual screening mammograms for women beginning at age 40, said principal author Dr. Stamatia V. Destounis of Elizabeth Wende Breast Care LLC in Rochester, NY. Dr. Destounis presented the results of her study in a press briefing.

A study presented at last year’s meeting by researchers at the London Breast Institute of the Princess Grace Hospital indicated that annual mammograms could reduce by half the risk of mastectomy in women who were diagnosed with breast cancer between the ages of 40 and 50 years.

Both studies challenge the recommendation against routine annual mammography for women under the age of 50 made in 2009 by the US Preventive Services Task Force. ...

* For a PDF of the full article, click in the link to the left of this introduction.