SABCS 2011

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.

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.