SABCS 2014

SAN ANTONIO – In a roundtable at the 2014 San Antonio Breast Cancer Symposium, Dr. Jame Abraham, Dr. Linda Bosserman, and Dr. Debra Patt discussed their top selections from the meeting’s presentations.

Among the topics were the promising findings in a small study involving the novel immune checkpoint inhibitor pembrolizumab in advanced triple-negative breast cancer; the SOFT trial, which looked at ovarian suppression with either tamoxifen or an aromatase inhibitor in premenopausal women with hormone receptor–positive disease; and the negative findings on the use of erythropoietin in patients with metastatic breast cancer.

The editors also highlighted findings showing no difference in disease-free survival between node-negative patients receiving six cycles of 5-fluorouracil, epirubicin, and cyclophosphamide and those receiving four cycles of Adriamycin and cyclophosphamide; and data from the Women’s Intervention Nutrition Study, which showed that lifestyle and dietary changes can have a notable impact on outcomes in women with early-stage, treated breast cancer.

Management of therapy side effects, fertility concerns in younger patients, patient quality of life, and the cost effectiveness of treatment were a subtext to the editors’ discussions of the clinical findings, as they highlighted the importance of looking closely at the risk-benefit relationship in delivering quality, affordable, personalized care to patients with breast cancer.

Dr. Abraham is director of the breast medical oncology at the Cleveland Clinic. Dr. Bosserman is clinical assistant professor at City of Hope Cancer Center, Duarte, Calif. Dr. Patt is a partner at Texas Oncology, Austin, and director of health care informatics at McKesson Specialty Health.

[email protected]

SAN ANTONIO – In a roundtable at the 2014 San Antonio Breast Cancer Symposium, Dr. Jame Abraham, Dr. Linda Bosserman, and Dr. Debra Patt discussed their top selections from the meeting’s presentations.

Among the topics were the promising findings in a small study involving the novel immune checkpoint inhibitor pembrolizumab in advanced triple-negative breast cancer; the SOFT trial, which looked at ovarian suppression with either tamoxifen or an aromatase inhibitor in premenopausal women with hormone receptor–positive disease; and the negative findings on the use of erythropoietin in patients with metastatic breast cancer.

The editors also highlighted findings showing no difference in disease-free survival between node-negative patients receiving six cycles of 5-fluorouracil, epirubicin, and cyclophosphamide and those receiving four cycles of Adriamycin and cyclophosphamide; and data from the Women’s Intervention Nutrition Study, which showed that lifestyle and dietary changes can have a notable impact on outcomes in women with early-stage, treated breast cancer.

Management of therapy side effects, fertility concerns in younger patients, patient quality of life, and the cost effectiveness of treatment were a subtext to the editors’ discussions of the clinical findings, as they highlighted the importance of looking closely at the risk-benefit relationship in delivering quality, affordable, personalized care to patients with breast cancer.

Dr. Abraham is director of the breast medical oncology at the Cleveland Clinic. Dr. Bosserman is clinical assistant professor at City of Hope Cancer Center, Duarte, Calif. Dr. Patt is a partner at Texas Oncology, Austin, and director of health care informatics at McKesson Specialty Health.

[email protected]

SAN ANTONIO – In a roundtable at the 2014 San Antonio Breast Cancer Symposium, Dr. Jame Abraham, Dr. Linda Bosserman, and Dr. Debra Patt discussed their top selections from the meeting’s presentations.

Among the topics were the promising findings in a small study involving the novel immune checkpoint inhibitor pembrolizumab in advanced triple-negative breast cancer; the SOFT trial, which looked at ovarian suppression with either tamoxifen or an aromatase inhibitor in premenopausal women with hormone receptor–positive disease; and the negative findings on the use of erythropoietin in patients with metastatic breast cancer.

The editors also highlighted findings showing no difference in disease-free survival between node-negative patients receiving six cycles of 5-fluorouracil, epirubicin, and cyclophosphamide and those receiving four cycles of Adriamycin and cyclophosphamide; and data from the Women’s Intervention Nutrition Study, which showed that lifestyle and dietary changes can have a notable impact on outcomes in women with early-stage, treated breast cancer.

Management of therapy side effects, fertility concerns in younger patients, patient quality of life, and the cost effectiveness of treatment were a subtext to the editors’ discussions of the clinical findings, as they highlighted the importance of looking closely at the risk-benefit relationship in delivering quality, affordable, personalized care to patients with breast cancer.

Dr. Abraham is director of the breast medical oncology at the Cleveland Clinic. Dr. Bosserman is clinical assistant professor at City of Hope Cancer Center, Duarte, Calif. Dr. Patt is a partner at Texas Oncology, Austin, and director of health care informatics at McKesson Specialty Health.

[email protected]

SAN ANTONIO – Patients with stage T1a or T1b triple-negative breast cancer have an excellent prognosis even without chemotherapy, according to Dr. Eric P. Winer.

“There’s a perception on the part of many patients and physicians that all triple-negative breast cancer is bad, and that it’s destined to threaten and ultimately take a woman’s life. But even in an era where biology is king, stage still matters,” he observed at the San Antonio Breast Cancer Symposium.

He was a coinvestigator in a recent prospective cohort study which included 4,113 women with stage T1a or 1b breast cancer – that is, a tumor size no greater than 10 mm in its greatest dimension – without regional lymph node metastases or evidence of distant metastases. The patients, drawn from the National Comprehensive Cancer Network database, were treated in accord with institutional practice and followed for a median of 5.5 years.

Slightly over half of those in the subset with triple-negative breast cancer (TNBC) got chemotherapy. Those who received chemotherapy for T1a TNBC as defined by a tumor size not greater than 5 mm had a 5-year distant relapse-free survival (DRFS) of 100%, but the rate was still close to 95% in those not treated with chemotherapy. Outcomes were also quite favorable for patients with T1b TNBC who didn’t receive chemotherapy (J. Clin. Oncol. 2014;32:2142-50), said Dr. Winer, chief of the division of women’s cancers at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, Boston.

He noted that the findings in this study echo those of an earlier study by investigators at University of Texas M.D. Anderson Cancer Center, Houston, who reported a 5-year DRFS rate of 96% in 125 patients with T1a or 1b, lymph node-negative TNBC untreated with chemotherapy (J. Clin. Oncol. 2009;27:5700-6).

Dr. Winer said that while the consensus among most experts is that standard adjuvant chemotherapy regimens for patients with stage 2 or 3 TNBC include both anthracyclines and taxanes, his own view is that for patients with stage 1 TNBC “if you’re going to pursue chemotherapy, then treatment with a somewhat less toxic, shorter regimen would seem to be more appropriate.”

[email protected]

SAN ANTONIO – Patients with stage T1a or T1b triple-negative breast cancer have an excellent prognosis even without chemotherapy, according to Dr. Eric P. Winer.

“There’s a perception on the part of many patients and physicians that all triple-negative breast cancer is bad, and that it’s destined to threaten and ultimately take a woman’s life. But even in an era where biology is king, stage still matters,” he observed at the San Antonio Breast Cancer Symposium.

He was a coinvestigator in a recent prospective cohort study which included 4,113 women with stage T1a or 1b breast cancer – that is, a tumor size no greater than 10 mm in its greatest dimension – without regional lymph node metastases or evidence of distant metastases. The patients, drawn from the National Comprehensive Cancer Network database, were treated in accord with institutional practice and followed for a median of 5.5 years.

Slightly over half of those in the subset with triple-negative breast cancer (TNBC) got chemotherapy. Those who received chemotherapy for T1a TNBC as defined by a tumor size not greater than 5 mm had a 5-year distant relapse-free survival (DRFS) of 100%, but the rate was still close to 95% in those not treated with chemotherapy. Outcomes were also quite favorable for patients with T1b TNBC who didn’t receive chemotherapy (J. Clin. Oncol. 2014;32:2142-50), said Dr. Winer, chief of the division of women’s cancers at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, Boston.

He noted that the findings in this study echo those of an earlier study by investigators at University of Texas M.D. Anderson Cancer Center, Houston, who reported a 5-year DRFS rate of 96% in 125 patients with T1a or 1b, lymph node-negative TNBC untreated with chemotherapy (J. Clin. Oncol. 2009;27:5700-6).

Dr. Winer said that while the consensus among most experts is that standard adjuvant chemotherapy regimens for patients with stage 2 or 3 TNBC include both anthracyclines and taxanes, his own view is that for patients with stage 1 TNBC “if you’re going to pursue chemotherapy, then treatment with a somewhat less toxic, shorter regimen would seem to be more appropriate.”

[email protected]

SAN ANTONIO – Patients with stage T1a or T1b triple-negative breast cancer have an excellent prognosis even without chemotherapy, according to Dr. Eric P. Winer.

“There’s a perception on the part of many patients and physicians that all triple-negative breast cancer is bad, and that it’s destined to threaten and ultimately take a woman’s life. But even in an era where biology is king, stage still matters,” he observed at the San Antonio Breast Cancer Symposium.

He was a coinvestigator in a recent prospective cohort study which included 4,113 women with stage T1a or 1b breast cancer – that is, a tumor size no greater than 10 mm in its greatest dimension – without regional lymph node metastases or evidence of distant metastases. The patients, drawn from the National Comprehensive Cancer Network database, were treated in accord with institutional practice and followed for a median of 5.5 years.

Slightly over half of those in the subset with triple-negative breast cancer (TNBC) got chemotherapy. Those who received chemotherapy for T1a TNBC as defined by a tumor size not greater than 5 mm had a 5-year distant relapse-free survival (DRFS) of 100%, but the rate was still close to 95% in those not treated with chemotherapy. Outcomes were also quite favorable for patients with T1b TNBC who didn’t receive chemotherapy (J. Clin. Oncol. 2014;32:2142-50), said Dr. Winer, chief of the division of women’s cancers at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, Boston.

He noted that the findings in this study echo those of an earlier study by investigators at University of Texas M.D. Anderson Cancer Center, Houston, who reported a 5-year DRFS rate of 96% in 125 patients with T1a or 1b, lymph node-negative TNBC untreated with chemotherapy (J. Clin. Oncol. 2009;27:5700-6).

Dr. Winer said that while the consensus among most experts is that standard adjuvant chemotherapy regimens for patients with stage 2 or 3 TNBC include both anthracyclines and taxanes, his own view is that for patients with stage 1 TNBC “if you’re going to pursue chemotherapy, then treatment with a somewhat less toxic, shorter regimen would seem to be more appropriate.”

[email protected]

SAN ANTONIO – Oncologists are split over the use of platinum compounds as adjuvant or neoadjuvant therapy for triple-negative breast cancer patients, a rift likely to continue until definitive outcome data become available several years from now.

“In the U.S., I would say that about half of all medical oncologists are now in a fairly routine manner giving carboplatin in this setting,” Dr. Eric P. Winer estimated at the San Antonio Breast Cancer Symposium.

He’s not among them.

“Is carboplatin ready for prime time use in the adjuvant or neoadjuvant setting in triple-negative breast cancer? I personally feel we first need a definitive study showing improvement in disease-free survival and/or overall survival, or something close to that,” said Dr. Winer, chief of the division of women’s cancers at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, Boston.

Proponents of platinum salts cite two positive phase II randomized trials – GeparSixto and CALGB 40603 – which demonstrated significantly higher pathologic complete response (pCR) rates in patients with stage II or III triple-negative breast cancer (TNBC) with the addition of carboplatin to neoadjuvant chemotherapy.

The pro-platinum camp points to evidence suggesting a pCR in women with TNBC appears to be a good surrogate endpoint for event-free survival and overall survival, as shown in a recent meta-analysis by Dr. Patricia Cortazar of the Food and Drug Administration and her coworkers. The investigators concluded that pCR in response to neoadjuvant therapy with various regimens was associated with a 76% improvement in event-free survival and an 84% improvement in overall survival in 557 women with TNBC (Lancet 2014;384:164-72).

“The two phase II studies are going in the same direction,” observed Dr. Gunter von Minckwitz of the German Breast Group and principal investigator in the GeparSixto trial. “We have surveyed our group of investigators, and they are all using platinum in triple-negative breast cancer. The German guidelines say you can, but you don’t have to.”

But Dr. Winer, and by his estimate roughly half of all American medical oncologists, remain unconvinced.

“I think we should all keep in mind that pCR is a marker of better outcome, it’s not necessarily a required step in the process,” he said.

He’s leery of relying upon pCR as a surrogate endpoint in light of the deeply disappointing BEATRICE experience. The phase III BEATRICE trial included nearly 2,600 women with TNBC who were randomized to adjuvant chemotherapy alone or in combination with bevacizumab. The bevacizumab group had a higher pCR, but no improvement in disease-free survival or overall survival (Lancet Oncol. 2013;14:933-42).

“I would hate to see us all indiscriminately adding platinum to standard regimens, increasing toxicity, particularly if it is not associated with long-term benefit,” Dr. Winer said. “And even if it is associated with long-term benefit, I want to tease out who really benefits and which triple-negative patients are most sensitive to these agents.”

Progress is occurring in this area, he added. In GeparSixto, the addition of neoadjuvant carboplatin to paclitaxel and nonpegylated liposomal doxorubicin was associated with a 66.7% pCR rate in the subgroup of TNBC patients with a BRCA 1 or 2 germline mutation and a 43.5% rate in those without such mutations (Lancet Oncol. 2014;15:747-56).

Moreover, in the phase III Triple Negative Breast Cancer Trial (TNT) presented at this year’s San Antonio symposium, Dr. Andrew N.J. Tutt reported that in a prespecified analysis of the small subgroup comprising 43 BRCA mutation-positive patients, the objective response rate was 68% in those randomized to carboplatin, compared with 33% in those assigned to docetaxel. Moreover, mean progression-free survival was 6.8 months with carboplatin, significantly better than the 4.8 months with docetaxel or the 3.1 months in carboplatin-treated patients without a BRCA 1/2 mutation.

The TNT trial included 376 patients with metastatic or recurrent locally advanced TNBC randomized to single agent therapy. While the study provides no evidence of a superior response to carboplatin, compared with docetaxel in unselected patients with metastatic TNBC, it does support BRCA 1/2 mutation genotyping as part of decision making regarding therapy in metastatic TNBC and familial breast cancer, according to Dr. Tutt, professor of breast oncology at the Institute of Cancer Research, London.

The trial also tested the utility of Myriad Genetics’ novel Homologous Recombination Deficiency (HRD) score as a predictor of platinum-responsiveness of TNBC and concluded it was without benefit.

Dr. Winer noted that TNBC accounts for only about 15% of breast cancers. Still, that’s roughly 35,000 new cases per year in the United States alone – and TNBC is responsible for a disproportionate degree of breast cancer mortality.

“Perhaps in patients with BRCA 1 or 2 mutations, we’re getting close to thinking that platinum may be a standard, but even here I would await the completion of ongoing trials before we embrace that concept,” he said.

Among these studies is the 12-258 INFORM trial, a multicenter study in which 166 newly diagnosed breast cancer patients with BRCA1 or 2 mutations are being randomized to preoperative cisplatin or doxorubicin/cyclophosphamide.

Dr. William M. Sikov, principal investigator for the CALGB 40603 trial (J. Clin. Oncol. 2015;33:13-21), predicted there will be little crossover between the platinum-user and nonuser camps until definitive trials report whether the therapy improves relapse-free or overall survival.

“One group will say, ‘There’s an absolute increase in pathologic complete response with carboplatin in these two studies, and I’m convinced it’s a beneficial drug in these patients.’ It’s inexpensive, it’s available, although not approved for triple negative breast cancer, and it has some hematologic toxicities. But we have no long-term outcomes yet. I don’t think the TNT results will change anyone’s mind,” according to Dr. Sikov of Women and Infants Hospital in Providence, R.I.

Dr. Winer reported receiving research funding from Genentech. Dr. Sikov serves as a consultant to AbbVie and Celgene. Dr. Tutt reported having no financial conflicts.

[email protected]

SAN ANTONIO – Oncologists are split over the use of platinum compounds as adjuvant or neoadjuvant therapy for triple-negative breast cancer patients, a rift likely to continue until definitive outcome data become available several years from now.

“In the U.S., I would say that about half of all medical oncologists are now in a fairly routine manner giving carboplatin in this setting,” Dr. Eric P. Winer estimated at the San Antonio Breast Cancer Symposium.

He’s not among them.

“Is carboplatin ready for prime time use in the adjuvant or neoadjuvant setting in triple-negative breast cancer? I personally feel we first need a definitive study showing improvement in disease-free survival and/or overall survival, or something close to that,” said Dr. Winer, chief of the division of women’s cancers at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, Boston.

Proponents of platinum salts cite two positive phase II randomized trials – GeparSixto and CALGB 40603 – which demonstrated significantly higher pathologic complete response (pCR) rates in patients with stage II or III triple-negative breast cancer (TNBC) with the addition of carboplatin to neoadjuvant chemotherapy.

The pro-platinum camp points to evidence suggesting a pCR in women with TNBC appears to be a good surrogate endpoint for event-free survival and overall survival, as shown in a recent meta-analysis by Dr. Patricia Cortazar of the Food and Drug Administration and her coworkers. The investigators concluded that pCR in response to neoadjuvant therapy with various regimens was associated with a 76% improvement in event-free survival and an 84% improvement in overall survival in 557 women with TNBC (Lancet 2014;384:164-72).

“The two phase II studies are going in the same direction,” observed Dr. Gunter von Minckwitz of the German Breast Group and principal investigator in the GeparSixto trial. “We have surveyed our group of investigators, and they are all using platinum in triple-negative breast cancer. The German guidelines say you can, but you don’t have to.”

But Dr. Winer, and by his estimate roughly half of all American medical oncologists, remain unconvinced.

“I think we should all keep in mind that pCR is a marker of better outcome, it’s not necessarily a required step in the process,” he said.

He’s leery of relying upon pCR as a surrogate endpoint in light of the deeply disappointing BEATRICE experience. The phase III BEATRICE trial included nearly 2,600 women with TNBC who were randomized to adjuvant chemotherapy alone or in combination with bevacizumab. The bevacizumab group had a higher pCR, but no improvement in disease-free survival or overall survival (Lancet Oncol. 2013;14:933-42).

“I would hate to see us all indiscriminately adding platinum to standard regimens, increasing toxicity, particularly if it is not associated with long-term benefit,” Dr. Winer said. “And even if it is associated with long-term benefit, I want to tease out who really benefits and which triple-negative patients are most sensitive to these agents.”

Progress is occurring in this area, he added. In GeparSixto, the addition of neoadjuvant carboplatin to paclitaxel and nonpegylated liposomal doxorubicin was associated with a 66.7% pCR rate in the subgroup of TNBC patients with a BRCA 1 or 2 germline mutation and a 43.5% rate in those without such mutations (Lancet Oncol. 2014;15:747-56).

Moreover, in the phase III Triple Negative Breast Cancer Trial (TNT) presented at this year’s San Antonio symposium, Dr. Andrew N.J. Tutt reported that in a prespecified analysis of the small subgroup comprising 43 BRCA mutation-positive patients, the objective response rate was 68% in those randomized to carboplatin, compared with 33% in those assigned to docetaxel. Moreover, mean progression-free survival was 6.8 months with carboplatin, significantly better than the 4.8 months with docetaxel or the 3.1 months in carboplatin-treated patients without a BRCA 1/2 mutation.

The TNT trial included 376 patients with metastatic or recurrent locally advanced TNBC randomized to single agent therapy. While the study provides no evidence of a superior response to carboplatin, compared with docetaxel in unselected patients with metastatic TNBC, it does support BRCA 1/2 mutation genotyping as part of decision making regarding therapy in metastatic TNBC and familial breast cancer, according to Dr. Tutt, professor of breast oncology at the Institute of Cancer Research, London.

The trial also tested the utility of Myriad Genetics’ novel Homologous Recombination Deficiency (HRD) score as a predictor of platinum-responsiveness of TNBC and concluded it was without benefit.

Dr. Winer noted that TNBC accounts for only about 15% of breast cancers. Still, that’s roughly 35,000 new cases per year in the United States alone – and TNBC is responsible for a disproportionate degree of breast cancer mortality.

“Perhaps in patients with BRCA 1 or 2 mutations, we’re getting close to thinking that platinum may be a standard, but even here I would await the completion of ongoing trials before we embrace that concept,” he said.

Among these studies is the 12-258 INFORM trial, a multicenter study in which 166 newly diagnosed breast cancer patients with BRCA1 or 2 mutations are being randomized to preoperative cisplatin or doxorubicin/cyclophosphamide.

Dr. William M. Sikov, principal investigator for the CALGB 40603 trial (J. Clin. Oncol. 2015;33:13-21), predicted there will be little crossover between the platinum-user and nonuser camps until definitive trials report whether the therapy improves relapse-free or overall survival.

“One group will say, ‘There’s an absolute increase in pathologic complete response with carboplatin in these two studies, and I’m convinced it’s a beneficial drug in these patients.’ It’s inexpensive, it’s available, although not approved for triple negative breast cancer, and it has some hematologic toxicities. But we have no long-term outcomes yet. I don’t think the TNT results will change anyone’s mind,” according to Dr. Sikov of Women and Infants Hospital in Providence, R.I.

Dr. Winer reported receiving research funding from Genentech. Dr. Sikov serves as a consultant to AbbVie and Celgene. Dr. Tutt reported having no financial conflicts.

[email protected]

SAN ANTONIO – Oncologists are split over the use of platinum compounds as adjuvant or neoadjuvant therapy for triple-negative breast cancer patients, a rift likely to continue until definitive outcome data become available several years from now.

“In the U.S., I would say that about half of all medical oncologists are now in a fairly routine manner giving carboplatin in this setting,” Dr. Eric P. Winer estimated at the San Antonio Breast Cancer Symposium.

He’s not among them.

“Is carboplatin ready for prime time use in the adjuvant or neoadjuvant setting in triple-negative breast cancer? I personally feel we first need a definitive study showing improvement in disease-free survival and/or overall survival, or something close to that,” said Dr. Winer, chief of the division of women’s cancers at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, Boston.

Proponents of platinum salts cite two positive phase II randomized trials – GeparSixto and CALGB 40603 – which demonstrated significantly higher pathologic complete response (pCR) rates in patients with stage II or III triple-negative breast cancer (TNBC) with the addition of carboplatin to neoadjuvant chemotherapy.

The pro-platinum camp points to evidence suggesting a pCR in women with TNBC appears to be a good surrogate endpoint for event-free survival and overall survival, as shown in a recent meta-analysis by Dr. Patricia Cortazar of the Food and Drug Administration and her coworkers. The investigators concluded that pCR in response to neoadjuvant therapy with various regimens was associated with a 76% improvement in event-free survival and an 84% improvement in overall survival in 557 women with TNBC (Lancet 2014;384:164-72).

“The two phase II studies are going in the same direction,” observed Dr. Gunter von Minckwitz of the German Breast Group and principal investigator in the GeparSixto trial. “We have surveyed our group of investigators, and they are all using platinum in triple-negative breast cancer. The German guidelines say you can, but you don’t have to.”

But Dr. Winer, and by his estimate roughly half of all American medical oncologists, remain unconvinced.

“I think we should all keep in mind that pCR is a marker of better outcome, it’s not necessarily a required step in the process,” he said.

He’s leery of relying upon pCR as a surrogate endpoint in light of the deeply disappointing BEATRICE experience. The phase III BEATRICE trial included nearly 2,600 women with TNBC who were randomized to adjuvant chemotherapy alone or in combination with bevacizumab. The bevacizumab group had a higher pCR, but no improvement in disease-free survival or overall survival (Lancet Oncol. 2013;14:933-42).

“I would hate to see us all indiscriminately adding platinum to standard regimens, increasing toxicity, particularly if it is not associated with long-term benefit,” Dr. Winer said. “And even if it is associated with long-term benefit, I want to tease out who really benefits and which triple-negative patients are most sensitive to these agents.”

Progress is occurring in this area, he added. In GeparSixto, the addition of neoadjuvant carboplatin to paclitaxel and nonpegylated liposomal doxorubicin was associated with a 66.7% pCR rate in the subgroup of TNBC patients with a BRCA 1 or 2 germline mutation and a 43.5% rate in those without such mutations (Lancet Oncol. 2014;15:747-56).

Moreover, in the phase III Triple Negative Breast Cancer Trial (TNT) presented at this year’s San Antonio symposium, Dr. Andrew N.J. Tutt reported that in a prespecified analysis of the small subgroup comprising 43 BRCA mutation-positive patients, the objective response rate was 68% in those randomized to carboplatin, compared with 33% in those assigned to docetaxel. Moreover, mean progression-free survival was 6.8 months with carboplatin, significantly better than the 4.8 months with docetaxel or the 3.1 months in carboplatin-treated patients without a BRCA 1/2 mutation.

The TNT trial included 376 patients with metastatic or recurrent locally advanced TNBC randomized to single agent therapy. While the study provides no evidence of a superior response to carboplatin, compared with docetaxel in unselected patients with metastatic TNBC, it does support BRCA 1/2 mutation genotyping as part of decision making regarding therapy in metastatic TNBC and familial breast cancer, according to Dr. Tutt, professor of breast oncology at the Institute of Cancer Research, London.

The trial also tested the utility of Myriad Genetics’ novel Homologous Recombination Deficiency (HRD) score as a predictor of platinum-responsiveness of TNBC and concluded it was without benefit.

Dr. Winer noted that TNBC accounts for only about 15% of breast cancers. Still, that’s roughly 35,000 new cases per year in the United States alone – and TNBC is responsible for a disproportionate degree of breast cancer mortality.

“Perhaps in patients with BRCA 1 or 2 mutations, we’re getting close to thinking that platinum may be a standard, but even here I would await the completion of ongoing trials before we embrace that concept,” he said.

Among these studies is the 12-258 INFORM trial, a multicenter study in which 166 newly diagnosed breast cancer patients with BRCA1 or 2 mutations are being randomized to preoperative cisplatin or doxorubicin/cyclophosphamide.

Dr. William M. Sikov, principal investigator for the CALGB 40603 trial (J. Clin. Oncol. 2015;33:13-21), predicted there will be little crossover between the platinum-user and nonuser camps until definitive trials report whether the therapy improves relapse-free or overall survival.

“One group will say, ‘There’s an absolute increase in pathologic complete response with carboplatin in these two studies, and I’m convinced it’s a beneficial drug in these patients.’ It’s inexpensive, it’s available, although not approved for triple negative breast cancer, and it has some hematologic toxicities. But we have no long-term outcomes yet. I don’t think the TNT results will change anyone’s mind,” according to Dr. Sikov of Women and Infants Hospital in Providence, R.I.

Dr. Winer reported receiving research funding from Genentech. Dr. Sikov serves as a consultant to AbbVie and Celgene. Dr. Tutt reported having no financial conflicts.

[email protected]

SAN ANTONIO – Hypertension, dyslipidemia, and type 2 diabetes are common among breast cancer survivors – and so is nonadherence to medications prescribed for these major comorbid conditions.

That was the central finding from COMBO (Commonly Used Medications and Breast Cancer Outcomes), a retrospective cohort study of 4,216 breast cancer survivors belonging to Group Health Cooperative, Gregory S. Calip, Pharm.D., reported at the San Antonio Breast Cancer Symposium.

“This is the first study to investigate breast cancer characteristics and treatments in relation to nonadherence to chronic medications for hypertension, diabetes, and dyslipidemia,” said Dr. Calip of the University of Illinois, Chicago. “Our results suggest that some breast cancer treatments may be associated with nonadherence to antihypertensive agents and oral diabetes medications, but not statins. These findings highlight possible opportunities to improve comorbid condition care in the growing population of breast cancer survivors.”

The irony is that while experiencing breast cancer understandably renders survivors deeply concerned about the prospect of cancer-related death, by not taking their medications for these common comorbid conditions these women increase their overall mortality risk, and particularly their risk of death due to cardiovascular disease and stroke.

The women in the COMBO study had been diagnosed with stage I or II breast cancer during 1990-2008 and did not experience recurrence or a second primary breast cancer during their second year after breast cancer diagnosis. Their medication adherence during that second year was measured via automated health plan pharmacy dispensing records. Patients were classified as nonadherent if their medication possession ratio, or MPR, was less than 0.8.

Antihypertensive agents were prescribed for 1,929 of the subjects, statins for 1,072, and oral diabetes drugs for 449.

During days 366-730 post breast cancer diagnosis, 37% of the women were nonadherent to antihypertensive medications, 39% to prescribed statins, and 75% to their oral diabetes medications.

Common forms of breast cancer therapy were independently associated with increased likelihood of nonadherence in multivariate logistic regression analysis. For example, chemotherapy was associated with a 67% increased likelihood of nonadherence to diabetes medications during year 2 after breast cancer diagnosis. Patients who received radiation therapy or hormonal therapy were, respectively, 21% and 25% more likely to be nonadherent to antihypertensive therapy.

One factor associated with increased likelihood of adherence to medications for comorbid conditions was greater contact with a primary care physician. Breast cancer survivors who saw their primary care physicians two or more times during year 2 post diagnosis were 70% less likely to be nonadherent to antihypertensive therapy than were those who visited their primary care physicians less frequently.

Greater body mass index was associated with significantly less likelihood of nonadherence to antihypertensive agents but not statins or diabetes medications. When researchers used a BMI below 25 kg/m² for reference, patients with a BMI of 25-29.9 were 39% less likely to be nonadherent to antihypertensive therapy, those with a BMI of 30-34.9 kg/m² were 46% less likely, and women with a BMI of 35 kg/m² or greater were 63% less likely to be nonadherent to their antihypertensive therapy.

A higher Charlson comorbidity score of 2 or more during the first year following breast cancer diagnosis was associated with a 51% reduction in likelihood of nonadherence to diabetes medications during year 2 and a 46% lower nonadherence rate for statins than in patients with a Charlson score below 2.

As reported in previous studies of non-cancer patients, younger age was associated with increased nonadherence. This was true across the board for all three medication classes, although the age effect was most dramatic with respect to nonadherence to statins and oral diabetes medications. Fifty- to 54-year-olds were 3.4- and 1.8-fold more likely than were women age 65 or older to be nonadherent to diabetes drugs and statins, respectively, while breast cancer survivors under age 50 were 7.1- and 2.8-fold more likely to be nonadherent to those types of medications.

Discussant Dawn L. Hershman called the COMBO study medication nonadherence rates “pretty awful.” And if breast cancer survivors aren’t taking their medications for chronic comorbid conditions, it’s not much of a leap to think they may not be adherent to their breast cancer–related medications, she said. She urged her fellow breast cancer specialists to think beyond their specialty focus, consider the patient as a whole, and do what they can to promote adherence to medications targeting these potentially serious comorbidities.

“So, what can we do? We can try to engage technology,” said Dr. Hershman, a medical oncologist at Columbia University, New York.

She cited a randomized, controlled trial by other investigators which showed that automated phone calls reminding patients to take their cardiovascular medications had a salutary effect. In addition, she was an investigator in a large study of text messaging as an effective tool for improving adherence to hormonal therapy.

The COMBO study was supported by the National Cancer Institute and the University of Washington, Seattle. Dr. Calip reported having no financial conflicts.

[email protected]

SAN ANTONIO – Hypertension, dyslipidemia, and type 2 diabetes are common among breast cancer survivors – and so is nonadherence to medications prescribed for these major comorbid conditions.

That was the central finding from COMBO (Commonly Used Medications and Breast Cancer Outcomes), a retrospective cohort study of 4,216 breast cancer survivors belonging to Group Health Cooperative, Gregory S. Calip, Pharm.D., reported at the San Antonio Breast Cancer Symposium.

“This is the first study to investigate breast cancer characteristics and treatments in relation to nonadherence to chronic medications for hypertension, diabetes, and dyslipidemia,” said Dr. Calip of the University of Illinois, Chicago. “Our results suggest that some breast cancer treatments may be associated with nonadherence to antihypertensive agents and oral diabetes medications, but not statins. These findings highlight possible opportunities to improve comorbid condition care in the growing population of breast cancer survivors.”

The irony is that while experiencing breast cancer understandably renders survivors deeply concerned about the prospect of cancer-related death, by not taking their medications for these common comorbid conditions these women increase their overall mortality risk, and particularly their risk of death due to cardiovascular disease and stroke.

The women in the COMBO study had been diagnosed with stage I or II breast cancer during 1990-2008 and did not experience recurrence or a second primary breast cancer during their second year after breast cancer diagnosis. Their medication adherence during that second year was measured via automated health plan pharmacy dispensing records. Patients were classified as nonadherent if their medication possession ratio, or MPR, was less than 0.8.

Antihypertensive agents were prescribed for 1,929 of the subjects, statins for 1,072, and oral diabetes drugs for 449.

During days 366-730 post breast cancer diagnosis, 37% of the women were nonadherent to antihypertensive medications, 39% to prescribed statins, and 75% to their oral diabetes medications.

Common forms of breast cancer therapy were independently associated with increased likelihood of nonadherence in multivariate logistic regression analysis. For example, chemotherapy was associated with a 67% increased likelihood of nonadherence to diabetes medications during year 2 after breast cancer diagnosis. Patients who received radiation therapy or hormonal therapy were, respectively, 21% and 25% more likely to be nonadherent to antihypertensive therapy.

One factor associated with increased likelihood of adherence to medications for comorbid conditions was greater contact with a primary care physician. Breast cancer survivors who saw their primary care physicians two or more times during year 2 post diagnosis were 70% less likely to be nonadherent to antihypertensive therapy than were those who visited their primary care physicians less frequently.

Greater body mass index was associated with significantly less likelihood of nonadherence to antihypertensive agents but not statins or diabetes medications. When researchers used a BMI below 25 kg/m² for reference, patients with a BMI of 25-29.9 were 39% less likely to be nonadherent to antihypertensive therapy, those with a BMI of 30-34.9 kg/m² were 46% less likely, and women with a BMI of 35 kg/m² or greater were 63% less likely to be nonadherent to their antihypertensive therapy.

A higher Charlson comorbidity score of 2 or more during the first year following breast cancer diagnosis was associated with a 51% reduction in likelihood of nonadherence to diabetes medications during year 2 and a 46% lower nonadherence rate for statins than in patients with a Charlson score below 2.

As reported in previous studies of non-cancer patients, younger age was associated with increased nonadherence. This was true across the board for all three medication classes, although the age effect was most dramatic with respect to nonadherence to statins and oral diabetes medications. Fifty- to 54-year-olds were 3.4- and 1.8-fold more likely than were women age 65 or older to be nonadherent to diabetes drugs and statins, respectively, while breast cancer survivors under age 50 were 7.1- and 2.8-fold more likely to be nonadherent to those types of medications.

Discussant Dawn L. Hershman called the COMBO study medication nonadherence rates “pretty awful.” And if breast cancer survivors aren’t taking their medications for chronic comorbid conditions, it’s not much of a leap to think they may not be adherent to their breast cancer–related medications, she said. She urged her fellow breast cancer specialists to think beyond their specialty focus, consider the patient as a whole, and do what they can to promote adherence to medications targeting these potentially serious comorbidities.

“So, what can we do? We can try to engage technology,” said Dr. Hershman, a medical oncologist at Columbia University, New York.

She cited a randomized, controlled trial by other investigators which showed that automated phone calls reminding patients to take their cardiovascular medications had a salutary effect. In addition, she was an investigator in a large study of text messaging as an effective tool for improving adherence to hormonal therapy.

The COMBO study was supported by the National Cancer Institute and the University of Washington, Seattle. Dr. Calip reported having no financial conflicts.

[email protected]

SAN ANTONIO – Hypertension, dyslipidemia, and type 2 diabetes are common among breast cancer survivors – and so is nonadherence to medications prescribed for these major comorbid conditions.

That was the central finding from COMBO (Commonly Used Medications and Breast Cancer Outcomes), a retrospective cohort study of 4,216 breast cancer survivors belonging to Group Health Cooperative, Gregory S. Calip, Pharm.D., reported at the San Antonio Breast Cancer Symposium.

“This is the first study to investigate breast cancer characteristics and treatments in relation to nonadherence to chronic medications for hypertension, diabetes, and dyslipidemia,” said Dr. Calip of the University of Illinois, Chicago. “Our results suggest that some breast cancer treatments may be associated with nonadherence to antihypertensive agents and oral diabetes medications, but not statins. These findings highlight possible opportunities to improve comorbid condition care in the growing population of breast cancer survivors.”

The irony is that while experiencing breast cancer understandably renders survivors deeply concerned about the prospect of cancer-related death, by not taking their medications for these common comorbid conditions these women increase their overall mortality risk, and particularly their risk of death due to cardiovascular disease and stroke.

The women in the COMBO study had been diagnosed with stage I or II breast cancer during 1990-2008 and did not experience recurrence or a second primary breast cancer during their second year after breast cancer diagnosis. Their medication adherence during that second year was measured via automated health plan pharmacy dispensing records. Patients were classified as nonadherent if their medication possession ratio, or MPR, was less than 0.8.

Antihypertensive agents were prescribed for 1,929 of the subjects, statins for 1,072, and oral diabetes drugs for 449.

During days 366-730 post breast cancer diagnosis, 37% of the women were nonadherent to antihypertensive medications, 39% to prescribed statins, and 75% to their oral diabetes medications.

Common forms of breast cancer therapy were independently associated with increased likelihood of nonadherence in multivariate logistic regression analysis. For example, chemotherapy was associated with a 67% increased likelihood of nonadherence to diabetes medications during year 2 after breast cancer diagnosis. Patients who received radiation therapy or hormonal therapy were, respectively, 21% and 25% more likely to be nonadherent to antihypertensive therapy.

One factor associated with increased likelihood of adherence to medications for comorbid conditions was greater contact with a primary care physician. Breast cancer survivors who saw their primary care physicians two or more times during year 2 post diagnosis were 70% less likely to be nonadherent to antihypertensive therapy than were those who visited their primary care physicians less frequently.

Greater body mass index was associated with significantly less likelihood of nonadherence to antihypertensive agents but not statins or diabetes medications. When researchers used a BMI below 25 kg/m² for reference, patients with a BMI of 25-29.9 were 39% less likely to be nonadherent to antihypertensive therapy, those with a BMI of 30-34.9 kg/m² were 46% less likely, and women with a BMI of 35 kg/m² or greater were 63% less likely to be nonadherent to their antihypertensive therapy.

A higher Charlson comorbidity score of 2 or more during the first year following breast cancer diagnosis was associated with a 51% reduction in likelihood of nonadherence to diabetes medications during year 2 and a 46% lower nonadherence rate for statins than in patients with a Charlson score below 2.

As reported in previous studies of non-cancer patients, younger age was associated with increased nonadherence. This was true across the board for all three medication classes, although the age effect was most dramatic with respect to nonadherence to statins and oral diabetes medications. Fifty- to 54-year-olds were 3.4- and 1.8-fold more likely than were women age 65 or older to be nonadherent to diabetes drugs and statins, respectively, while breast cancer survivors under age 50 were 7.1- and 2.8-fold more likely to be nonadherent to those types of medications.

Discussant Dawn L. Hershman called the COMBO study medication nonadherence rates “pretty awful.” And if breast cancer survivors aren’t taking their medications for chronic comorbid conditions, it’s not much of a leap to think they may not be adherent to their breast cancer–related medications, she said. She urged her fellow breast cancer specialists to think beyond their specialty focus, consider the patient as a whole, and do what they can to promote adherence to medications targeting these potentially serious comorbidities.

“So, what can we do? We can try to engage technology,” said Dr. Hershman, a medical oncologist at Columbia University, New York.

She cited a randomized, controlled trial by other investigators which showed that automated phone calls reminding patients to take their cardiovascular medications had a salutary effect. In addition, she was an investigator in a large study of text messaging as an effective tool for improving adherence to hormonal therapy.

The COMBO study was supported by the National Cancer Institute and the University of Washington, Seattle. Dr. Calip reported having no financial conflicts.

[email protected]

SAN ANTONIO – Low-level laser therapy proved highly effective in managing chemotherapy-induced oral mucositis in a retrospective study.

Although this was the first study of low-level laser therapy in breast cancer patients, this form of therapy is already widely used to prevent and treat oral mucositis in hematopoietic stem cell transplant recipients as well as in patients with head and neck cancer. These preliminary findings in a breast cancer population warrant confirmation in a randomized controlled trial, Sandrine Censabella, Ph.D., said at the San Antonio Breast Cancer Symposium.

Roughly 40% of patients develop oral mucositis as a consequence of standard-dose chemotherapy. Oral mucositis is the most debilitating, severe, and costly nonhematologic complication of oncologic therapy. It compromises both quality of life and treatment outcomes, said Dr. Censabella of Jessa Hospital in Hasselt, Belgium.

She reported on 93 patients with stage 0-IV breast cancer and chemotherapy-induced oral mucositis who received low-level laser therapy using a gallium arsenide laser at 665-nm wavelength and 100 mW of output power combined with a continuous-emission infrared laser with an output power of 500 mW. The laser energy, 4 J per application point, was delivered via a 600-mcm optical fiber.

The treatment schedule was two sessions per week until lesion healing occurred. Depending on the extent of the oral mucositis, up to seven oral sites could be treated: lips, tongue, palate, inside of the two cheeks, tonsils, and mouth floor.

Outcomes were assessed in a standardized fashion by trained nurses using the World Health Organization 0-4 grading scale, where 0 means unaffected, 1 represents soreness and erythema, 2 means erythema and ulcers but with an ability to eat solid foods, 3 is for patients with ulcers who require a liquid diet only, and 4 is for patients incapable of oral nutritional intake. In addition, investigators calculated an oral mucositis score for every patient by adding up the WHO grades at all affected sites.

Laser therapy began a mean of 49 days after the start of chemotherapy, which was anthracycline based in two-thirds of cases. The mean age of the women was 54.8 years.

Subjects received a mean of 5.7 laser treatment sessions, during which they showed a significant reduction in oral mucositis severity. At baseline, 60% of patients had WHO grade 2 lesions, a rate that dropped to 30% at the end of treatment several weeks later. While only 12% of patients were WHO grade 1 at baseline, 65% were at the conclusion of the laser treatment program. Twenty-eight percent of women were WHO grade 3 at entry, compared with just 5.4% after laser treatment.

The mean baseline combined oral mucositis score averaged 6.6, improving to 2.78 at treatment’s end.

Self-reported pain scores improved from 5.14 at baseline on a 10-point scale to 1.64 at the conclusion of laser therapy.

At the end of laser therapy, only 2% had a worse WHO grade than at baseline, 8.6% had a worse composite oral mucositis score, and no one reported more pain than at entry.

“These findings are the first to document a beneficial effect of low-level laser therapy in a large group of breast cancer patients and suggest that low-level laser therapy might become a standard management for oral mucositis in all cancer patients,” Dr. Censabella said.

She reported having no financial conflicts regarding this study.

[email protected]

SAN ANTONIO – Low-level laser therapy proved highly effective in managing chemotherapy-induced oral mucositis in a retrospective study.

Although this was the first study of low-level laser therapy in breast cancer patients, this form of therapy is already widely used to prevent and treat oral mucositis in hematopoietic stem cell transplant recipients as well as in patients with head and neck cancer. These preliminary findings in a breast cancer population warrant confirmation in a randomized controlled trial, Sandrine Censabella, Ph.D., said at the San Antonio Breast Cancer Symposium.

Roughly 40% of patients develop oral mucositis as a consequence of standard-dose chemotherapy. Oral mucositis is the most debilitating, severe, and costly nonhematologic complication of oncologic therapy. It compromises both quality of life and treatment outcomes, said Dr. Censabella of Jessa Hospital in Hasselt, Belgium.

She reported on 93 patients with stage 0-IV breast cancer and chemotherapy-induced oral mucositis who received low-level laser therapy using a gallium arsenide laser at 665-nm wavelength and 100 mW of output power combined with a continuous-emission infrared laser with an output power of 500 mW. The laser energy, 4 J per application point, was delivered via a 600-mcm optical fiber.

The treatment schedule was two sessions per week until lesion healing occurred. Depending on the extent of the oral mucositis, up to seven oral sites could be treated: lips, tongue, palate, inside of the two cheeks, tonsils, and mouth floor.

Outcomes were assessed in a standardized fashion by trained nurses using the World Health Organization 0-4 grading scale, where 0 means unaffected, 1 represents soreness and erythema, 2 means erythema and ulcers but with an ability to eat solid foods, 3 is for patients with ulcers who require a liquid diet only, and 4 is for patients incapable of oral nutritional intake. In addition, investigators calculated an oral mucositis score for every patient by adding up the WHO grades at all affected sites.

Laser therapy began a mean of 49 days after the start of chemotherapy, which was anthracycline based in two-thirds of cases. The mean age of the women was 54.8 years.

Subjects received a mean of 5.7 laser treatment sessions, during which they showed a significant reduction in oral mucositis severity. At baseline, 60% of patients had WHO grade 2 lesions, a rate that dropped to 30% at the end of treatment several weeks later. While only 12% of patients were WHO grade 1 at baseline, 65% were at the conclusion of the laser treatment program. Twenty-eight percent of women were WHO grade 3 at entry, compared with just 5.4% after laser treatment.

The mean baseline combined oral mucositis score averaged 6.6, improving to 2.78 at treatment’s end.

Self-reported pain scores improved from 5.14 at baseline on a 10-point scale to 1.64 at the conclusion of laser therapy.

At the end of laser therapy, only 2% had a worse WHO grade than at baseline, 8.6% had a worse composite oral mucositis score, and no one reported more pain than at entry.

“These findings are the first to document a beneficial effect of low-level laser therapy in a large group of breast cancer patients and suggest that low-level laser therapy might become a standard management for oral mucositis in all cancer patients,” Dr. Censabella said.

She reported having no financial conflicts regarding this study.

[email protected]

SAN ANTONIO – Low-level laser therapy proved highly effective in managing chemotherapy-induced oral mucositis in a retrospective study.

Although this was the first study of low-level laser therapy in breast cancer patients, this form of therapy is already widely used to prevent and treat oral mucositis in hematopoietic stem cell transplant recipients as well as in patients with head and neck cancer. These preliminary findings in a breast cancer population warrant confirmation in a randomized controlled trial, Sandrine Censabella, Ph.D., said at the San Antonio Breast Cancer Symposium.

Roughly 40% of patients develop oral mucositis as a consequence of standard-dose chemotherapy. Oral mucositis is the most debilitating, severe, and costly nonhematologic complication of oncologic therapy. It compromises both quality of life and treatment outcomes, said Dr. Censabella of Jessa Hospital in Hasselt, Belgium.

She reported on 93 patients with stage 0-IV breast cancer and chemotherapy-induced oral mucositis who received low-level laser therapy using a gallium arsenide laser at 665-nm wavelength and 100 mW of output power combined with a continuous-emission infrared laser with an output power of 500 mW. The laser energy, 4 J per application point, was delivered via a 600-mcm optical fiber.

The treatment schedule was two sessions per week until lesion healing occurred. Depending on the extent of the oral mucositis, up to seven oral sites could be treated: lips, tongue, palate, inside of the two cheeks, tonsils, and mouth floor.

Outcomes were assessed in a standardized fashion by trained nurses using the World Health Organization 0-4 grading scale, where 0 means unaffected, 1 represents soreness and erythema, 2 means erythema and ulcers but with an ability to eat solid foods, 3 is for patients with ulcers who require a liquid diet only, and 4 is for patients incapable of oral nutritional intake. In addition, investigators calculated an oral mucositis score for every patient by adding up the WHO grades at all affected sites.

Laser therapy began a mean of 49 days after the start of chemotherapy, which was anthracycline based in two-thirds of cases. The mean age of the women was 54.8 years.

Subjects received a mean of 5.7 laser treatment sessions, during which they showed a significant reduction in oral mucositis severity. At baseline, 60% of patients had WHO grade 2 lesions, a rate that dropped to 30% at the end of treatment several weeks later. While only 12% of patients were WHO grade 1 at baseline, 65% were at the conclusion of the laser treatment program. Twenty-eight percent of women were WHO grade 3 at entry, compared with just 5.4% after laser treatment.

The mean baseline combined oral mucositis score averaged 6.6, improving to 2.78 at treatment’s end.

Self-reported pain scores improved from 5.14 at baseline on a 10-point scale to 1.64 at the conclusion of laser therapy.

At the end of laser therapy, only 2% had a worse WHO grade than at baseline, 8.6% had a worse composite oral mucositis score, and no one reported more pain than at entry.

“These findings are the first to document a beneficial effect of low-level laser therapy in a large group of breast cancer patients and suggest that low-level laser therapy might become a standard management for oral mucositis in all cancer patients,” Dr. Censabella said.

She reported having no financial conflicts regarding this study.

[email protected]

SAN ANTONIO – Breast cancer patients are often advised that in order to avoid developing lymphedema they should shun blood pressure cuffs, injections, and blood draws on their at-risk arm as well as airplane travel unless wearing a compression sleeve.

All these recommendations are anecdotally based. None withstood formal evaluation in a prospective study of 710 breast cancer patients with 860 treated and thus potentially at-risk breasts, Chantal M. Ferguson reported at the San Antonio Breast Cancer Symposium.

“Our findings don’t support current guidelines regarding these activities and suggest that further studies are needed to determine if these guidelines are appropriate,” said Ms. Ferguson of Massachusetts General Hospital, Boston.

Standard practice for newly diagnosed breast cancer patients at Mass. General is to enter into a prospective screening program for lymphedema, a chronic, painful swelling caused by damage to the lymphatic system secondary to breast cancer therapy.

Breast cancer patients routinely have bilateral arm volume measurements taken using a perometer preoperatively, postoperatively, after finishing chemotherapy and radiotherapy, and at 3- to 7-month intervals thereafter following completion of treatment. At each measurement, data are collected on exposures to airplane flights, blood pressure readings, and the other often-cited putative risk factors.

The incidence of lymphedema among the 710 patients in the study at 24 months was 7.05%. The diagnosis required at least a 10% increase in arm volume, compared with the untreated side. For women who underwent bilateral breast surgery, a weight-adjusted volume change formula was employed.

Consistent with the medical literature, axial lymph node dissection and a higher preoperative body mass index were significantly associated with the development of lymphedema. So was self-reported trauma to the at-risk arm, although the reported trauma ranged in severity from bruises to fractures in motor vehicle accidents.

Session cochair Dr. Michelle E. Melisko observed that few medical oncologists are well informed about lymphedema or the numerous and highly complex functions of the lymphatic system, so she was favorably impressed that physicians at Mass. General have incorporated structured screening for the disorder as part of the institutional standard of care.

She cautioned, however, that rates of the risk factor events under study were relatively low. For example, only 17% of the breast cancer patients had one or more blood pressure measurements taken on their at-risk arm during 2 years of prospective follow-up, 9% had one or more blood draws, and 15% of patients flew for a total of 12 hours or more.

“I’m not sure that we can take these data to say we can let patients go hog wild and get their blood pressure measured all the time on that arm. This is a large prospective trial featuring a broad range of patient ages and BMIs, and both lumpectomy and mastectomy patients, and the trial adds a lot to the literature, but it does need to be interpreted with caution,” said Dr. Melisko of the University of California, San Francisco.

The study was funded by the National Cancer Institute and the Adele McKinnon Research Fund for Breast Cancer–related Lymphedema. Ms. Ferguson reported having no financial conflicts.

[email protected]

SAN ANTONIO – Breast cancer patients are often advised that in order to avoid developing lymphedema they should shun blood pressure cuffs, injections, and blood draws on their at-risk arm as well as airplane travel unless wearing a compression sleeve.

All these recommendations are anecdotally based. None withstood formal evaluation in a prospective study of 710 breast cancer patients with 860 treated and thus potentially at-risk breasts, Chantal M. Ferguson reported at the San Antonio Breast Cancer Symposium.

“Our findings don’t support current guidelines regarding these activities and suggest that further studies are needed to determine if these guidelines are appropriate,” said Ms. Ferguson of Massachusetts General Hospital, Boston.

Standard practice for newly diagnosed breast cancer patients at Mass. General is to enter into a prospective screening program for lymphedema, a chronic, painful swelling caused by damage to the lymphatic system secondary to breast cancer therapy.

Breast cancer patients routinely have bilateral arm volume measurements taken using a perometer preoperatively, postoperatively, after finishing chemotherapy and radiotherapy, and at 3- to 7-month intervals thereafter following completion of treatment. At each measurement, data are collected on exposures to airplane flights, blood pressure readings, and the other often-cited putative risk factors.

The incidence of lymphedema among the 710 patients in the study at 24 months was 7.05%. The diagnosis required at least a 10% increase in arm volume, compared with the untreated side. For women who underwent bilateral breast surgery, a weight-adjusted volume change formula was employed.

Consistent with the medical literature, axial lymph node dissection and a higher preoperative body mass index were significantly associated with the development of lymphedema. So was self-reported trauma to the at-risk arm, although the reported trauma ranged in severity from bruises to fractures in motor vehicle accidents.

Session cochair Dr. Michelle E. Melisko observed that few medical oncologists are well informed about lymphedema or the numerous and highly complex functions of the lymphatic system, so she was favorably impressed that physicians at Mass. General have incorporated structured screening for the disorder as part of the institutional standard of care.

She cautioned, however, that rates of the risk factor events under study were relatively low. For example, only 17% of the breast cancer patients had one or more blood pressure measurements taken on their at-risk arm during 2 years of prospective follow-up, 9% had one or more blood draws, and 15% of patients flew for a total of 12 hours or more.

“I’m not sure that we can take these data to say we can let patients go hog wild and get their blood pressure measured all the time on that arm. This is a large prospective trial featuring a broad range of patient ages and BMIs, and both lumpectomy and mastectomy patients, and the trial adds a lot to the literature, but it does need to be interpreted with caution,” said Dr. Melisko of the University of California, San Francisco.

The study was funded by the National Cancer Institute and the Adele McKinnon Research Fund for Breast Cancer–related Lymphedema. Ms. Ferguson reported having no financial conflicts.

[email protected]

SAN ANTONIO – Breast cancer patients are often advised that in order to avoid developing lymphedema they should shun blood pressure cuffs, injections, and blood draws on their at-risk arm as well as airplane travel unless wearing a compression sleeve.

All these recommendations are anecdotally based. None withstood formal evaluation in a prospective study of 710 breast cancer patients with 860 treated and thus potentially at-risk breasts, Chantal M. Ferguson reported at the San Antonio Breast Cancer Symposium.

“Our findings don’t support current guidelines regarding these activities and suggest that further studies are needed to determine if these guidelines are appropriate,” said Ms. Ferguson of Massachusetts General Hospital, Boston.

Standard practice for newly diagnosed breast cancer patients at Mass. General is to enter into a prospective screening program for lymphedema, a chronic, painful swelling caused by damage to the lymphatic system secondary to breast cancer therapy.

Breast cancer patients routinely have bilateral arm volume measurements taken using a perometer preoperatively, postoperatively, after finishing chemotherapy and radiotherapy, and at 3- to 7-month intervals thereafter following completion of treatment. At each measurement, data are collected on exposures to airplane flights, blood pressure readings, and the other often-cited putative risk factors.

The incidence of lymphedema among the 710 patients in the study at 24 months was 7.05%. The diagnosis required at least a 10% increase in arm volume, compared with the untreated side. For women who underwent bilateral breast surgery, a weight-adjusted volume change formula was employed.

Consistent with the medical literature, axial lymph node dissection and a higher preoperative body mass index were significantly associated with the development of lymphedema. So was self-reported trauma to the at-risk arm, although the reported trauma ranged in severity from bruises to fractures in motor vehicle accidents.

Session cochair Dr. Michelle E. Melisko observed that few medical oncologists are well informed about lymphedema or the numerous and highly complex functions of the lymphatic system, so she was favorably impressed that physicians at Mass. General have incorporated structured screening for the disorder as part of the institutional standard of care.

She cautioned, however, that rates of the risk factor events under study were relatively low. For example, only 17% of the breast cancer patients had one or more blood pressure measurements taken on their at-risk arm during 2 years of prospective follow-up, 9% had one or more blood draws, and 15% of patients flew for a total of 12 hours or more.

“I’m not sure that we can take these data to say we can let patients go hog wild and get their blood pressure measured all the time on that arm. This is a large prospective trial featuring a broad range of patient ages and BMIs, and both lumpectomy and mastectomy patients, and the trial adds a lot to the literature, but it does need to be interpreted with caution,” said Dr. Melisko of the University of California, San Francisco.

The study was funded by the National Cancer Institute and the Adele McKinnon Research Fund for Breast Cancer–related Lymphedema. Ms. Ferguson reported having no financial conflicts.

[email protected]

SAN ANTONIO – Adjuvant aromatase inhibitor therapy in postmenopausal breast cancer survivors was associated with an increased risk of incident nonischemic cardiovascular disease, compared with tamoxifen users in a large prospective study conducted at Kaiser Permanente.

The elevation in risk was comparable in women on aromatase inhibitors (AIs) only and in those who used sequential tamoxifen followed by an AI, Reina Haque, Ph.D., reported at the San Antonio Breast Cancer Symposium.

She presented a prospective cohort study of 13,273 postmenopausal women free of known cardiovascular disease at the time of their breast cancer diagnosis during 1991-2010. Thirty-two percent of them used adjuvant tamoxifen only, 29% used an aromatase inhibitor (AI) only, 20% switched from adjuvant tamoxifen to an AI, and the rest used neither endocrine therapy.

Bruce Jancin/Frontline Medical News

During a mean of 5.5 and maximum 22 years of prospective follow-up, 3,711 women experienced their first cardiovascular disease event. Neither rates of ischemic heart disease nor stroke differed significantly among the groups on tamoxifen, AIs, both in sequence, or neither. However, those on adjuvant AI therapy had an adjusted 26% greater risk of ‘other’ cardiovascular disease, compared with women on tamoxifen only.

The category of ‘other’ cardiovascular disease was comprised of heart failure, arrhythmia, cardiomyopathy, pericarditis, and valvular dysfunction, explained Dr. Haque, a research scientist at Kaiser Permanente of Southern California, Pasadena.

Similarly, women who switched from tamoxifen to an AI were at 28% greater risk of developing ‘other’ cardiovascular disease, compared with those on tamoxifen alone in a multivariate Cox analysis adjusted for age, demographics, comorbid conditions, cancer treatment, tumor characteristics, and use of antihypertensive agents and other cardiovascular medications.

In the subset of 7,982 patients who underwent breast irradiation, those on an adjuvant AI who received left-sided breast radiation therapy were at an adjusted 21% increased risk of all forms of cardiovascular disease – ischemic as well as other – compared with those who got left-sided breast irradiation and took tamoxifen.

As this was an observational study, the results warrant cautious interpretation, Dr. Haque said. Nevertheless, this is a study based upon 72,886 women-years of prospective follow-up and a large number of cardiovascular events, she noted.

The study was funded by the California Breast Cancer Research Program and the National Cancer Institute. Dr. Haque reported having no financial conflicts.

[email protected]

SAN ANTONIO – Adjuvant aromatase inhibitor therapy in postmenopausal breast cancer survivors was associated with an increased risk of incident nonischemic cardiovascular disease, compared with tamoxifen users in a large prospective study conducted at Kaiser Permanente.

The elevation in risk was comparable in women on aromatase inhibitors (AIs) only and in those who used sequential tamoxifen followed by an AI, Reina Haque, Ph.D., reported at the San Antonio Breast Cancer Symposium.

She presented a prospective cohort study of 13,273 postmenopausal women free of known cardiovascular disease at the time of their breast cancer diagnosis during 1991-2010. Thirty-two percent of them used adjuvant tamoxifen only, 29% used an aromatase inhibitor (AI) only, 20% switched from adjuvant tamoxifen to an AI, and the rest used neither endocrine therapy.

Bruce Jancin/Frontline Medical News

During a mean of 5.5 and maximum 22 years of prospective follow-up, 3,711 women experienced their first cardiovascular disease event. Neither rates of ischemic heart disease nor stroke differed significantly among the groups on tamoxifen, AIs, both in sequence, or neither. However, those on adjuvant AI therapy had an adjusted 26% greater risk of ‘other’ cardiovascular disease, compared with women on tamoxifen only.

The category of ‘other’ cardiovascular disease was comprised of heart failure, arrhythmia, cardiomyopathy, pericarditis, and valvular dysfunction, explained Dr. Haque, a research scientist at Kaiser Permanente of Southern California, Pasadena.

Similarly, women who switched from tamoxifen to an AI were at 28% greater risk of developing ‘other’ cardiovascular disease, compared with those on tamoxifen alone in a multivariate Cox analysis adjusted for age, demographics, comorbid conditions, cancer treatment, tumor characteristics, and use of antihypertensive agents and other cardiovascular medications.

In the subset of 7,982 patients who underwent breast irradiation, those on an adjuvant AI who received left-sided breast radiation therapy were at an adjusted 21% increased risk of all forms of cardiovascular disease – ischemic as well as other – compared with those who got left-sided breast irradiation and took tamoxifen.

As this was an observational study, the results warrant cautious interpretation, Dr. Haque said. Nevertheless, this is a study based upon 72,886 women-years of prospective follow-up and a large number of cardiovascular events, she noted.

The study was funded by the California Breast Cancer Research Program and the National Cancer Institute. Dr. Haque reported having no financial conflicts.

[email protected]

SAN ANTONIO – Adjuvant aromatase inhibitor therapy in postmenopausal breast cancer survivors was associated with an increased risk of incident nonischemic cardiovascular disease, compared with tamoxifen users in a large prospective study conducted at Kaiser Permanente.

The elevation in risk was comparable in women on aromatase inhibitors (AIs) only and in those who used sequential tamoxifen followed by an AI, Reina Haque, Ph.D., reported at the San Antonio Breast Cancer Symposium.

She presented a prospective cohort study of 13,273 postmenopausal women free of known cardiovascular disease at the time of their breast cancer diagnosis during 1991-2010. Thirty-two percent of them used adjuvant tamoxifen only, 29% used an aromatase inhibitor (AI) only, 20% switched from adjuvant tamoxifen to an AI, and the rest used neither endocrine therapy.

Bruce Jancin/Frontline Medical News

During a mean of 5.5 and maximum 22 years of prospective follow-up, 3,711 women experienced their first cardiovascular disease event. Neither rates of ischemic heart disease nor stroke differed significantly among the groups on tamoxifen, AIs, both in sequence, or neither. However, those on adjuvant AI therapy had an adjusted 26% greater risk of ‘other’ cardiovascular disease, compared with women on tamoxifen only.

The category of ‘other’ cardiovascular disease was comprised of heart failure, arrhythmia, cardiomyopathy, pericarditis, and valvular dysfunction, explained Dr. Haque, a research scientist at Kaiser Permanente of Southern California, Pasadena.

Similarly, women who switched from tamoxifen to an AI were at 28% greater risk of developing ‘other’ cardiovascular disease, compared with those on tamoxifen alone in a multivariate Cox analysis adjusted for age, demographics, comorbid conditions, cancer treatment, tumor characteristics, and use of antihypertensive agents and other cardiovascular medications.

In the subset of 7,982 patients who underwent breast irradiation, those on an adjuvant AI who received left-sided breast radiation therapy were at an adjusted 21% increased risk of all forms of cardiovascular disease – ischemic as well as other – compared with those who got left-sided breast irradiation and took tamoxifen.

As this was an observational study, the results warrant cautious interpretation, Dr. Haque said. Nevertheless, this is a study based upon 72,886 women-years of prospective follow-up and a large number of cardiovascular events, she noted.

The study was funded by the California Breast Cancer Research Program and the National Cancer Institute. Dr. Haque reported having no financial conflicts.

[email protected]

SAN ANTONIO – Though breast cancer survivors have a two- to sixfold higher risk of developing a second primary cancer compared with women in the general population, only a handful of studies have investigated potential ways for women to mitigate this risk, Dr. Christopher I. Li said at the San Antonio Breast Cancer Symposium.

The best established modifiable risk factors for a second primary contralateral breast cancer are obesity, smoking, and excessive alcohol consumption, while chemotherapy, adjuvant aromatase inhibitors, and tamoxifen are protective, he said

In addition, one study has found bisphosphonates have a protective effect against contralateral breast cancer (CBC), and another has identified diabetes mellitus as a significant risk factor. However, these two studies – both conducted by Dr. Li and coworkers – are the only ones to date that have looked at these potential risk modifiers. Confirmatory studies are warranted, emphasized Dr. Li, professor of epidemiology at the University of Washington and head of the translational research program at the Fred Hutchinson Cancer Research Center, Seattle.

An estimated 10% of breast cancer survivors will develop a second, distinct primary cancer. The most common site is the contralateral breast. Indeed, 35% of all second primary cancers in breast cancer survivors occur there. Lung cancer is next most common, accounting for 18%, followed by endometrial cancer at 10%, and colorectal cancer, which comprises 8% of all secondary primary cancers in breast cancer survivors.

Despite the high incidence of CBC, only three studies with 200 or more cases have looked at modifiable risk factors.

One was a population-based nested case-control study by Dr. Li and coworkers. It included 367 CBC cases and a control group of 734 matched breast cancer survivors without a second primary cancer. The investigators identified three modifiable risk factors for CBC: a body mass index of 30 kg/m² or greater, associated with an adjusted 1.5-fold increased risk; consumption of at least seven alcoholic drinks per week after the first breast cancer diagnosis, with a 1.9-fold risk; and current smoking, which conferred a 2.2-fold increased risk.

Upon further analysis, however, an important interaction was noted between alcohol consumption and current smoking such that neither behavior alone was associated with significantly increased risk of CBC. But current smokers who also drank at least seven alcoholic beverages per week were at a highly significant 7.2-fold increased risk (J. Clin. Oncol. 2009;27:5312-8).

Today, bisphosphonates are widely prescribed to prevent and treat bone metastases in breast cancer patients. Dr. Li and coinvestigators conducted a nested case-control study looking at the use of bisphosphonates for another indication: the prevention of osteoporosis-related events. The study comparison involved 351 patients with CBC and 662 controls who were breast cancer survivors without CBC. They found that patients who had ever used a bisphosphonate for 6 months or longer were 47% less likely to develop a CBC.

Moreover, the protective effect increased with duration of therapy. Among current bisphosphonate users who had been taking the medication for at least 6 months, there was an adjusted 59% reduction in the risk of CBC. For current users of at least 12 months, there was a 69% reduction in relative risk compared to nonusers. And among current users of a bisphosphonate for 24 months or longer, the relative risk reduction climbed to 79%, (J. Natl. Cancer Inst. 2011;103:1752-60).

The diabetes study included 332 patients who developed a second primary CBC and 616 matched controls with only a first breast cancer. Women diagnosed with diabetes prior to age 54 had a 6.2-fold increased risk of CBC after Dr. Li and coworkers controlled for obesity and other potential confounders in a conditional logistic regression analysis, while those diagnosed with diabetes at age 55 or older had a twofold increased risk (Breast Cancer Res. Treat. 2011;125:545-51). If these findings are confirmed in another study, more frequent surveillance for CBC will be warranted in diabetic breast cancer survivors, Dr. Li said.

One risk factor for CBC that patients can’t modify involves their breast cancer subtype. In another population-based nested case-control study, this one involving 482 women with a first breast cancer followed by a CBC and 1,506 controls with only a first breast cancer, Dr. Li and colleagues showed that women with HER2-overexpressing primary disease – estrogen receptor-negative/HER2-positive tumors – had a twofold greater likelihood of CBC compared with women who were ER-positive/HER2 positive.

Women with triple-negative breast cancer had an increased risk of CBC that did not become significant until at least 4 years had gone by since diagnosis of the first breast cancer. At that point they had a 2.2-fold greater risk of CBC and patients with HER2-overexpressing disease had a 2.7-fold greater risk compared with ER-positive/HER2-positive patients.

Patients with these more aggressive breast cancer subtypes – the HER2-overexpressing and triple-negative forms of the disease – were also at particularly high risk for more advanced stage CBC. Their CBCs were greater than three times more likely to be at a regional or distant stage at diagnosis than those occurring in patients with ER-positive/HER2-positive primary breast cancer (Breast Cancer Res. Treat. 2012;135:849-55).

Dr. Li closed by noting that the growing problem of CBC is finally receiving extra attention from funding agencies. A new Consortium of CBC has been created, enabling investigators from 28 different CBC studies to interact more closely. The consortium is led by physicians at Memorial Sloan Kettering Cancer Center in New York, and at Fred Hutchinson.

The National Cancer Institute recently approved funding for a new population-based case-control study focusing on second primary cancers. It will include 700 controls with only a single breast cancer diagnosis along with 600 women with a second primary cancer of the lung, 600 with CBC, 350 with a second primary colorectal cancer, and another 350 with a second primary in the endometrium. The study will look in-depth at risk factors, treatments, and clinical and molecular characteristics and their impact on second primary cancers in breast cancer patients.

“We really hope through this study to move the field forward,” Dr. Li said.

His studies have been funded by the National Institutes of Health. He reported having no financial conflicts.

[email protected]

SAN ANTONIO – Though breast cancer survivors have a two- to sixfold higher risk of developing a second primary cancer compared with women in the general population, only a handful of studies have investigated potential ways for women to mitigate this risk, Dr. Christopher I. Li said at the San Antonio Breast Cancer Symposium.

The best established modifiable risk factors for a second primary contralateral breast cancer are obesity, smoking, and excessive alcohol consumption, while chemotherapy, adjuvant aromatase inhibitors, and tamoxifen are protective, he said

In addition, one study has found bisphosphonates have a protective effect against contralateral breast cancer (CBC), and another has identified diabetes mellitus as a significant risk factor. However, these two studies – both conducted by Dr. Li and coworkers – are the only ones to date that have looked at these potential risk modifiers. Confirmatory studies are warranted, emphasized Dr. Li, professor of epidemiology at the University of Washington and head of the translational research program at the Fred Hutchinson Cancer Research Center, Seattle.

An estimated 10% of breast cancer survivors will develop a second, distinct primary cancer. The most common site is the contralateral breast. Indeed, 35% of all second primary cancers in breast cancer survivors occur there. Lung cancer is next most common, accounting for 18%, followed by endometrial cancer at 10%, and colorectal cancer, which comprises 8% of all secondary primary cancers in breast cancer survivors.

Despite the high incidence of CBC, only three studies with 200 or more cases have looked at modifiable risk factors.

One was a population-based nested case-control study by Dr. Li and coworkers. It included 367 CBC cases and a control group of 734 matched breast cancer survivors without a second primary cancer. The investigators identified three modifiable risk factors for CBC: a body mass index of 30 kg/m² or greater, associated with an adjusted 1.5-fold increased risk; consumption of at least seven alcoholic drinks per week after the first breast cancer diagnosis, with a 1.9-fold risk; and current smoking, which conferred a 2.2-fold increased risk.

Upon further analysis, however, an important interaction was noted between alcohol consumption and current smoking such that neither behavior alone was associated with significantly increased risk of CBC. But current smokers who also drank at least seven alcoholic beverages per week were at a highly significant 7.2-fold increased risk (J. Clin. Oncol. 2009;27:5312-8).

Today, bisphosphonates are widely prescribed to prevent and treat bone metastases in breast cancer patients. Dr. Li and coinvestigators conducted a nested case-control study looking at the use of bisphosphonates for another indication: the prevention of osteoporosis-related events. The study comparison involved 351 patients with CBC and 662 controls who were breast cancer survivors without CBC. They found that patients who had ever used a bisphosphonate for 6 months or longer were 47% less likely to develop a CBC.

Moreover, the protective effect increased with duration of therapy. Among current bisphosphonate users who had been taking the medication for at least 6 months, there was an adjusted 59% reduction in the risk of CBC. For current users of at least 12 months, there was a 69% reduction in relative risk compared to nonusers. And among current users of a bisphosphonate for 24 months or longer, the relative risk reduction climbed to 79%, (J. Natl. Cancer Inst. 2011;103:1752-60).

The diabetes study included 332 patients who developed a second primary CBC and 616 matched controls with only a first breast cancer. Women diagnosed with diabetes prior to age 54 had a 6.2-fold increased risk of CBC after Dr. Li and coworkers controlled for obesity and other potential confounders in a conditional logistic regression analysis, while those diagnosed with diabetes at age 55 or older had a twofold increased risk (Breast Cancer Res. Treat. 2011;125:545-51). If these findings are confirmed in another study, more frequent surveillance for CBC will be warranted in diabetic breast cancer survivors, Dr. Li said.

One risk factor for CBC that patients can’t modify involves their breast cancer subtype. In another population-based nested case-control study, this one involving 482 women with a first breast cancer followed by a CBC and 1,506 controls with only a first breast cancer, Dr. Li and colleagues showed that women with HER2-overexpressing primary disease – estrogen receptor-negative/HER2-positive tumors – had a twofold greater likelihood of CBC compared with women who were ER-positive/HER2 positive.

Women with triple-negative breast cancer had an increased risk of CBC that did not become significant until at least 4 years had gone by since diagnosis of the first breast cancer. At that point they had a 2.2-fold greater risk of CBC and patients with HER2-overexpressing disease had a 2.7-fold greater risk compared with ER-positive/HER2-positive patients.

Patients with these more aggressive breast cancer subtypes – the HER2-overexpressing and triple-negative forms of the disease – were also at particularly high risk for more advanced stage CBC. Their CBCs were greater than three times more likely to be at a regional or distant stage at diagnosis than those occurring in patients with ER-positive/HER2-positive primary breast cancer (Breast Cancer Res. Treat. 2012;135:849-55).

Dr. Li closed by noting that the growing problem of CBC is finally receiving extra attention from funding agencies. A new Consortium of CBC has been created, enabling investigators from 28 different CBC studies to interact more closely. The consortium is led by physicians at Memorial Sloan Kettering Cancer Center in New York, and at Fred Hutchinson.

The National Cancer Institute recently approved funding for a new population-based case-control study focusing on second primary cancers. It will include 700 controls with only a single breast cancer diagnosis along with 600 women with a second primary cancer of the lung, 600 with CBC, 350 with a second primary colorectal cancer, and another 350 with a second primary in the endometrium. The study will look in-depth at risk factors, treatments, and clinical and molecular characteristics and their impact on second primary cancers in breast cancer patients.

“We really hope through this study to move the field forward,” Dr. Li said.

His studies have been funded by the National Institutes of Health. He reported having no financial conflicts.

[email protected]

SAN ANTONIO – Though breast cancer survivors have a two- to sixfold higher risk of developing a second primary cancer compared with women in the general population, only a handful of studies have investigated potential ways for women to mitigate this risk, Dr. Christopher I. Li said at the San Antonio Breast Cancer Symposium.

The best established modifiable risk factors for a second primary contralateral breast cancer are obesity, smoking, and excessive alcohol consumption, while chemotherapy, adjuvant aromatase inhibitors, and tamoxifen are protective, he said

In addition, one study has found bisphosphonates have a protective effect against contralateral breast cancer (CBC), and another has identified diabetes mellitus as a significant risk factor. However, these two studies – both conducted by Dr. Li and coworkers – are the only ones to date that have looked at these potential risk modifiers. Confirmatory studies are warranted, emphasized Dr. Li, professor of epidemiology at the University of Washington and head of the translational research program at the Fred Hutchinson Cancer Research Center, Seattle.

An estimated 10% of breast cancer survivors will develop a second, distinct primary cancer. The most common site is the contralateral breast. Indeed, 35% of all second primary cancers in breast cancer survivors occur there. Lung cancer is next most common, accounting for 18%, followed by endometrial cancer at 10%, and colorectal cancer, which comprises 8% of all secondary primary cancers in breast cancer survivors.

Despite the high incidence of CBC, only three studies with 200 or more cases have looked at modifiable risk factors.

One was a population-based nested case-control study by Dr. Li and coworkers. It included 367 CBC cases and a control group of 734 matched breast cancer survivors without a second primary cancer. The investigators identified three modifiable risk factors for CBC: a body mass index of 30 kg/m² or greater, associated with an adjusted 1.5-fold increased risk; consumption of at least seven alcoholic drinks per week after the first breast cancer diagnosis, with a 1.9-fold risk; and current smoking, which conferred a 2.2-fold increased risk.

Upon further analysis, however, an important interaction was noted between alcohol consumption and current smoking such that neither behavior alone was associated with significantly increased risk of CBC. But current smokers who also drank at least seven alcoholic beverages per week were at a highly significant 7.2-fold increased risk (J. Clin. Oncol. 2009;27:5312-8).

Today, bisphosphonates are widely prescribed to prevent and treat bone metastases in breast cancer patients. Dr. Li and coinvestigators conducted a nested case-control study looking at the use of bisphosphonates for another indication: the prevention of osteoporosis-related events. The study comparison involved 351 patients with CBC and 662 controls who were breast cancer survivors without CBC. They found that patients who had ever used a bisphosphonate for 6 months or longer were 47% less likely to develop a CBC.

Moreover, the protective effect increased with duration of therapy. Among current bisphosphonate users who had been taking the medication for at least 6 months, there was an adjusted 59% reduction in the risk of CBC. For current users of at least 12 months, there was a 69% reduction in relative risk compared to nonusers. And among current users of a bisphosphonate for 24 months or longer, the relative risk reduction climbed to 79%, (J. Natl. Cancer Inst. 2011;103:1752-60).

The diabetes study included 332 patients who developed a second primary CBC and 616 matched controls with only a first breast cancer. Women diagnosed with diabetes prior to age 54 had a 6.2-fold increased risk of CBC after Dr. Li and coworkers controlled for obesity and other potential confounders in a conditional logistic regression analysis, while those diagnosed with diabetes at age 55 or older had a twofold increased risk (Breast Cancer Res. Treat. 2011;125:545-51). If these findings are confirmed in another study, more frequent surveillance for CBC will be warranted in diabetic breast cancer survivors, Dr. Li said.

One risk factor for CBC that patients can’t modify involves their breast cancer subtype. In another population-based nested case-control study, this one involving 482 women with a first breast cancer followed by a CBC and 1,506 controls with only a first breast cancer, Dr. Li and colleagues showed that women with HER2-overexpressing primary disease – estrogen receptor-negative/HER2-positive tumors – had a twofold greater likelihood of CBC compared with women who were ER-positive/HER2 positive.

Women with triple-negative breast cancer had an increased risk of CBC that did not become significant until at least 4 years had gone by since diagnosis of the first breast cancer. At that point they had a 2.2-fold greater risk of CBC and patients with HER2-overexpressing disease had a 2.7-fold greater risk compared with ER-positive/HER2-positive patients.

Patients with these more aggressive breast cancer subtypes – the HER2-overexpressing and triple-negative forms of the disease – were also at particularly high risk for more advanced stage CBC. Their CBCs were greater than three times more likely to be at a regional or distant stage at diagnosis than those occurring in patients with ER-positive/HER2-positive primary breast cancer (Breast Cancer Res. Treat. 2012;135:849-55).

Dr. Li closed by noting that the growing problem of CBC is finally receiving extra attention from funding agencies. A new Consortium of CBC has been created, enabling investigators from 28 different CBC studies to interact more closely. The consortium is led by physicians at Memorial Sloan Kettering Cancer Center in New York, and at Fred Hutchinson.

The National Cancer Institute recently approved funding for a new population-based case-control study focusing on second primary cancers. It will include 700 controls with only a single breast cancer diagnosis along with 600 women with a second primary cancer of the lung, 600 with CBC, 350 with a second primary colorectal cancer, and another 350 with a second primary in the endometrium. The study will look in-depth at risk factors, treatments, and clinical and molecular characteristics and their impact on second primary cancers in breast cancer patients.

“We really hope through this study to move the field forward,” Dr. Li said.

His studies have been funded by the National Institutes of Health. He reported having no financial conflicts.

[email protected]

SAN ANTONIO – Hefty reductions in annual health care spending for breast cancer therapy would be achieved if physicians increased their use of evidence-based adjuvant radiation therapy following lumpectomy for early-stage breast cancer, according to Dr. Rachel A. Greenup.

The potential savings would amount to $164 million annually, based on the American College of Surgeons National Cancer Data Base for the year 2011. And since that database captures only about 70% of all newly diagnosed cancers in the United States, that savings figure is likely an underestimate, according to Dr. Greenup, a surgical oncologist at Duke University, Durham, N.C.

She and her coinvestigators identified 43,247 women in the national database with clinically node-negative, T1-T2 invasive breast cancer treated by lumpectomy during 2011. Their median age was 63 years, with a median tumor size of 1.2 cm. Only 26% of women received the least expensive adjuvant radiation therapy for which they were potentially eligible based upon current guidelines and best practices. Sixty-seven percent of patients received more costly regimens.

Overall, 22% of the women were deemed by investigators to be eligible for no radiotherapy because they fit the criteria laid out in the CALGB (Cancer and Leukemia Group B) 9493 study: age 70 years or older, with T1N0, estrogen receptor–positive disease. CALGB 9493 demonstrated at median follow-ups of 5 years (N. Engl. J. Med. 2004;351:971-7) and 12.6 years (J. Clin. Oncol. 2013;31:2382-7) that women who fit that profile could safely forego radiotherapy.

The investigators considered another 62% of patients to be eligible for hypofractionated whole breast irradiation (HF-WBI), defined as 15-24 fractions at 40-58 Gy, as their least costly appropriate radiotherapy option because they were at least 50 years old with T1-T2 NO invasive breast cancer. Sixteen percent of patients were deemed eligible for conventional fractionated whole breast irradiation (CF-WBI) as their least expensive option.

Treatment costs were determined using the Medicare Physician Fee Schedule payment data for 2011 and the average procedural codes billed per regimen. The cost per patient was $13,358.37 for CF-WBI and $8,327.98 for HF-WBI.

Of the 9,651 women considered eligible for no radiation therapy, only 36% actually did not undergo irradiation. Forty-four percent had CF-WBI, 18% had HF-WBI, and the rest had accelerated partial breast irradiation. The total cost of radiation therapy in this subgroup was $72.2 million.

Among the considerably larger group for whom HF-WBI was deemed the least costly radiation therapy option for which they were eligible, 68% had CF-WBI, 17% had no radiotherapy, and only 6.5% received HF-WBI. The total cost of radiation therapy in this group was $276.8 million in 2011. Had they undergone evidence-based therapy, the cost would have dropped to $185 million, Dr. Greenup said at the San Antonio Breast Cancer Symposium.

For the 6,685 women who were considered candidates for CF-WBI, 75% received that form of radiation therapy, 7% got HF-WBI, and 18% received no radiotherapy. Their total radiation therapy costs amounted to $71.2 million.

The total estimated cost of actual radiation treatment in the study population was $420.2 million, compared with $256.2 million, or 39% less, had the women received the least expensive regimen for which they were eligible.

An estimated $125 billion is spent annually on cancer treatment in the United States, with breast cancer therapy accounting for the largest proportion of that, Dr. Greenup noted.

She reported having no relevant financial conflicts.

[email protected]

SAN ANTONIO – Hefty reductions in annual health care spending for breast cancer therapy would be achieved if physicians increased their use of evidence-based adjuvant radiation therapy following lumpectomy for early-stage breast cancer, according to Dr. Rachel A. Greenup.

The potential savings would amount to $164 million annually, based on the American College of Surgeons National Cancer Data Base for the year 2011. And since that database captures only about 70% of all newly diagnosed cancers in the United States, that savings figure is likely an underestimate, according to Dr. Greenup, a surgical oncologist at Duke University, Durham, N.C.

She and her coinvestigators identified 43,247 women in the national database with clinically node-negative, T1-T2 invasive breast cancer treated by lumpectomy during 2011. Their median age was 63 years, with a median tumor size of 1.2 cm. Only 26% of women received the least expensive adjuvant radiation therapy for which they were potentially eligible based upon current guidelines and best practices. Sixty-seven percent of patients received more costly regimens.

Overall, 22% of the women were deemed by investigators to be eligible for no radiotherapy because they fit the criteria laid out in the CALGB (Cancer and Leukemia Group B) 9493 study: age 70 years or older, with T1N0, estrogen receptor–positive disease. CALGB 9493 demonstrated at median follow-ups of 5 years (N. Engl. J. Med. 2004;351:971-7) and 12.6 years (J. Clin. Oncol. 2013;31:2382-7) that women who fit that profile could safely forego radiotherapy.

The investigators considered another 62% of patients to be eligible for hypofractionated whole breast irradiation (HF-WBI), defined as 15-24 fractions at 40-58 Gy, as their least costly appropriate radiotherapy option because they were at least 50 years old with T1-T2 NO invasive breast cancer. Sixteen percent of patients were deemed eligible for conventional fractionated whole breast irradiation (CF-WBI) as their least expensive option.

Treatment costs were determined using the Medicare Physician Fee Schedule payment data for 2011 and the average procedural codes billed per regimen. The cost per patient was $13,358.37 for CF-WBI and $8,327.98 for HF-WBI.

Of the 9,651 women considered eligible for no radiation therapy, only 36% actually did not undergo irradiation. Forty-four percent had CF-WBI, 18% had HF-WBI, and the rest had accelerated partial breast irradiation. The total cost of radiation therapy in this subgroup was $72.2 million.

Among the considerably larger group for whom HF-WBI was deemed the least costly radiation therapy option for which they were eligible, 68% had CF-WBI, 17% had no radiotherapy, and only 6.5% received HF-WBI. The total cost of radiation therapy in this group was $276.8 million in 2011. Had they undergone evidence-based therapy, the cost would have dropped to $185 million, Dr. Greenup said at the San Antonio Breast Cancer Symposium.

For the 6,685 women who were considered candidates for CF-WBI, 75% received that form of radiation therapy, 7% got HF-WBI, and 18% received no radiotherapy. Their total radiation therapy costs amounted to $71.2 million.

The total estimated cost of actual radiation treatment in the study population was $420.2 million, compared with $256.2 million, or 39% less, had the women received the least expensive regimen for which they were eligible.

An estimated $125 billion is spent annually on cancer treatment in the United States, with breast cancer therapy accounting for the largest proportion of that, Dr. Greenup noted.

She reported having no relevant financial conflicts.

[email protected]

SAN ANTONIO – Hefty reductions in annual health care spending for breast cancer therapy would be achieved if physicians increased their use of evidence-based adjuvant radiation therapy following lumpectomy for early-stage breast cancer, according to Dr. Rachel A. Greenup.

The potential savings would amount to $164 million annually, based on the American College of Surgeons National Cancer Data Base for the year 2011. And since that database captures only about 70% of all newly diagnosed cancers in the United States, that savings figure is likely an underestimate, according to Dr. Greenup, a surgical oncologist at Duke University, Durham, N.C.

She and her coinvestigators identified 43,247 women in the national database with clinically node-negative, T1-T2 invasive breast cancer treated by lumpectomy during 2011. Their median age was 63 years, with a median tumor size of 1.2 cm. Only 26% of women received the least expensive adjuvant radiation therapy for which they were potentially eligible based upon current guidelines and best practices. Sixty-seven percent of patients received more costly regimens.

Overall, 22% of the women were deemed by investigators to be eligible for no radiotherapy because they fit the criteria laid out in the CALGB (Cancer and Leukemia Group B) 9493 study: age 70 years or older, with T1N0, estrogen receptor–positive disease. CALGB 9493 demonstrated at median follow-ups of 5 years (N. Engl. J. Med. 2004;351:971-7) and 12.6 years (J. Clin. Oncol. 2013;31:2382-7) that women who fit that profile could safely forego radiotherapy.

The investigators considered another 62% of patients to be eligible for hypofractionated whole breast irradiation (HF-WBI), defined as 15-24 fractions at 40-58 Gy, as their least costly appropriate radiotherapy option because they were at least 50 years old with T1-T2 NO invasive breast cancer. Sixteen percent of patients were deemed eligible for conventional fractionated whole breast irradiation (CF-WBI) as their least expensive option.

Treatment costs were determined using the Medicare Physician Fee Schedule payment data for 2011 and the average procedural codes billed per regimen. The cost per patient was $13,358.37 for CF-WBI and $8,327.98 for HF-WBI.

Of the 9,651 women considered eligible for no radiation therapy, only 36% actually did not undergo irradiation. Forty-four percent had CF-WBI, 18% had HF-WBI, and the rest had accelerated partial breast irradiation. The total cost of radiation therapy in this subgroup was $72.2 million.

Among the considerably larger group for whom HF-WBI was deemed the least costly radiation therapy option for which they were eligible, 68% had CF-WBI, 17% had no radiotherapy, and only 6.5% received HF-WBI. The total cost of radiation therapy in this group was $276.8 million in 2011. Had they undergone evidence-based therapy, the cost would have dropped to $185 million, Dr. Greenup said at the San Antonio Breast Cancer Symposium.

For the 6,685 women who were considered candidates for CF-WBI, 75% received that form of radiation therapy, 7% got HF-WBI, and 18% received no radiotherapy. Their total radiation therapy costs amounted to $71.2 million.

The total estimated cost of actual radiation treatment in the study population was $420.2 million, compared with $256.2 million, or 39% less, had the women received the least expensive regimen for which they were eligible.

An estimated $125 billion is spent annually on cancer treatment in the United States, with breast cancer therapy accounting for the largest proportion of that, Dr. Greenup noted.

She reported having no relevant financial conflicts.

[email protected]

SAN ANTONIO – Extended follow-up of the nearly 5,000 women enrolled in the phase III multicenter E1199 trial has provided a wealth of new findings – and additional leads – regarding optimal adjuvant chemotherapy in patients with axillary lymph node–positive or high-risk, lymph node–negative breast cancer.

“The relative effectiveness of weekly paclitaxel and every-3-week docetaxel may vary by subtype,” Dr. Joseph A. Sparano reported at the San Antonio Breast Cancer Symposium.

The E1199 trial, conducted in 1999-2001, included 4,950 breast cancer patients who first received four cycles of standard adjuvant chemotherapy consisting of intravenous doxorubicin and cyclophosphamide at 3-week intervals. They were then assigned in a 2x2 factorial design to intravenous paclitaxel (Abraxane) at the then-standard 3-week intervals for four cycles, to weekly paclitaxel for 12 weeks, or to docetaxel (Taxotere) given at either of the same two dosing schedules.

Bruce Jancin/Frontline Medical News

The goal was to determine the optimally effective adjuvant taxane and dosing regimen. And in the initial report based upon a median 5.3 years of follow-up (N. Engl. J. Med. 2008;358:1663-71), weekly paclitaxel was the clear winner. It was associated with a 27% improvement in the likelihood of disease-free survival (DFS) and a 32% gain in overall survival (OS), compared with paclitaxel given every 3 weeks. Docetaxel every 3 weeks also resulted in improved DFS, but not in OS.

Dr. Sparano’s newly updated analysis was based upon a median 12.1 years of follow-up. By this point the number of DFS events – defined as recurrence, contralateral breast cancer, or death – had climbed to 1,639, compared with 1,058 in the initial report. The all-cause death count had risen from 686 to 1,283.

With the extended follow-up, both weekly paclitaxel and docetaxel every 3 weeks still remained superior to every-3-weeks paclitaxel in terms of DFS, with relative risk reductions of 16% and 21% for DFS events, respectively. However, trends favoring these two regimens in terms of OS didn’t reach statistical significance, reported Dr. Sparano, professor of medicine and women’s health at Albert Einstein College of Medicine, New York.

Among the more interesting findings to emerge from the extended analysis was the differential treatment response based upon breast cancer subtype. Among the 1,025 women with triple-negative breast cancer (TNBC), weekly paclitaxel was associated with highly significant relative risk reductions of 31% both for DFS events and mortality. This regimen boosted the 10-year DFS rate from 59% with every-3-weeks paclitaxel to 69%, while improving 10-year overall survival from 66% to 75%.

“Our findings also show that there remains substantial room for improvement in this population, despite the improvement seen with weekly paclitaxel,” the medical oncologist observed.

This is the rationale for the pending NRG-BR003 trial, in which patients with TNBC are randomized to four cycles of adjuvant chemotherapy followed by weekly paclitaxel for 12 weeks, as in the most effective arm of E1199, or to the same regimen supplemented by carboplatin in an effort to enhance outcomes.

In E1199, TNBC was associated with a very high annual risk of cancer recurrence within the first 3 years, which declined substantially thereafter. In contrast, for the 2,785 participants with hormone receptor (HR)-positive/HER2-negative breast cancer, the recurrence risk remained persistently strong beyond 5 years.

Obesity, which was present in 35% of all E1199 participants, was associated with worse outcomes in the HR-positive/HER2-negative group, where in a multivariate analysis it was independently associated with a 23% reduction in OS and a recurrence risk peaking 3-8 years after diagnosis.

“I think an important finding from this study is that obesity tends to be associated with later relapse. So if dietary and lifestyle and other metabolic-type interventions are going to be successful, there may be an adequate window to implement those changes and have a real impact on outcomes,” according to Dr. Sparano.

Black race was also independently associated with worse outcomes in HR-positive/HER2-negative patients but not in those with TNBC. In nonobese women with HER-positive/HER2-negative disease, black race was associated with roughly 2.3-fold increased risks of DFS events and mortality.

“These findings indicate an effect of race independent of obesity. That’s an important finding given the fact that obesity rates were twofold higher in patients of black race,” Dr. Sparano said.

In women with HR-positive/HER2-negative breast cancer, the only study regimen that proved more effective than paclitaxel every 3 weeks was docetaxel every 3 weeks, which in the extended follow-up resulted in a 24% reduction in the risk of DFS events but no significant advantage in OS.

“This suggests that attention to extended adjuvant endocrine therapy may be more relevant in this subpopulation, which is at risk for late relapse, particularly at the time of this study, when extended adjuvant therapy was not common practice,” he noted.

Late relapse remains “a vexing problem” in HR-positive/HER2-negative patients, Dr. Sparano continued. A major effort is underway to address this via an ECOG-ACRIN North American Breast Cancer Intergroup project designed to establish a late-relapse biospecimen bank featuring blood and/or tumor samples from 10,000 women enrolled in the TAILORx (Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer) and E5103 trials.

[email protected]

SAN ANTONIO – Extended follow-up of the nearly 5,000 women enrolled in the phase III multicenter E1199 trial has provided a wealth of new findings – and additional leads – regarding optimal adjuvant chemotherapy in patients with axillary lymph node–positive or high-risk, lymph node–negative breast cancer.

“The relative effectiveness of weekly paclitaxel and every-3-week docetaxel may vary by subtype,” Dr. Joseph A. Sparano reported at the San Antonio Breast Cancer Symposium.

The E1199 trial, conducted in 1999-2001, included 4,950 breast cancer patients who first received four cycles of standard adjuvant chemotherapy consisting of intravenous doxorubicin and cyclophosphamide at 3-week intervals. They were then assigned in a 2x2 factorial design to intravenous paclitaxel (Abraxane) at the then-standard 3-week intervals for four cycles, to weekly paclitaxel for 12 weeks, or to docetaxel (Taxotere) given at either of the same two dosing schedules.

Bruce Jancin/Frontline Medical News

The goal was to determine the optimally effective adjuvant taxane and dosing regimen. And in the initial report based upon a median 5.3 years of follow-up (N. Engl. J. Med. 2008;358:1663-71), weekly paclitaxel was the clear winner. It was associated with a 27% improvement in the likelihood of disease-free survival (DFS) and a 32% gain in overall survival (OS), compared with paclitaxel given every 3 weeks. Docetaxel every 3 weeks also resulted in improved DFS, but not in OS.

Dr. Sparano’s newly updated analysis was based upon a median 12.1 years of follow-up. By this point the number of DFS events – defined as recurrence, contralateral breast cancer, or death – had climbed to 1,639, compared with 1,058 in the initial report. The all-cause death count had risen from 686 to 1,283.

With the extended follow-up, both weekly paclitaxel and docetaxel every 3 weeks still remained superior to every-3-weeks paclitaxel in terms of DFS, with relative risk reductions of 16% and 21% for DFS events, respectively. However, trends favoring these two regimens in terms of OS didn’t reach statistical significance, reported Dr. Sparano, professor of medicine and women’s health at Albert Einstein College of Medicine, New York.

Among the more interesting findings to emerge from the extended analysis was the differential treatment response based upon breast cancer subtype. Among the 1,025 women with triple-negative breast cancer (TNBC), weekly paclitaxel was associated with highly significant relative risk reductions of 31% both for DFS events and mortality. This regimen boosted the 10-year DFS rate from 59% with every-3-weeks paclitaxel to 69%, while improving 10-year overall survival from 66% to 75%.

“Our findings also show that there remains substantial room for improvement in this population, despite the improvement seen with weekly paclitaxel,” the medical oncologist observed.

This is the rationale for the pending NRG-BR003 trial, in which patients with TNBC are randomized to four cycles of adjuvant chemotherapy followed by weekly paclitaxel for 12 weeks, as in the most effective arm of E1199, or to the same regimen supplemented by carboplatin in an effort to enhance outcomes.

In E1199, TNBC was associated with a very high annual risk of cancer recurrence within the first 3 years, which declined substantially thereafter. In contrast, for the 2,785 participants with hormone receptor (HR)-positive/HER2-negative breast cancer, the recurrence risk remained persistently strong beyond 5 years.

Obesity, which was present in 35% of all E1199 participants, was associated with worse outcomes in the HR-positive/HER2-negative group, where in a multivariate analysis it was independently associated with a 23% reduction in OS and a recurrence risk peaking 3-8 years after diagnosis.

“I think an important finding from this study is that obesity tends to be associated with later relapse. So if dietary and lifestyle and other metabolic-type interventions are going to be successful, there may be an adequate window to implement those changes and have a real impact on outcomes,” according to Dr. Sparano.

Black race was also independently associated with worse outcomes in HR-positive/HER2-negative patients but not in those with TNBC. In nonobese women with HER-positive/HER2-negative disease, black race was associated with roughly 2.3-fold increased risks of DFS events and mortality.

“These findings indicate an effect of race independent of obesity. That’s an important finding given the fact that obesity rates were twofold higher in patients of black race,” Dr. Sparano said.

In women with HR-positive/HER2-negative breast cancer, the only study regimen that proved more effective than paclitaxel every 3 weeks was docetaxel every 3 weeks, which in the extended follow-up resulted in a 24% reduction in the risk of DFS events but no significant advantage in OS.

“This suggests that attention to extended adjuvant endocrine therapy may be more relevant in this subpopulation, which is at risk for late relapse, particularly at the time of this study, when extended adjuvant therapy was not common practice,” he noted.

Late relapse remains “a vexing problem” in HR-positive/HER2-negative patients, Dr. Sparano continued. A major effort is underway to address this via an ECOG-ACRIN North American Breast Cancer Intergroup project designed to establish a late-relapse biospecimen bank featuring blood and/or tumor samples from 10,000 women enrolled in the TAILORx (Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer) and E5103 trials.

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SAN ANTONIO – Extended follow-up of the nearly 5,000 women enrolled in the phase III multicenter E1199 trial has provided a wealth of new findings – and additional leads – regarding optimal adjuvant chemotherapy in patients with axillary lymph node–positive or high-risk, lymph node–negative breast cancer.

“The relative effectiveness of weekly paclitaxel and every-3-week docetaxel may vary by subtype,” Dr. Joseph A. Sparano reported at the San Antonio Breast Cancer Symposium.

The E1199 trial, conducted in 1999-2001, included 4,950 breast cancer patients who first received four cycles of standard adjuvant chemotherapy consisting of intravenous doxorubicin and cyclophosphamide at 3-week intervals. They were then assigned in a 2x2 factorial design to intravenous paclitaxel (Abraxane) at the then-standard 3-week intervals for four cycles, to weekly paclitaxel for 12 weeks, or to docetaxel (Taxotere) given at either of the same two dosing schedules.

Bruce Jancin/Frontline Medical News

The goal was to determine the optimally effective adjuvant taxane and dosing regimen. And in the initial report based upon a median 5.3 years of follow-up (N. Engl. J. Med. 2008;358:1663-71), weekly paclitaxel was the clear winner. It was associated with a 27% improvement in the likelihood of disease-free survival (DFS) and a 32% gain in overall survival (OS), compared with paclitaxel given every 3 weeks. Docetaxel every 3 weeks also resulted in improved DFS, but not in OS.

Dr. Sparano’s newly updated analysis was based upon a median 12.1 years of follow-up. By this point the number of DFS events – defined as recurrence, contralateral breast cancer, or death – had climbed to 1,639, compared with 1,058 in the initial report. The all-cause death count had risen from 686 to 1,283.

With the extended follow-up, both weekly paclitaxel and docetaxel every 3 weeks still remained superior to every-3-weeks paclitaxel in terms of DFS, with relative risk reductions of 16% and 21% for DFS events, respectively. However, trends favoring these two regimens in terms of OS didn’t reach statistical significance, reported Dr. Sparano, professor of medicine and women’s health at Albert Einstein College of Medicine, New York.

Among the more interesting findings to emerge from the extended analysis was the differential treatment response based upon breast cancer subtype. Among the 1,025 women with triple-negative breast cancer (TNBC), weekly paclitaxel was associated with highly significant relative risk reductions of 31% both for DFS events and mortality. This regimen boosted the 10-year DFS rate from 59% with every-3-weeks paclitaxel to 69%, while improving 10-year overall survival from 66% to 75%.

“Our findings also show that there remains substantial room for improvement in this population, despite the improvement seen with weekly paclitaxel,” the medical oncologist observed.

This is the rationale for the pending NRG-BR003 trial, in which patients with TNBC are randomized to four cycles of adjuvant chemotherapy followed by weekly paclitaxel for 12 weeks, as in the most effective arm of E1199, or to the same regimen supplemented by carboplatin in an effort to enhance outcomes.

In E1199, TNBC was associated with a very high annual risk of cancer recurrence within the first 3 years, which declined substantially thereafter. In contrast, for the 2,785 participants with hormone receptor (HR)-positive/HER2-negative breast cancer, the recurrence risk remained persistently strong beyond 5 years.

Obesity, which was present in 35% of all E1199 participants, was associated with worse outcomes in the HR-positive/HER2-negative group, where in a multivariate analysis it was independently associated with a 23% reduction in OS and a recurrence risk peaking 3-8 years after diagnosis.

“I think an important finding from this study is that obesity tends to be associated with later relapse. So if dietary and lifestyle and other metabolic-type interventions are going to be successful, there may be an adequate window to implement those changes and have a real impact on outcomes,” according to Dr. Sparano.

Black race was also independently associated with worse outcomes in HR-positive/HER2-negative patients but not in those with TNBC. In nonobese women with HER-positive/HER2-negative disease, black race was associated with roughly 2.3-fold increased risks of DFS events and mortality.

“These findings indicate an effect of race independent of obesity. That’s an important finding given the fact that obesity rates were twofold higher in patients of black race,” Dr. Sparano said.

In women with HR-positive/HER2-negative breast cancer, the only study regimen that proved more effective than paclitaxel every 3 weeks was docetaxel every 3 weeks, which in the extended follow-up resulted in a 24% reduction in the risk of DFS events but no significant advantage in OS.

“This suggests that attention to extended adjuvant endocrine therapy may be more relevant in this subpopulation, which is at risk for late relapse, particularly at the time of this study, when extended adjuvant therapy was not common practice,” he noted.

Late relapse remains “a vexing problem” in HR-positive/HER2-negative patients, Dr. Sparano continued. A major effort is underway to address this via an ECOG-ACRIN North American Breast Cancer Intergroup project designed to establish a late-relapse biospecimen bank featuring blood and/or tumor samples from 10,000 women enrolled in the TAILORx (Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer) and E5103 trials.

[email protected]