Breast Cancer

SAN ANTONIO – An accelerated course of partial breast irradiation was as effective as whole breast irradiation for women with early breast cancer, with significantly fewer adverse events.

The technique may be a suitable alternative for select patients who wish to minimize side effects without compromising clinical outcomes, Dr. Lorenzo Livi said at the San Antonio Breast Cancer Symposium.

He reported the 5-year results of an Italian study that randomized women with early breast cancer to one of two radiation regimens: conventional (tangential field) fractionated whole breast treatment or accelerated partial breast irradiation plus intensity-modulated radiotherapy.

Michele G. Sullivan/Frontline Medical News

The patients were highly selected, with a primary tumor size of less than 25 mm and negative surgical margins of more than 5 mm, said Dr. Livi, a radiation oncologist at the University of Florence, Italy.

The cohort comprised 520 women. Most (about 85%) were node-negative; 95% of the tumors were estrogen receptor–positive, and 90% were progesterone receptor–positive. The most frequent molecular subtype was luminal A (about 75%); less than 5% were triple-negative.

The median follow-up for this portion of the study was 5 years. There were six ipsilateral breast tumor recurrences – three in each group. There were three local relapses, all in the whole breast irradiation group. The 5-year recurrence rate was 1.4% in the whole breast irradiation group and 1.5% in the partial breast irradiation group. The mean time to ipsilateral breast recurrence was 3 years, and there was no significant between-group difference in this timing.

There were 10 contralateral recurrences (seven in the whole breast group vs. three in the partial irradiation group). Distant metastases occurred in seven patients (four and three, respectively).

The 5-year overall survival rate was excellent, Dr. Livi noted: 97% in the whole breast irradiation group and 99% in the partial irradiation group.

Skin toxicity of any grade was significantly less common in the partial group (49 vs. 181). Significantly more patients in the partial irradiation group were completely free of adverse events (197 vs. 93). There were no grade 3 adverse events in either group. Two women in the whole breast irradiation group experienced a grade 2 toxicity- both of these were skin fibrosis.

Almost all patients (90%) reported good or excellent cosmetic results.

Dr. Livi fielded a few questions during the discussion period, one of which dealt with the cost of partial irradiation treatment. Since the procedure is more expensive, and the results similar, the discussant wondered whether it would be worth the additional cost. Dr Livi said the question is difficult for him to answer, because Italy’s national health care system does not charge patients for the treatment. He did say reimbursement for the treatments differs, but he did not elaborate.

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN ANTONIO – An accelerated course of partial breast irradiation was as effective as whole breast irradiation for women with early breast cancer, with significantly fewer adverse events.

The technique may be a suitable alternative for select patients who wish to minimize side effects without compromising clinical outcomes, Dr. Lorenzo Livi said at the San Antonio Breast Cancer Symposium.

He reported the 5-year results of an Italian study that randomized women with early breast cancer to one of two radiation regimens: conventional (tangential field) fractionated whole breast treatment or accelerated partial breast irradiation plus intensity-modulated radiotherapy.

Michele G. Sullivan/Frontline Medical News

The patients were highly selected, with a primary tumor size of less than 25 mm and negative surgical margins of more than 5 mm, said Dr. Livi, a radiation oncologist at the University of Florence, Italy.

The cohort comprised 520 women. Most (about 85%) were node-negative; 95% of the tumors were estrogen receptor–positive, and 90% were progesterone receptor–positive. The most frequent molecular subtype was luminal A (about 75%); less than 5% were triple-negative.

The median follow-up for this portion of the study was 5 years. There were six ipsilateral breast tumor recurrences – three in each group. There were three local relapses, all in the whole breast irradiation group. The 5-year recurrence rate was 1.4% in the whole breast irradiation group and 1.5% in the partial breast irradiation group. The mean time to ipsilateral breast recurrence was 3 years, and there was no significant between-group difference in this timing.

There were 10 contralateral recurrences (seven in the whole breast group vs. three in the partial irradiation group). Distant metastases occurred in seven patients (four and three, respectively).

The 5-year overall survival rate was excellent, Dr. Livi noted: 97% in the whole breast irradiation group and 99% in the partial irradiation group.

Skin toxicity of any grade was significantly less common in the partial group (49 vs. 181). Significantly more patients in the partial irradiation group were completely free of adverse events (197 vs. 93). There were no grade 3 adverse events in either group. Two women in the whole breast irradiation group experienced a grade 2 toxicity- both of these were skin fibrosis.

Almost all patients (90%) reported good or excellent cosmetic results.

Dr. Livi fielded a few questions during the discussion period, one of which dealt with the cost of partial irradiation treatment. Since the procedure is more expensive, and the results similar, the discussant wondered whether it would be worth the additional cost. Dr Livi said the question is difficult for him to answer, because Italy’s national health care system does not charge patients for the treatment. He did say reimbursement for the treatments differs, but he did not elaborate.

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN ANTONIO – An accelerated course of partial breast irradiation was as effective as whole breast irradiation for women with early breast cancer, with significantly fewer adverse events.

The technique may be a suitable alternative for select patients who wish to minimize side effects without compromising clinical outcomes, Dr. Lorenzo Livi said at the San Antonio Breast Cancer Symposium.

He reported the 5-year results of an Italian study that randomized women with early breast cancer to one of two radiation regimens: conventional (tangential field) fractionated whole breast treatment or accelerated partial breast irradiation plus intensity-modulated radiotherapy.

Michele G. Sullivan/Frontline Medical News

The patients were highly selected, with a primary tumor size of less than 25 mm and negative surgical margins of more than 5 mm, said Dr. Livi, a radiation oncologist at the University of Florence, Italy.

The cohort comprised 520 women. Most (about 85%) were node-negative; 95% of the tumors were estrogen receptor–positive, and 90% were progesterone receptor–positive. The most frequent molecular subtype was luminal A (about 75%); less than 5% were triple-negative.

The median follow-up for this portion of the study was 5 years. There were six ipsilateral breast tumor recurrences – three in each group. There were three local relapses, all in the whole breast irradiation group. The 5-year recurrence rate was 1.4% in the whole breast irradiation group and 1.5% in the partial breast irradiation group. The mean time to ipsilateral breast recurrence was 3 years, and there was no significant between-group difference in this timing.

There were 10 contralateral recurrences (seven in the whole breast group vs. three in the partial irradiation group). Distant metastases occurred in seven patients (four and three, respectively).

The 5-year overall survival rate was excellent, Dr. Livi noted: 97% in the whole breast irradiation group and 99% in the partial irradiation group.

Skin toxicity of any grade was significantly less common in the partial group (49 vs. 181). Significantly more patients in the partial irradiation group were completely free of adverse events (197 vs. 93). There were no grade 3 adverse events in either group. Two women in the whole breast irradiation group experienced a grade 2 toxicity- both of these were skin fibrosis.

Almost all patients (90%) reported good or excellent cosmetic results.

Dr. Livi fielded a few questions during the discussion period, one of which dealt with the cost of partial irradiation treatment. Since the procedure is more expensive, and the results similar, the discussant wondered whether it would be worth the additional cost. Dr Livi said the question is difficult for him to answer, because Italy’s national health care system does not charge patients for the treatment. He did say reimbursement for the treatments differs, but he did not elaborate.

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN ANTONIO – Annual health care costs and utilization jump several-fold in nonelderly breast cancer survivors with concomitant depression, according to an analysis from the U.S. military health system.

Analysis of the records of 2,851 breast cancer survivors whose care is provided by the Department of Defense military health system indicated that 15.9% were diagnosed with depression in the time interval within 1 year prior to and 2 years after their cancer diagnosis. These dual-diagnosis patients averaged $15,471 annually in health care costs covering inpatient and outpatient services and outpatient prescriptions in the first years after being diagnosed with breast cancer, compared with $8,297 per year in those without a diagnosis of depression, Diana D. Jeffery, Ph.D., reported at the San Antonio Breast Cancer Symposium.

The mean annual number of hospital admissions was tripled: 0.33 in breast cancer survivors with depression and 0.11 in survivors without depression. The dual-diagosis group averaged 1.94 hospital bed days annually, compared with 0.58 in breast cancer survivors without depression. Breast cancer survivors diagnosed with depression averaged 28 outpatient visits annually, while those without depression averaged 16.5, according to Dr. Jeffery, a senior researcher at the Defense Health Agency in Falls Church, Va.

Fifty percent of the breast cancer survivors were diagnosed with hypertension, making this the most common chronic comorbid condition. A diagnosis of depression, anxiety, adjustment, or stress disorder was present in 37.5% of the breast cancer survivors, making this group of psychiatric diagnoses the second most prevalent comorbidity. Twenty-three percent of the breast cancer survivors had received a diagnosis of heart disease, 20% had diabetes, 16% had asthma or chronic obstructive pulmonary disease, and 17% were obese. No demographic characteristics proved predictive of an increased likelihood of being diagnosed with depression, she said.

Of note, nearly one-half of the patients with depression had been diagnosed with the affective disorder during the year prior to receiving their breast cancer diagnosis.

Dr. Jeffery said that, while these data on health care costs and utilization in breast cancer survivors with concomitant depression are likely to be of particular interest to health plans, they also show what is likely to happen following adoption of the American Society of Clinical Oncology 2014 guidelines on screening and care of depression and anxiety in adults with cancer.

The guidelines recommend that all cancer patients and cancer survivors periodically be evaluated for symptoms of depression and anxiety using validated measures across the trajectory of care to “reduce the human cost of cancer” (J. Clin. Oncol. 2014;32:1605-19).

Adoption of the depression screening guidelines will likely increase the number of breast cancer survivors with a mental health diagnosis, which, as Dr. Jeffery’s study demonstrates, will boost health care costs and utilization. On the other hand, identifying and intervening effectively in patients with mild symptoms that haven’t yet risen to the level that meets diagnostic criteria for clinical depression should yield cost savings as well as quality-of-life benefits, she added.

The Department of Defense military health system, under a health plan known as Tricare, serves 9.5 million beneficiaries in 360 military treatment clinics worldwide. It’s a system with very few restrictions upon medical-ordered cancer follow-up care, according to Dr. Jeffery.

She reported having no financial conflicts regarding this study.

bjancin@frontlinemedcom.com

SAN ANTONIO – Annual health care costs and utilization jump several-fold in nonelderly breast cancer survivors with concomitant depression, according to an analysis from the U.S. military health system.

Analysis of the records of 2,851 breast cancer survivors whose care is provided by the Department of Defense military health system indicated that 15.9% were diagnosed with depression in the time interval within 1 year prior to and 2 years after their cancer diagnosis. These dual-diagnosis patients averaged $15,471 annually in health care costs covering inpatient and outpatient services and outpatient prescriptions in the first years after being diagnosed with breast cancer, compared with $8,297 per year in those without a diagnosis of depression, Diana D. Jeffery, Ph.D., reported at the San Antonio Breast Cancer Symposium.

The mean annual number of hospital admissions was tripled: 0.33 in breast cancer survivors with depression and 0.11 in survivors without depression. The dual-diagosis group averaged 1.94 hospital bed days annually, compared with 0.58 in breast cancer survivors without depression. Breast cancer survivors diagnosed with depression averaged 28 outpatient visits annually, while those without depression averaged 16.5, according to Dr. Jeffery, a senior researcher at the Defense Health Agency in Falls Church, Va.

Fifty percent of the breast cancer survivors were diagnosed with hypertension, making this the most common chronic comorbid condition. A diagnosis of depression, anxiety, adjustment, or stress disorder was present in 37.5% of the breast cancer survivors, making this group of psychiatric diagnoses the second most prevalent comorbidity. Twenty-three percent of the breast cancer survivors had received a diagnosis of heart disease, 20% had diabetes, 16% had asthma or chronic obstructive pulmonary disease, and 17% were obese. No demographic characteristics proved predictive of an increased likelihood of being diagnosed with depression, she said.

Of note, nearly one-half of the patients with depression had been diagnosed with the affective disorder during the year prior to receiving their breast cancer diagnosis.

Dr. Jeffery said that, while these data on health care costs and utilization in breast cancer survivors with concomitant depression are likely to be of particular interest to health plans, they also show what is likely to happen following adoption of the American Society of Clinical Oncology 2014 guidelines on screening and care of depression and anxiety in adults with cancer.

The guidelines recommend that all cancer patients and cancer survivors periodically be evaluated for symptoms of depression and anxiety using validated measures across the trajectory of care to “reduce the human cost of cancer” (J. Clin. Oncol. 2014;32:1605-19).

Adoption of the depression screening guidelines will likely increase the number of breast cancer survivors with a mental health diagnosis, which, as Dr. Jeffery’s study demonstrates, will boost health care costs and utilization. On the other hand, identifying and intervening effectively in patients with mild symptoms that haven’t yet risen to the level that meets diagnostic criteria for clinical depression should yield cost savings as well as quality-of-life benefits, she added.

The Department of Defense military health system, under a health plan known as Tricare, serves 9.5 million beneficiaries in 360 military treatment clinics worldwide. It’s a system with very few restrictions upon medical-ordered cancer follow-up care, according to Dr. Jeffery.

She reported having no financial conflicts regarding this study.

bjancin@frontlinemedcom.com

SAN ANTONIO – Annual health care costs and utilization jump several-fold in nonelderly breast cancer survivors with concomitant depression, according to an analysis from the U.S. military health system.

Analysis of the records of 2,851 breast cancer survivors whose care is provided by the Department of Defense military health system indicated that 15.9% were diagnosed with depression in the time interval within 1 year prior to and 2 years after their cancer diagnosis. These dual-diagnosis patients averaged $15,471 annually in health care costs covering inpatient and outpatient services and outpatient prescriptions in the first years after being diagnosed with breast cancer, compared with $8,297 per year in those without a diagnosis of depression, Diana D. Jeffery, Ph.D., reported at the San Antonio Breast Cancer Symposium.

The mean annual number of hospital admissions was tripled: 0.33 in breast cancer survivors with depression and 0.11 in survivors without depression. The dual-diagosis group averaged 1.94 hospital bed days annually, compared with 0.58 in breast cancer survivors without depression. Breast cancer survivors diagnosed with depression averaged 28 outpatient visits annually, while those without depression averaged 16.5, according to Dr. Jeffery, a senior researcher at the Defense Health Agency in Falls Church, Va.

Fifty percent of the breast cancer survivors were diagnosed with hypertension, making this the most common chronic comorbid condition. A diagnosis of depression, anxiety, adjustment, or stress disorder was present in 37.5% of the breast cancer survivors, making this group of psychiatric diagnoses the second most prevalent comorbidity. Twenty-three percent of the breast cancer survivors had received a diagnosis of heart disease, 20% had diabetes, 16% had asthma or chronic obstructive pulmonary disease, and 17% were obese. No demographic characteristics proved predictive of an increased likelihood of being diagnosed with depression, she said.

Of note, nearly one-half of the patients with depression had been diagnosed with the affective disorder during the year prior to receiving their breast cancer diagnosis.

Dr. Jeffery said that, while these data on health care costs and utilization in breast cancer survivors with concomitant depression are likely to be of particular interest to health plans, they also show what is likely to happen following adoption of the American Society of Clinical Oncology 2014 guidelines on screening and care of depression and anxiety in adults with cancer.

The guidelines recommend that all cancer patients and cancer survivors periodically be evaluated for symptoms of depression and anxiety using validated measures across the trajectory of care to “reduce the human cost of cancer” (J. Clin. Oncol. 2014;32:1605-19).

Adoption of the depression screening guidelines will likely increase the number of breast cancer survivors with a mental health diagnosis, which, as Dr. Jeffery’s study demonstrates, will boost health care costs and utilization. On the other hand, identifying and intervening effectively in patients with mild symptoms that haven’t yet risen to the level that meets diagnostic criteria for clinical depression should yield cost savings as well as quality-of-life benefits, she added.

The Department of Defense military health system, under a health plan known as Tricare, serves 9.5 million beneficiaries in 360 military treatment clinics worldwide. It’s a system with very few restrictions upon medical-ordered cancer follow-up care, according to Dr. Jeffery.

She reported having no financial conflicts regarding this study.

bjancin@frontlinemedcom.com

SAN ANTONIO – Adding daily everolimus to weekly trastuzumab and paclitaxel as first-line therapy resulted in a median 7.2-month gain in progression-free survival in women with hormone receptor-negative, HER2+ advanced breast cancer in the Phase III BOLERO-1 trial.

Median progression-free survival was 20.27 months with the addition of everolimus (Afinitor) compared with 13.08 months with placebo in the 309 patients with hormone receptor-negative disease who participated in the randomized, double-blind study conducted at 141 centers in 28 countries, Dr. Sara A. Hurvitz reported at the San Antonio Breast Cancer Symposium. This translated to a 34% relative risk reduction for disease progression in patients randomized to everolimus, an oral mTOR inhibitor (P = .0049). However, this seemingly robust outcome did not actually achieve statistical significance. Since this was a subgroup analysis -- the other 410 participants in BOLERO-1 had hormone receptor-positive, HER2+ advanced breast cancer -- the prespecified threshold for significance set by the study statisticians for the analysis in hormone receptor-negative patients was P = .0044.

An Australian statistician rose from the audience to take issue with the BOLERO-1 statisticians in setting the bar for statistical significance so high.

“This was a statistical decision that was made. We’re all thinking about that,” admitted Dr. Hurvitz, director of the breast oncology program in the division of hematology-oncology at the University of California, Los Angeles.

Everolimus showed no benefit in the full study population, where median progression-free survival was virtually identical in the two treatment arms: 14.95 months with everolimus at 10 mg daily, 14.49 months with placebo.

Trastuzumab (Herceptin) has dramatically improved outcomes in patients diagnosed with HER2+ breast cancer, both in the early-stage and advanced settings. But not everyone benefits.

“Resistance to treatment remains a major clinical unmet challenge,” she observed.

The rationale for BOLERO-1 was that hyperactivation of the P13 kinase/mTOR pathway is one likely mechanism for HER2 resistance, and therefore an mTOR inhibitor such as everolimus might close off this resistance.

The most common adverse events associated with everolimus in BOLERO-1 were stomatitis, diarrhea, neutropenia, and anemia.

Of greater concern was the 3.6% mortality due to adverse events in the everolimus group compared with none in placebo-treated controls. Most of the deaths were due to pulmonary causes. Study leaders noticed that these deaths were occurring in centers with little experience in using everolimus. A letter was sent to all investigators underscoring the need for proactive aggressive management of adverse events in patients taking everolimus with chemotherapy; after that there was only a single additional death.

Dr. C. Kent Osborne commented that he thought it was a mistake for the BOLERO-1 investigators not to allow endocrine therapy in the patients with hormone receptor-positive disease.

“I think it’s important to add endocrine therapy because the estrogen receptor provides an immediate escape mechanism. If you don’t block it in a HER2+ tumor, the estrogen receptor can start activating and signaling the tumor cell to survive. It’s a very important issue,” said Dr. Osborne, professor of medicine and director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

Dr. Hurvitz concurred.

“Now, with our retrospectoscope on, I think ongoing and future studies are going to be utilizing endocrine therapy with HER2-targeted therapy and P13 kinase inhibitors in this setting,” the oncologist said.

The BOLERO-1 trial was sponsored by Novartis. Dr. Hurvitz reported receiving research support from Genentech, Roche, and Novartis.

bjancin@frontlinemedcom.com

SAN ANTONIO – Adding daily everolimus to weekly trastuzumab and paclitaxel as first-line therapy resulted in a median 7.2-month gain in progression-free survival in women with hormone receptor-negative, HER2+ advanced breast cancer in the Phase III BOLERO-1 trial.

Median progression-free survival was 20.27 months with the addition of everolimus (Afinitor) compared with 13.08 months with placebo in the 309 patients with hormone receptor-negative disease who participated in the randomized, double-blind study conducted at 141 centers in 28 countries, Dr. Sara A. Hurvitz reported at the San Antonio Breast Cancer Symposium. This translated to a 34% relative risk reduction for disease progression in patients randomized to everolimus, an oral mTOR inhibitor (P = .0049). However, this seemingly robust outcome did not actually achieve statistical significance. Since this was a subgroup analysis -- the other 410 participants in BOLERO-1 had hormone receptor-positive, HER2+ advanced breast cancer -- the prespecified threshold for significance set by the study statisticians for the analysis in hormone receptor-negative patients was P = .0044.

An Australian statistician rose from the audience to take issue with the BOLERO-1 statisticians in setting the bar for statistical significance so high.

“This was a statistical decision that was made. We’re all thinking about that,” admitted Dr. Hurvitz, director of the breast oncology program in the division of hematology-oncology at the University of California, Los Angeles.

Everolimus showed no benefit in the full study population, where median progression-free survival was virtually identical in the two treatment arms: 14.95 months with everolimus at 10 mg daily, 14.49 months with placebo.

Trastuzumab (Herceptin) has dramatically improved outcomes in patients diagnosed with HER2+ breast cancer, both in the early-stage and advanced settings. But not everyone benefits.

“Resistance to treatment remains a major clinical unmet challenge,” she observed.

The rationale for BOLERO-1 was that hyperactivation of the P13 kinase/mTOR pathway is one likely mechanism for HER2 resistance, and therefore an mTOR inhibitor such as everolimus might close off this resistance.

The most common adverse events associated with everolimus in BOLERO-1 were stomatitis, diarrhea, neutropenia, and anemia.

Of greater concern was the 3.6% mortality due to adverse events in the everolimus group compared with none in placebo-treated controls. Most of the deaths were due to pulmonary causes. Study leaders noticed that these deaths were occurring in centers with little experience in using everolimus. A letter was sent to all investigators underscoring the need for proactive aggressive management of adverse events in patients taking everolimus with chemotherapy; after that there was only a single additional death.

Dr. C. Kent Osborne commented that he thought it was a mistake for the BOLERO-1 investigators not to allow endocrine therapy in the patients with hormone receptor-positive disease.

“I think it’s important to add endocrine therapy because the estrogen receptor provides an immediate escape mechanism. If you don’t block it in a HER2+ tumor, the estrogen receptor can start activating and signaling the tumor cell to survive. It’s a very important issue,” said Dr. Osborne, professor of medicine and director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

Dr. Hurvitz concurred.

“Now, with our retrospectoscope on, I think ongoing and future studies are going to be utilizing endocrine therapy with HER2-targeted therapy and P13 kinase inhibitors in this setting,” the oncologist said.

The BOLERO-1 trial was sponsored by Novartis. Dr. Hurvitz reported receiving research support from Genentech, Roche, and Novartis.

bjancin@frontlinemedcom.com

SAN ANTONIO – Adding daily everolimus to weekly trastuzumab and paclitaxel as first-line therapy resulted in a median 7.2-month gain in progression-free survival in women with hormone receptor-negative, HER2+ advanced breast cancer in the Phase III BOLERO-1 trial.

Median progression-free survival was 20.27 months with the addition of everolimus (Afinitor) compared with 13.08 months with placebo in the 309 patients with hormone receptor-negative disease who participated in the randomized, double-blind study conducted at 141 centers in 28 countries, Dr. Sara A. Hurvitz reported at the San Antonio Breast Cancer Symposium. This translated to a 34% relative risk reduction for disease progression in patients randomized to everolimus, an oral mTOR inhibitor (P = .0049). However, this seemingly robust outcome did not actually achieve statistical significance. Since this was a subgroup analysis -- the other 410 participants in BOLERO-1 had hormone receptor-positive, HER2+ advanced breast cancer -- the prespecified threshold for significance set by the study statisticians for the analysis in hormone receptor-negative patients was P = .0044.

An Australian statistician rose from the audience to take issue with the BOLERO-1 statisticians in setting the bar for statistical significance so high.

“This was a statistical decision that was made. We’re all thinking about that,” admitted Dr. Hurvitz, director of the breast oncology program in the division of hematology-oncology at the University of California, Los Angeles.

Everolimus showed no benefit in the full study population, where median progression-free survival was virtually identical in the two treatment arms: 14.95 months with everolimus at 10 mg daily, 14.49 months with placebo.

Trastuzumab (Herceptin) has dramatically improved outcomes in patients diagnosed with HER2+ breast cancer, both in the early-stage and advanced settings. But not everyone benefits.

“Resistance to treatment remains a major clinical unmet challenge,” she observed.

The rationale for BOLERO-1 was that hyperactivation of the P13 kinase/mTOR pathway is one likely mechanism for HER2 resistance, and therefore an mTOR inhibitor such as everolimus might close off this resistance.

The most common adverse events associated with everolimus in BOLERO-1 were stomatitis, diarrhea, neutropenia, and anemia.

Of greater concern was the 3.6% mortality due to adverse events in the everolimus group compared with none in placebo-treated controls. Most of the deaths were due to pulmonary causes. Study leaders noticed that these deaths were occurring in centers with little experience in using everolimus. A letter was sent to all investigators underscoring the need for proactive aggressive management of adverse events in patients taking everolimus with chemotherapy; after that there was only a single additional death.

Dr. C. Kent Osborne commented that he thought it was a mistake for the BOLERO-1 investigators not to allow endocrine therapy in the patients with hormone receptor-positive disease.

“I think it’s important to add endocrine therapy because the estrogen receptor provides an immediate escape mechanism. If you don’t block it in a HER2+ tumor, the estrogen receptor can start activating and signaling the tumor cell to survive. It’s a very important issue,” said Dr. Osborne, professor of medicine and director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

Dr. Hurvitz concurred.

“Now, with our retrospectoscope on, I think ongoing and future studies are going to be utilizing endocrine therapy with HER2-targeted therapy and P13 kinase inhibitors in this setting,” the oncologist said.

The BOLERO-1 trial was sponsored by Novartis. Dr. Hurvitz reported receiving research support from Genentech, Roche, and Novartis.

bjancin@frontlinemedcom.com

SAN ANTONIO – Losing weight and exercising may be an important key to good outcomes in some women with breast cancer – especially those with hormone receptor–negative tumors.

For women with tumors that are both estrogen and progesterone receptor negative, losing at least 5 pounds or 5% of total body weight decreased the 10-year risk of all-cause mortality by 64%, Dr. Rowan T. Chlebowski said at the San Antonio Breast Cancer Symposium.

Although it was a post hoc exploratory analysis, the subgroup findings suggest that a lifestyle intervention program could be an effective way to help increase a woman’s chances of surviving, said Dr. Chlebowski, chief of medical oncology at the UCLA Medical Center, Los Angeles.

“From a scientific standpoint, others will have to look at this post hoc analysis and decide whether the data warrant further investigation in a trial to confirm the findings,” he said. “But, on an operational basis, for a woman with breast cancer, there are so many other health benefits associated with this kind of weight loss. For example, this has been shown to significantly reduce the risk of progression from prediabetes to diabetes – and that is a very important health consideration for women with breast cancer.”

And obviously, he added, losing weight and getting active carry a myriad of other health benefits, all of which exert their own positive influences.

Dr. Chlebowski reported long-term follow-up data from the Women’s Intervention Nutrition Study (WINS). It enrolled 2,437 women from 1994 to 2001 who had been treated for early-stage breast cancer. The women, aged 48-79 years, were randomly assigned to a lower-fat dietary intervention group or to a control group that ate their regular diet. The intervention group met monthly with a registered dietitian and provided food journals. They were also encouraged to increase physical activity.

At the start of the study, both groups consumed similar amounts of calories from fat, about 57 g/day or 30% of daily caloric intake. At the end of the first year of observation, the women in the dietary intervention group had reduced their fat intake by an average of 24 g/day, compared with only a 5-gram/day drop in the control group. The difference between the two groups was maintained throughout the trial. By the fifth year of the trial, the women in the intervention group weighed an average of 6 pounds less than did the women in the control group.

But at the current follow-up (maximum of 20 years), there was no significant between-group difference in disease-free survival (17% deaths in the control groups vs. 13.6% in the intervention group), either in the entire group or in the subgroup of those with estrogen and progesterone receptor–positive tumors.

However, in the subanalysis of those who were hormone receptor negative, the difference was significant, with a 2-year survival advantage in the intervention group (14 vs. 12 years; hazard ratio, 0.64; P = .045).

The findings may be particularly important for women with triple-negative tumors, since, Dr. Chlebowski noted, data suggest that about 73% of women with ER/PR-negative cancers are anticipated to be triple negative.

He said the protective mechanism is not entirely clear, but may be due more to total calorie decrease than to decreasing fat alone – despite fat’s proclivity to increase total estrogen levels.

“Estrogen does not seem to be the driver here,” he said. Instead, the benefit may have more to do with controlling growth factors, inflammation, and glucose levels.

He did point out that the data are a bit old, and that only 6% of women in the study received tamoxifen. But he stressed that further investigation could refine the results and that, in any case, controlling weight confers a multitude of benefits.

Dr. Chlebowski had no disclosures. The WINS study was sponsored by the National Cancer Institute.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN ANTONIO – Losing weight and exercising may be an important key to good outcomes in some women with breast cancer – especially those with hormone receptor–negative tumors.

For women with tumors that are both estrogen and progesterone receptor negative, losing at least 5 pounds or 5% of total body weight decreased the 10-year risk of all-cause mortality by 64%, Dr. Rowan T. Chlebowski said at the San Antonio Breast Cancer Symposium.

Although it was a post hoc exploratory analysis, the subgroup findings suggest that a lifestyle intervention program could be an effective way to help increase a woman’s chances of surviving, said Dr. Chlebowski, chief of medical oncology at the UCLA Medical Center, Los Angeles.

“From a scientific standpoint, others will have to look at this post hoc analysis and decide whether the data warrant further investigation in a trial to confirm the findings,” he said. “But, on an operational basis, for a woman with breast cancer, there are so many other health benefits associated with this kind of weight loss. For example, this has been shown to significantly reduce the risk of progression from prediabetes to diabetes – and that is a very important health consideration for women with breast cancer.”

And obviously, he added, losing weight and getting active carry a myriad of other health benefits, all of which exert their own positive influences.

Dr. Chlebowski reported long-term follow-up data from the Women’s Intervention Nutrition Study (WINS). It enrolled 2,437 women from 1994 to 2001 who had been treated for early-stage breast cancer. The women, aged 48-79 years, were randomly assigned to a lower-fat dietary intervention group or to a control group that ate their regular diet. The intervention group met monthly with a registered dietitian and provided food journals. They were also encouraged to increase physical activity.

At the start of the study, both groups consumed similar amounts of calories from fat, about 57 g/day or 30% of daily caloric intake. At the end of the first year of observation, the women in the dietary intervention group had reduced their fat intake by an average of 24 g/day, compared with only a 5-gram/day drop in the control group. The difference between the two groups was maintained throughout the trial. By the fifth year of the trial, the women in the intervention group weighed an average of 6 pounds less than did the women in the control group.

But at the current follow-up (maximum of 20 years), there was no significant between-group difference in disease-free survival (17% deaths in the control groups vs. 13.6% in the intervention group), either in the entire group or in the subgroup of those with estrogen and progesterone receptor–positive tumors.

However, in the subanalysis of those who were hormone receptor negative, the difference was significant, with a 2-year survival advantage in the intervention group (14 vs. 12 years; hazard ratio, 0.64; P = .045).

The findings may be particularly important for women with triple-negative tumors, since, Dr. Chlebowski noted, data suggest that about 73% of women with ER/PR-negative cancers are anticipated to be triple negative.

He said the protective mechanism is not entirely clear, but may be due more to total calorie decrease than to decreasing fat alone – despite fat’s proclivity to increase total estrogen levels.

“Estrogen does not seem to be the driver here,” he said. Instead, the benefit may have more to do with controlling growth factors, inflammation, and glucose levels.

He did point out that the data are a bit old, and that only 6% of women in the study received tamoxifen. But he stressed that further investigation could refine the results and that, in any case, controlling weight confers a multitude of benefits.

Dr. Chlebowski had no disclosures. The WINS study was sponsored by the National Cancer Institute.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN ANTONIO – Losing weight and exercising may be an important key to good outcomes in some women with breast cancer – especially those with hormone receptor–negative tumors.

For women with tumors that are both estrogen and progesterone receptor negative, losing at least 5 pounds or 5% of total body weight decreased the 10-year risk of all-cause mortality by 64%, Dr. Rowan T. Chlebowski said at the San Antonio Breast Cancer Symposium.

Although it was a post hoc exploratory analysis, the subgroup findings suggest that a lifestyle intervention program could be an effective way to help increase a woman’s chances of surviving, said Dr. Chlebowski, chief of medical oncology at the UCLA Medical Center, Los Angeles.

“From a scientific standpoint, others will have to look at this post hoc analysis and decide whether the data warrant further investigation in a trial to confirm the findings,” he said. “But, on an operational basis, for a woman with breast cancer, there are so many other health benefits associated with this kind of weight loss. For example, this has been shown to significantly reduce the risk of progression from prediabetes to diabetes – and that is a very important health consideration for women with breast cancer.”

And obviously, he added, losing weight and getting active carry a myriad of other health benefits, all of which exert their own positive influences.

Dr. Chlebowski reported long-term follow-up data from the Women’s Intervention Nutrition Study (WINS). It enrolled 2,437 women from 1994 to 2001 who had been treated for early-stage breast cancer. The women, aged 48-79 years, were randomly assigned to a lower-fat dietary intervention group or to a control group that ate their regular diet. The intervention group met monthly with a registered dietitian and provided food journals. They were also encouraged to increase physical activity.

At the start of the study, both groups consumed similar amounts of calories from fat, about 57 g/day or 30% of daily caloric intake. At the end of the first year of observation, the women in the dietary intervention group had reduced their fat intake by an average of 24 g/day, compared with only a 5-gram/day drop in the control group. The difference between the two groups was maintained throughout the trial. By the fifth year of the trial, the women in the intervention group weighed an average of 6 pounds less than did the women in the control group.

But at the current follow-up (maximum of 20 years), there was no significant between-group difference in disease-free survival (17% deaths in the control groups vs. 13.6% in the intervention group), either in the entire group or in the subgroup of those with estrogen and progesterone receptor–positive tumors.

However, in the subanalysis of those who were hormone receptor negative, the difference was significant, with a 2-year survival advantage in the intervention group (14 vs. 12 years; hazard ratio, 0.64; P = .045).

The findings may be particularly important for women with triple-negative tumors, since, Dr. Chlebowski noted, data suggest that about 73% of women with ER/PR-negative cancers are anticipated to be triple negative.

He said the protective mechanism is not entirely clear, but may be due more to total calorie decrease than to decreasing fat alone – despite fat’s proclivity to increase total estrogen levels.

“Estrogen does not seem to be the driver here,” he said. Instead, the benefit may have more to do with controlling growth factors, inflammation, and glucose levels.

He did point out that the data are a bit old, and that only 6% of women in the study received tamoxifen. But he stressed that further investigation could refine the results and that, in any case, controlling weight confers a multitude of benefits.

Dr. Chlebowski had no disclosures. The WINS study was sponsored by the National Cancer Institute.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN ANTONIO – The Oncology Report associate editors Dr. William J. Gradishar and Dr. Hope S. Rugo discuss highlights presented at the 2014 San Antonio Breast Cancer Symposium.

First reports on checkpoint inhibitors for the treatment of breast cancer, the unique study issues to consider in investigating these immunotherapy options, disappointing results from the FERGI trial, which looked at a combination therapy with a PI3 kinase inhibitor, and overall survival data from the FIRST trial of endocrine therapy with fulvestrant for patients with advanced disease were some of the topics Dr. Gradishar and Dr. Rugo weighed in on during the discussion.

The TNT trial comparing carboplatin to docetaxel in treating patients with triple-negative breast cancer; the latest results from the SOFT trial, looking at ovarian suppression in combination with either an aromatase inhibitor or tamoxifen; and the mixed results from BOLERO-1 looking at the addition of an mTOR inhibitor to the treatment of patients with advanced HER2-positive disease were also discussed.

Dr. Gradishar is the Betsy Bramsen Professor of Breast Oncology at the Northwestern University, Chicago. Dr. Rugo is a professor of medicine, University of California, San Francisco, and director, breast oncology and clinical trials education, UCSF Helen Diller Family Comprehensive Cancer Center.

SAN ANTONIO – The Oncology Report associate editors Dr. William J. Gradishar and Dr. Hope S. Rugo discuss highlights presented at the 2014 San Antonio Breast Cancer Symposium.

First reports on checkpoint inhibitors for the treatment of breast cancer, the unique study issues to consider in investigating these immunotherapy options, disappointing results from the FERGI trial, which looked at a combination therapy with a PI3 kinase inhibitor, and overall survival data from the FIRST trial of endocrine therapy with fulvestrant for patients with advanced disease were some of the topics Dr. Gradishar and Dr. Rugo weighed in on during the discussion.

The TNT trial comparing carboplatin to docetaxel in treating patients with triple-negative breast cancer; the latest results from the SOFT trial, looking at ovarian suppression in combination with either an aromatase inhibitor or tamoxifen; and the mixed results from BOLERO-1 looking at the addition of an mTOR inhibitor to the treatment of patients with advanced HER2-positive disease were also discussed.

Dr. Gradishar is the Betsy Bramsen Professor of Breast Oncology at the Northwestern University, Chicago. Dr. Rugo is a professor of medicine, University of California, San Francisco, and director, breast oncology and clinical trials education, UCSF Helen Diller Family Comprehensive Cancer Center.

SAN ANTONIO – The Oncology Report associate editors Dr. William J. Gradishar and Dr. Hope S. Rugo discuss highlights presented at the 2014 San Antonio Breast Cancer Symposium.

First reports on checkpoint inhibitors for the treatment of breast cancer, the unique study issues to consider in investigating these immunotherapy options, disappointing results from the FERGI trial, which looked at a combination therapy with a PI3 kinase inhibitor, and overall survival data from the FIRST trial of endocrine therapy with fulvestrant for patients with advanced disease were some of the topics Dr. Gradishar and Dr. Rugo weighed in on during the discussion.

The TNT trial comparing carboplatin to docetaxel in treating patients with triple-negative breast cancer; the latest results from the SOFT trial, looking at ovarian suppression in combination with either an aromatase inhibitor or tamoxifen; and the mixed results from BOLERO-1 looking at the addition of an mTOR inhibitor to the treatment of patients with advanced HER2-positive disease were also discussed.

Dr. Gradishar is the Betsy Bramsen Professor of Breast Oncology at the Northwestern University, Chicago. Dr. Rugo is a professor of medicine, University of California, San Francisco, and director, breast oncology and clinical trials education, UCSF Helen Diller Family Comprehensive Cancer Center.

SAN ANTONIO – Fulvestrant resulted in a 30% improvement in overall survival, compared with anastrozole as first-line therapy for postmenopausal women with hormone receptor–positive advanced or metastatic breast cancer in the randomized FIRST trial.

This new finding follows upon a previously reported 34% reduction in the risk of disease progression in an earlier FIRST analysis. Plus, significant improvements in both disease progression and overall survival were seen with fulvestrant at 500 mg as second-line endocrine therapy in the Phase III CONFIRM (Comparison of Faslodex in Recurrent or Metastatic Breast Cancer) trial (J. Natl. Cancer Inst. Jan 2014;106:djt337 [doi:10.1093/jnci/djt337]). The clinical performance of fulvestrant in these two studies outpaces that of any other endocrine therapy for advanced breast cancer, Dr. John Robertson observed in presenting the new FIRST overall survival results at the San Antonio Breast Cancer Symposium.

“I don’t know of any other endocrine therapy where you can see both a time-to-progression and overall survival benefit in both the second- and first-line settings. So I think this is a new and exciting development in endocrine therapy for women with advanced breast cancer,” declared Dr. John Robertson, professor of surgery at the University of Nottingham, England.

FIRST (Fulvestrant First-line Study Comparing Endocrine Treatments) was a phase II, open-label study involving 205 women randomized to intramuscular fulvestrant (Faslodex) at 500 mg once monthly or the aromatase inhibitor anastrozole (Arimidex) at 1 mg/day orally. Aromatase inhibitors have been considered the standard therapy in this setting.

At a median follow-up of 48.8 months, the median overall survival was 54.1 months in the fulvestrant arm, compared with 48.4 months with anastrozole, for a 5.7-month advantage in favor of fulvestrant. This translated to a 30% reduction in the risk of death in the fulvestrant group (P = .041), which Dr. Robertson believes patients and their families will consider highly clinically meaningful.

“When I first started taking care of breast cancer patients like these 30 years ago, the average survival was 24 months. In this study, with fulvestrant it’s 54 months. We’re seeing step-by-step improvements,” he commented.

The advantage in overall survival seen with fulvestrant was consistent across all predefined subgroups based upon age, prior chemotherapy or endocrine therapy, visceral involvement status, and progesterone receptor status.

Both treatments were generally well tolerated, with no new safety concerns observed.

“Fulvestrant is a drug that’s really well tolerated. I can’t think of another medication in oncology where you can double the dose – from 250 to 500 mg – with no increase in side effects,” Dr. Robertson observed.

Now underway is the phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy–Naive Advanced Breast Cancer) trial, in which 450 hormone therapy–naive women with advanced breast cancer are being randomized to fulvestrant at 500 mg or anastrozole.

Dr. C. Kent Osborne commented, “Many people, including myself, have thought since the time fulvestrant was developed in the lab that it was the best endocrine therapy that we have.” But the drug “has had a checkered past,” he noted, citing the inconvenience of the required once-monthly intramuscular injections, plus the fact that early studies of fulvestrant as adjuvant therapy in early breast cancer yielded unimpressive results because they used fulvestrant at 250 mg, which turned out to be the wrong dose.

“In view of the data from CONFIRM and FIRST, are there plans to bring fulvestrant back into the adjuvant setting?” asked Dr. Osborne, professor of medicine and director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

Dr. Robertson replied that it’s now quite apparent that fulvestrant would likely outperform aromatase inhibitors or tamoxifen as adjuvant therapy in early breast cancer, but he doubts that AstraZeneca, which markets the selective estrogen receptor down-regulator, will sponsor the requisite clinical trials. It wouldn’t be commercially viable. Adjuvant breast cancer therapy trials take a long time to produce results, and the drug will be close to going off patent by then.

“It’s a study that’s crying out to be done given what we’ve seen here in the FIRST study, but I think it is unlikely to happen unless somebody like the NIH takes on the funding,” Dr. Robertson said.

Pharmaceutical companies are now developing next-generation selective estrogen receptor down-regulators that can be given orally. They’re so new that it’s not yet known whether they’re actually effective, but if they are, they’ll be the ones studied as adjuvant therapy in clinical trials, not fulvestrant, he predicted.

“I’m skeptical,” said Dr. Osborne. “Trying to develop a better fulvestrant might work, but remember that after tamoxifen came out many, many companies tried to develop a better tamoxifen – and here we are with tamoxifen 40 years later.”

The FIRST trial was funded by AstraZeneca. Dr. Robertson reported serving as a consultant to that company as well as Bayer HealthCare and receiving research funding from both companies along with Amgen and Novartis.

bjancin@frontlinemedcom.com

SAN ANTONIO – Fulvestrant resulted in a 30% improvement in overall survival, compared with anastrozole as first-line therapy for postmenopausal women with hormone receptor–positive advanced or metastatic breast cancer in the randomized FIRST trial.

This new finding follows upon a previously reported 34% reduction in the risk of disease progression in an earlier FIRST analysis. Plus, significant improvements in both disease progression and overall survival were seen with fulvestrant at 500 mg as second-line endocrine therapy in the Phase III CONFIRM (Comparison of Faslodex in Recurrent or Metastatic Breast Cancer) trial (J. Natl. Cancer Inst. Jan 2014;106:djt337 [doi:10.1093/jnci/djt337]). The clinical performance of fulvestrant in these two studies outpaces that of any other endocrine therapy for advanced breast cancer, Dr. John Robertson observed in presenting the new FIRST overall survival results at the San Antonio Breast Cancer Symposium.

“I don’t know of any other endocrine therapy where you can see both a time-to-progression and overall survival benefit in both the second- and first-line settings. So I think this is a new and exciting development in endocrine therapy for women with advanced breast cancer,” declared Dr. John Robertson, professor of surgery at the University of Nottingham, England.

FIRST (Fulvestrant First-line Study Comparing Endocrine Treatments) was a phase II, open-label study involving 205 women randomized to intramuscular fulvestrant (Faslodex) at 500 mg once monthly or the aromatase inhibitor anastrozole (Arimidex) at 1 mg/day orally. Aromatase inhibitors have been considered the standard therapy in this setting.

At a median follow-up of 48.8 months, the median overall survival was 54.1 months in the fulvestrant arm, compared with 48.4 months with anastrozole, for a 5.7-month advantage in favor of fulvestrant. This translated to a 30% reduction in the risk of death in the fulvestrant group (P = .041), which Dr. Robertson believes patients and their families will consider highly clinically meaningful.

“When I first started taking care of breast cancer patients like these 30 years ago, the average survival was 24 months. In this study, with fulvestrant it’s 54 months. We’re seeing step-by-step improvements,” he commented.

The advantage in overall survival seen with fulvestrant was consistent across all predefined subgroups based upon age, prior chemotherapy or endocrine therapy, visceral involvement status, and progesterone receptor status.

Both treatments were generally well tolerated, with no new safety concerns observed.

“Fulvestrant is a drug that’s really well tolerated. I can’t think of another medication in oncology where you can double the dose – from 250 to 500 mg – with no increase in side effects,” Dr. Robertson observed.

Now underway is the phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy–Naive Advanced Breast Cancer) trial, in which 450 hormone therapy–naive women with advanced breast cancer are being randomized to fulvestrant at 500 mg or anastrozole.

Dr. C. Kent Osborne commented, “Many people, including myself, have thought since the time fulvestrant was developed in the lab that it was the best endocrine therapy that we have.” But the drug “has had a checkered past,” he noted, citing the inconvenience of the required once-monthly intramuscular injections, plus the fact that early studies of fulvestrant as adjuvant therapy in early breast cancer yielded unimpressive results because they used fulvestrant at 250 mg, which turned out to be the wrong dose.

“In view of the data from CONFIRM and FIRST, are there plans to bring fulvestrant back into the adjuvant setting?” asked Dr. Osborne, professor of medicine and director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

Dr. Robertson replied that it’s now quite apparent that fulvestrant would likely outperform aromatase inhibitors or tamoxifen as adjuvant therapy in early breast cancer, but he doubts that AstraZeneca, which markets the selective estrogen receptor down-regulator, will sponsor the requisite clinical trials. It wouldn’t be commercially viable. Adjuvant breast cancer therapy trials take a long time to produce results, and the drug will be close to going off patent by then.

“It’s a study that’s crying out to be done given what we’ve seen here in the FIRST study, but I think it is unlikely to happen unless somebody like the NIH takes on the funding,” Dr. Robertson said.

Pharmaceutical companies are now developing next-generation selective estrogen receptor down-regulators that can be given orally. They’re so new that it’s not yet known whether they’re actually effective, but if they are, they’ll be the ones studied as adjuvant therapy in clinical trials, not fulvestrant, he predicted.

“I’m skeptical,” said Dr. Osborne. “Trying to develop a better fulvestrant might work, but remember that after tamoxifen came out many, many companies tried to develop a better tamoxifen – and here we are with tamoxifen 40 years later.”

The FIRST trial was funded by AstraZeneca. Dr. Robertson reported serving as a consultant to that company as well as Bayer HealthCare and receiving research funding from both companies along with Amgen and Novartis.

bjancin@frontlinemedcom.com

SAN ANTONIO – Fulvestrant resulted in a 30% improvement in overall survival, compared with anastrozole as first-line therapy for postmenopausal women with hormone receptor–positive advanced or metastatic breast cancer in the randomized FIRST trial.

This new finding follows upon a previously reported 34% reduction in the risk of disease progression in an earlier FIRST analysis. Plus, significant improvements in both disease progression and overall survival were seen with fulvestrant at 500 mg as second-line endocrine therapy in the Phase III CONFIRM (Comparison of Faslodex in Recurrent or Metastatic Breast Cancer) trial (J. Natl. Cancer Inst. Jan 2014;106:djt337 [doi:10.1093/jnci/djt337]). The clinical performance of fulvestrant in these two studies outpaces that of any other endocrine therapy for advanced breast cancer, Dr. John Robertson observed in presenting the new FIRST overall survival results at the San Antonio Breast Cancer Symposium.

“I don’t know of any other endocrine therapy where you can see both a time-to-progression and overall survival benefit in both the second- and first-line settings. So I think this is a new and exciting development in endocrine therapy for women with advanced breast cancer,” declared Dr. John Robertson, professor of surgery at the University of Nottingham, England.

FIRST (Fulvestrant First-line Study Comparing Endocrine Treatments) was a phase II, open-label study involving 205 women randomized to intramuscular fulvestrant (Faslodex) at 500 mg once monthly or the aromatase inhibitor anastrozole (Arimidex) at 1 mg/day orally. Aromatase inhibitors have been considered the standard therapy in this setting.

At a median follow-up of 48.8 months, the median overall survival was 54.1 months in the fulvestrant arm, compared with 48.4 months with anastrozole, for a 5.7-month advantage in favor of fulvestrant. This translated to a 30% reduction in the risk of death in the fulvestrant group (P = .041), which Dr. Robertson believes patients and their families will consider highly clinically meaningful.

“When I first started taking care of breast cancer patients like these 30 years ago, the average survival was 24 months. In this study, with fulvestrant it’s 54 months. We’re seeing step-by-step improvements,” he commented.

The advantage in overall survival seen with fulvestrant was consistent across all predefined subgroups based upon age, prior chemotherapy or endocrine therapy, visceral involvement status, and progesterone receptor status.

Both treatments were generally well tolerated, with no new safety concerns observed.

“Fulvestrant is a drug that’s really well tolerated. I can’t think of another medication in oncology where you can double the dose – from 250 to 500 mg – with no increase in side effects,” Dr. Robertson observed.

Now underway is the phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy–Naive Advanced Breast Cancer) trial, in which 450 hormone therapy–naive women with advanced breast cancer are being randomized to fulvestrant at 500 mg or anastrozole.

Dr. C. Kent Osborne commented, “Many people, including myself, have thought since the time fulvestrant was developed in the lab that it was the best endocrine therapy that we have.” But the drug “has had a checkered past,” he noted, citing the inconvenience of the required once-monthly intramuscular injections, plus the fact that early studies of fulvestrant as adjuvant therapy in early breast cancer yielded unimpressive results because they used fulvestrant at 250 mg, which turned out to be the wrong dose.

“In view of the data from CONFIRM and FIRST, are there plans to bring fulvestrant back into the adjuvant setting?” asked Dr. Osborne, professor of medicine and director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

Dr. Robertson replied that it’s now quite apparent that fulvestrant would likely outperform aromatase inhibitors or tamoxifen as adjuvant therapy in early breast cancer, but he doubts that AstraZeneca, which markets the selective estrogen receptor down-regulator, will sponsor the requisite clinical trials. It wouldn’t be commercially viable. Adjuvant breast cancer therapy trials take a long time to produce results, and the drug will be close to going off patent by then.

“It’s a study that’s crying out to be done given what we’ve seen here in the FIRST study, but I think it is unlikely to happen unless somebody like the NIH takes on the funding,” Dr. Robertson said.

Pharmaceutical companies are now developing next-generation selective estrogen receptor down-regulators that can be given orally. They’re so new that it’s not yet known whether they’re actually effective, but if they are, they’ll be the ones studied as adjuvant therapy in clinical trials, not fulvestrant, he predicted.

“I’m skeptical,” said Dr. Osborne. “Trying to develop a better fulvestrant might work, but remember that after tamoxifen came out many, many companies tried to develop a better tamoxifen – and here we are with tamoxifen 40 years later.”

The FIRST trial was funded by AstraZeneca. Dr. Robertson reported serving as a consultant to that company as well as Bayer HealthCare and receiving research funding from both companies along with Amgen and Novartis.

bjancin@frontlinemedcom.com

Objective To identify predictors of resolution of abnormal cancer screening tests in patients who received navigation.

Methods We examined data on patients with abnormal breast (n = 256) or cervical (n = 150) screening tests or symptoms who received navigation as part of the Ohio Patient Navigator Research Program during 2007-2010. We used multivariable Cox proportional hazards regression models to identify predictors of time to resolution (ie, when a patient’s clinical abnormality or abnormal screening test was determined to be a benign condition or a cancer diagnosis).

Results The median time to resolution was 183 days for navigated patients with breast abnormalities and 172 days for navigated patients with cervical abnormalities. In patients with breast abnormalities, those who reported at least 1 barrier to care during navigation (HR, 0.66; 95% CI, 0.51-0.86) or higher perceived stress (HR, 0.90; 95% CI, 0.82-0.98) had slower resolution. Among patients with cervical abnormalities, those who reported at least 1 barrier to care during navigation had slower resolution (HR, 0.62; 95% CI, 0.42-0.91). Patients with cervical abnormalities had faster resolution if they had private health insurance, but this effect was present only in younger women (interaction P = .003).

Limitations Unknown generalizability of results because patients were female and from clinics in central Ohio.

Conclusions Several variables predicted whether patient navigation led to faster resolution, and predictors differed somewhat by disease site. Results will be useful in improving current patient navigation programs and designing future programs.

Funding American Cancer Society and the National Institutes of Health 

Objective To identify predictors of resolution of abnormal cancer screening tests in patients who received navigation.

Methods We examined data on patients with abnormal breast (n = 256) or cervical (n = 150) screening tests or symptoms who received navigation as part of the Ohio Patient Navigator Research Program during 2007-2010. We used multivariable Cox proportional hazards regression models to identify predictors of time to resolution (ie, when a patient’s clinical abnormality or abnormal screening test was determined to be a benign condition or a cancer diagnosis).

Results The median time to resolution was 183 days for navigated patients with breast abnormalities and 172 days for navigated patients with cervical abnormalities. In patients with breast abnormalities, those who reported at least 1 barrier to care during navigation (HR, 0.66; 95% CI, 0.51-0.86) or higher perceived stress (HR, 0.90; 95% CI, 0.82-0.98) had slower resolution. Among patients with cervical abnormalities, those who reported at least 1 barrier to care during navigation had slower resolution (HR, 0.62; 95% CI, 0.42-0.91). Patients with cervical abnormalities had faster resolution if they had private health insurance, but this effect was present only in younger women (interaction P = .003).

Limitations Unknown generalizability of results because patients were female and from clinics in central Ohio.

Conclusions Several variables predicted whether patient navigation led to faster resolution, and predictors differed somewhat by disease site. Results will be useful in improving current patient navigation programs and designing future programs.

Funding American Cancer Society and the National Institutes of Health 

Objective To identify predictors of resolution of abnormal cancer screening tests in patients who received navigation.

Methods We examined data on patients with abnormal breast (n = 256) or cervical (n = 150) screening tests or symptoms who received navigation as part of the Ohio Patient Navigator Research Program during 2007-2010. We used multivariable Cox proportional hazards regression models to identify predictors of time to resolution (ie, when a patient’s clinical abnormality or abnormal screening test was determined to be a benign condition or a cancer diagnosis).

Results The median time to resolution was 183 days for navigated patients with breast abnormalities and 172 days for navigated patients with cervical abnormalities. In patients with breast abnormalities, those who reported at least 1 barrier to care during navigation (HR, 0.66; 95% CI, 0.51-0.86) or higher perceived stress (HR, 0.90; 95% CI, 0.82-0.98) had slower resolution. Among patients with cervical abnormalities, those who reported at least 1 barrier to care during navigation had slower resolution (HR, 0.62; 95% CI, 0.42-0.91). Patients with cervical abnormalities had faster resolution if they had private health insurance, but this effect was present only in younger women (interaction P = .003).

Limitations Unknown generalizability of results because patients were female and from clinics in central Ohio.

Conclusions Several variables predicted whether patient navigation led to faster resolution, and predictors differed somewhat by disease site. Results will be useful in improving current patient navigation programs and designing future programs.

Funding American Cancer Society and the National Institutes of Health 

Objective To examine the experiences of CABCS to better understand their information and communication needs and their preferences for survivorship care plans (SCPs).

Methods 16 CABCS, aged 37-72 years, were recruited through community-based organizations in the Northeast United States to participate in one-on-one telephone interviews about their breast cancer survivorship experience. The semistructured interviews were conducted in Mandarin, Cantonese, or English. Two investigators transcribed and translated the audio recordings into English and analyzed the interview transcripts using established methods of qualitative content analysis.

Results Three main themes were identified through analysis of interview transcripts: the need for evidence-based and culturally and linguistically appropriate health information; the role of language or communication barriers and culture in accessing care and communicating with providers; and preferences for SCP elements and format.

Limitations The sample may not be representative of the entire population of CABCS.

Conclusions The findings provide insight into the information and communication needs and SCP preferences of CABCS. Understanding the cultural nuances that underlie these needs and preferences is critical for improving CABCS’s quality of life after treatment for cancer. SCPs that incorporate Chinese-language resources and address the unique cultural needs of this population should be developed and they should include information about diet and nutrition as well as traditional Chinese medicine.

Funding This work was supported in part by the NIH-NCI’s Community Network Program Center, ACCHDC (U54CA153513, PI: Dr Grace Ma) and P30 CA06927. 

Objective To examine the experiences of CABCS to better understand their information and communication needs and their preferences for survivorship care plans (SCPs).

Methods 16 CABCS, aged 37-72 years, were recruited through community-based organizations in the Northeast United States to participate in one-on-one telephone interviews about their breast cancer survivorship experience. The semistructured interviews were conducted in Mandarin, Cantonese, or English. Two investigators transcribed and translated the audio recordings into English and analyzed the interview transcripts using established methods of qualitative content analysis.

Results Three main themes were identified through analysis of interview transcripts: the need for evidence-based and culturally and linguistically appropriate health information; the role of language or communication barriers and culture in accessing care and communicating with providers; and preferences for SCP elements and format.

Limitations The sample may not be representative of the entire population of CABCS.

Conclusions The findings provide insight into the information and communication needs and SCP preferences of CABCS. Understanding the cultural nuances that underlie these needs and preferences is critical for improving CABCS’s quality of life after treatment for cancer. SCPs that incorporate Chinese-language resources and address the unique cultural needs of this population should be developed and they should include information about diet and nutrition as well as traditional Chinese medicine.

Funding This work was supported in part by the NIH-NCI’s Community Network Program Center, ACCHDC (U54CA153513, PI: Dr Grace Ma) and P30 CA06927. 

Objective To examine the experiences of CABCS to better understand their information and communication needs and their preferences for survivorship care plans (SCPs).

Methods 16 CABCS, aged 37-72 years, were recruited through community-based organizations in the Northeast United States to participate in one-on-one telephone interviews about their breast cancer survivorship experience. The semistructured interviews were conducted in Mandarin, Cantonese, or English. Two investigators transcribed and translated the audio recordings into English and analyzed the interview transcripts using established methods of qualitative content analysis.

Results Three main themes were identified through analysis of interview transcripts: the need for evidence-based and culturally and linguistically appropriate health information; the role of language or communication barriers and culture in accessing care and communicating with providers; and preferences for SCP elements and format.

Limitations The sample may not be representative of the entire population of CABCS.

Conclusions The findings provide insight into the information and communication needs and SCP preferences of CABCS. Understanding the cultural nuances that underlie these needs and preferences is critical for improving CABCS’s quality of life after treatment for cancer. SCPs that incorporate Chinese-language resources and address the unique cultural needs of this population should be developed and they should include information about diet and nutrition as well as traditional Chinese medicine.

Funding This work was supported in part by the NIH-NCI’s Community Network Program Center, ACCHDC (U54CA153513, PI: Dr Grace Ma) and P30 CA06927. 

SAN ANTONIO – A genetic assay specific for ductal cancer in situ accurately predicted 10-year recurrence risk in women who underwent breast-conserving surgery as treatment for the disease.

Women whom the test identified as having a high recurrence risk were 68% more likely to have an ipsilateral recurrence of either ductal cancer in situ (DCIS) or invasive breast cancer, Dr. Eileen Rakovitch said at the San Antonio Breast Cancer Symposium. These results suggest that the Oncotype DX DCIS Score could be used as a risk stratification biomarker, said Dr. Rakovitch, a radiation oncologist at Sunnybrook Health Sciences Centre, Toronto.

“We hope this will enable both clinicians and patients to understand their individual risk of progression, and to weigh the risks and benefits of available treatment. This might reduce the problems of overtreating women at low risk and undertreating women at high risk of recurrence.”

The Oncotype DX DCIS is a multigene expression assay that identifies 12 of the 21 genes included in the Oncotype DX Recurrence Score; seven of these are cancer specific and five are reference genes. It stratifies women into three 10-year risk groups according to increasing score (1-100): low-risk (less than 39), intermediate risk (39-54), and high-risk (55 and higher).

It was previously validated in a retrospective analysis of 327 selected cases, all of which were estrogen receptor–positive. In that study, all women had DCIS treatment by breast-conserving surgery alone. Tumors had to be 2.5 cm or less with nuclear grades 1 or 2; or at least 1 cm with a nuclear grade 3. Negative surgical margins of at least 3 cm were also required. In that population, after adjustment for tamoxifen use, the intermediate- and high-risk groups faced more than a doubling of the 10-year ipsilateral local recurrence risk (HR 2.31) compared to the low-risk group.

The study Dr. Rakovitch reported investigated the score’s validity in a cohort with mixed hormone receptor status, and in the subgroup of women with only ER-positive tumors.

The cohort was drawn from several Canadian health care databases that linked diagnosis, treatment, and outcome. Cases were verified by chart reviews of each stage of care. The women were treated from 1994 to 2003 and followed for a mean of 10 years. The final diagnosis was DCIS, and they were treated only with breast-conserving surgery.

Most (81%) were at least 50 years old. About half had an intermediate nuclear grade; it was low in 10% and high in the remainder. Necrosis was present in 61% of the tumors; 63% were solid and 20%, multifocal. Tumor size data were missing in about half; of those with data, 25% were 10 mm or smaller and the remainder larger than 10 mm.

Over the follow-up period, there were 100 recurrences (44 DCIS and 56 invasive cancers). The overall 10-year recurrence risk was 10%. The groups diverged significantly in risk. It was 28% in the high-risk and 33% in the intermediate-risk groups – not significantly different. But both those were significantly higher than the 13% risk in the low-risk group. These results were remarkably similar to those of the earlier validity study in women with ER-positive tumors.

Risk was further stratified by whether the recurrence was local or invasive and the results were similarly significantly different. For invasive local recurrence, the risks were 15.5%, 21%, and 8% for the high-, intermediate-, and low-risk groups. For local recurrence, the risks were 13.7%, 14% and 5.4%, respectively.

A multivariate analysis controlled for age at diagnosis, tumor subtype, and multifocality – none of these were significantly related to the risk of recurrence.

Funding for the study was provided by grants from the Canadian Cancer Society Research Institute and a research grant from Genomic Health, which makes the test. Dr. Rakovitch had no conflicts of interest.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN ANTONIO – A genetic assay specific for ductal cancer in situ accurately predicted 10-year recurrence risk in women who underwent breast-conserving surgery as treatment for the disease.

Women whom the test identified as having a high recurrence risk were 68% more likely to have an ipsilateral recurrence of either ductal cancer in situ (DCIS) or invasive breast cancer, Dr. Eileen Rakovitch said at the San Antonio Breast Cancer Symposium. These results suggest that the Oncotype DX DCIS Score could be used as a risk stratification biomarker, said Dr. Rakovitch, a radiation oncologist at Sunnybrook Health Sciences Centre, Toronto.

“We hope this will enable both clinicians and patients to understand their individual risk of progression, and to weigh the risks and benefits of available treatment. This might reduce the problems of overtreating women at low risk and undertreating women at high risk of recurrence.”

The Oncotype DX DCIS is a multigene expression assay that identifies 12 of the 21 genes included in the Oncotype DX Recurrence Score; seven of these are cancer specific and five are reference genes. It stratifies women into three 10-year risk groups according to increasing score (1-100): low-risk (less than 39), intermediate risk (39-54), and high-risk (55 and higher).

It was previously validated in a retrospective analysis of 327 selected cases, all of which were estrogen receptor–positive. In that study, all women had DCIS treatment by breast-conserving surgery alone. Tumors had to be 2.5 cm or less with nuclear grades 1 or 2; or at least 1 cm with a nuclear grade 3. Negative surgical margins of at least 3 cm were also required. In that population, after adjustment for tamoxifen use, the intermediate- and high-risk groups faced more than a doubling of the 10-year ipsilateral local recurrence risk (HR 2.31) compared to the low-risk group.

The study Dr. Rakovitch reported investigated the score’s validity in a cohort with mixed hormone receptor status, and in the subgroup of women with only ER-positive tumors.

The cohort was drawn from several Canadian health care databases that linked diagnosis, treatment, and outcome. Cases were verified by chart reviews of each stage of care. The women were treated from 1994 to 2003 and followed for a mean of 10 years. The final diagnosis was DCIS, and they were treated only with breast-conserving surgery.

Most (81%) were at least 50 years old. About half had an intermediate nuclear grade; it was low in 10% and high in the remainder. Necrosis was present in 61% of the tumors; 63% were solid and 20%, multifocal. Tumor size data were missing in about half; of those with data, 25% were 10 mm or smaller and the remainder larger than 10 mm.

Over the follow-up period, there were 100 recurrences (44 DCIS and 56 invasive cancers). The overall 10-year recurrence risk was 10%. The groups diverged significantly in risk. It was 28% in the high-risk and 33% in the intermediate-risk groups – not significantly different. But both those were significantly higher than the 13% risk in the low-risk group. These results were remarkably similar to those of the earlier validity study in women with ER-positive tumors.

Risk was further stratified by whether the recurrence was local or invasive and the results were similarly significantly different. For invasive local recurrence, the risks were 15.5%, 21%, and 8% for the high-, intermediate-, and low-risk groups. For local recurrence, the risks were 13.7%, 14% and 5.4%, respectively.

A multivariate analysis controlled for age at diagnosis, tumor subtype, and multifocality – none of these were significantly related to the risk of recurrence.

Funding for the study was provided by grants from the Canadian Cancer Society Research Institute and a research grant from Genomic Health, which makes the test. Dr. Rakovitch had no conflicts of interest.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN ANTONIO – A genetic assay specific for ductal cancer in situ accurately predicted 10-year recurrence risk in women who underwent breast-conserving surgery as treatment for the disease.

Women whom the test identified as having a high recurrence risk were 68% more likely to have an ipsilateral recurrence of either ductal cancer in situ (DCIS) or invasive breast cancer, Dr. Eileen Rakovitch said at the San Antonio Breast Cancer Symposium. These results suggest that the Oncotype DX DCIS Score could be used as a risk stratification biomarker, said Dr. Rakovitch, a radiation oncologist at Sunnybrook Health Sciences Centre, Toronto.

“We hope this will enable both clinicians and patients to understand their individual risk of progression, and to weigh the risks and benefits of available treatment. This might reduce the problems of overtreating women at low risk and undertreating women at high risk of recurrence.”

The Oncotype DX DCIS is a multigene expression assay that identifies 12 of the 21 genes included in the Oncotype DX Recurrence Score; seven of these are cancer specific and five are reference genes. It stratifies women into three 10-year risk groups according to increasing score (1-100): low-risk (less than 39), intermediate risk (39-54), and high-risk (55 and higher).

It was previously validated in a retrospective analysis of 327 selected cases, all of which were estrogen receptor–positive. In that study, all women had DCIS treatment by breast-conserving surgery alone. Tumors had to be 2.5 cm or less with nuclear grades 1 or 2; or at least 1 cm with a nuclear grade 3. Negative surgical margins of at least 3 cm were also required. In that population, after adjustment for tamoxifen use, the intermediate- and high-risk groups faced more than a doubling of the 10-year ipsilateral local recurrence risk (HR 2.31) compared to the low-risk group.

The study Dr. Rakovitch reported investigated the score’s validity in a cohort with mixed hormone receptor status, and in the subgroup of women with only ER-positive tumors.

The cohort was drawn from several Canadian health care databases that linked diagnosis, treatment, and outcome. Cases were verified by chart reviews of each stage of care. The women were treated from 1994 to 2003 and followed for a mean of 10 years. The final diagnosis was DCIS, and they were treated only with breast-conserving surgery.

Most (81%) were at least 50 years old. About half had an intermediate nuclear grade; it was low in 10% and high in the remainder. Necrosis was present in 61% of the tumors; 63% were solid and 20%, multifocal. Tumor size data were missing in about half; of those with data, 25% were 10 mm or smaller and the remainder larger than 10 mm.

Over the follow-up period, there were 100 recurrences (44 DCIS and 56 invasive cancers). The overall 10-year recurrence risk was 10%. The groups diverged significantly in risk. It was 28% in the high-risk and 33% in the intermediate-risk groups – not significantly different. But both those were significantly higher than the 13% risk in the low-risk group. These results were remarkably similar to those of the earlier validity study in women with ER-positive tumors.

Risk was further stratified by whether the recurrence was local or invasive and the results were similarly significantly different. For invasive local recurrence, the risks were 15.5%, 21%, and 8% for the high-, intermediate-, and low-risk groups. For local recurrence, the risks were 13.7%, 14% and 5.4%, respectively.

A multivariate analysis controlled for age at diagnosis, tumor subtype, and multifocality – none of these were significantly related to the risk of recurrence.

Funding for the study was provided by grants from the Canadian Cancer Society Research Institute and a research grant from Genomic Health, which makes the test. Dr. Rakovitch had no conflicts of interest.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN ANTONIO – Electroacupuncture proved significantly more effective than gabapentin for treatment of hot flashes in breast cancer survivors in a randomized, placebo-controlled clinical trial.

Acupuncture was far better tolerated as well. The rate of treatment-related adverse events was higher in patients randomized to gabapentin than to women assigned to electroacupuncture, sham acupuncture, or placebo, Dr. Jun J. Mao reported at the San Antonio Breast Cancer Symposium.

The study included 120 women who had completed their primary treatment for breast cancer and were experiencing troublesome hot flashes at least twice daily. Participants were randomized to 8 weeks of treatment with electroacupuncture, sham acupuncture, gabapentin at 300 mg t.i.d., or placebo. The primary endpoint was change from baseline to week 8 in patients’ hot flash composite score as gleaned from their daily hot flash diary. The secondary endpoint was durability of response based upon the hot flash composite score at week 24, fully 4 months after patients went off treatment, explained Dr. Mao, a family physician and licensed acupuncturist at the University of Pennsylvania, Philadelphia.

From a baseline mean hot flash score of 14.3, scores dropped by a mean of 7.4 points by week 8 in the electroacupuncture recipients. This represented a significantly greater treatment effect, compared with the reductions of 5.9 points with sham acupuncture, 5.2 points with gabapentin, and 3.4 points with placebo.

Only acupuncture showed a durable treatment benefit at 24 weeks. Indeed, the magnitude of the reduction in hot flash scores 4 months after the final acupuncture session was, intriguingly, even greater than at 8 weeks, both for electroacupuncture and sham acupuncture. The mean reduction in hot flash score at 24 weeks was 8.5 points in the electroacupuncture group, as compared with 7.4 points at week 8. Sham acupuncture showed a mean 6.1-point decrease in the hot flash score at week 24, gabapentin a 4.6-point reduction, and placebo a 2.8-point drop.

No serious adverse events were noted during the study. However, 48% of gabapentin-treated patients reported treatment-related adverse events, compared with 29% on placebo, 19% who got electroacupuncture, and 3% with sham acupuncture, Dr. Mao continued.

The adherence rate to acupuncture was 90%, versus 75% with gabapentin.

Electroacupuncture entailed using a TENS unit to pass a 2-Hz current through acupuncture needles placed at traditional points. There were two sessions per week for the first 2 weeks, then once-weekly sessions for the remaining 6 weeks.

“The needle insertion is generally brief, 5-10 minutes. Then the patient rests for about 20 minutes,” according to the family physician.

Sham acupuncture utilized nonpenetrating Streitberger needles at nontraditional acupuncture points.

Discussant Dr. Michelle E. Melisko noted that this is one of the largest randomized trials of acupuncture for hot flashes ever done, and it included women of widely varied ages and a substantial African American population. It’s also the first study she’s aware of to compare acupuncture to a nonhormonal medication.

She observed that hot flashes tend to be particularly frequent, severe, and often more debilitating in breast cancer survivors than in the general population. Gabapentin (Neurontin) and venlafaxine (Effexor) are probably the two most widely prescribed centrally acting drugs for treatment of hot flashes in breast cancer survivors.

“Gabapentin is often an appealing choice. In my practice it’s a drug often used to kill two birds with one stone. It can make people sleepy, so if patients are having hot flashes and night sweats it’s nice to give them an agent they can take at bedtime that might have the dual effects of reducing hot flashes as well as improving their sleep,” said Dr. Melisko, an oncologist at the University of California, San Francisco.

She noted that a systematic review of gabapentin for hot flashes in 901 patients in seven clinical trials, including four studies in breast cancer survivors, concluded the drug resulted in 20%-30% reductions in hot flash frequency and severity, but with a dropout rate twice that for placebo (Clin. Therapeutics 2009;31:221-35).But lots of breast cancer survivors say they don’t want to take an additional side effect–laden medication to treat a different set of treatment-induced side effects, Dr. Melisko continued. They’re interested in trying complementary and alternative medicine. And while a Cochrane review has concluded that acupuncture resulted in a significant reduction in hot flash severity but not frequency (Cochrane Database Syst. Rev. 2013 July 30;7:CD007410), Dr. Melisko noted that many of the trials included in that analysis may have been too brief to give acupuncture a fair shake.

Dr. Mao agreed.

“By 4 weeks in our trial you see only about one-half of the eventual effect of electroacupuncture. So if you design a short trial you may not get to the full therapeutic dose,” he said. “With acupuncture, it’s a slow start but eventual substantial effect. I tell patients you need to give acupuncture a therapeutic trial of at least six treatments. If at that point you don’t have any benefit, it may not work for you, but if you don’t try that amount it’s suboptimal.”

In acupuncture trials across the board, whether in the setting of cancer, chronic pain, or various other conditions, roughly one-third of patients are nonresponders, according to Dr. Mao.

His study was funded by the NIH’s National Center for Complementary and Alternative Medicine. He reported having no financial conflicts.

bjancin@frontlinemedcom.com

SAN ANTONIO – Electroacupuncture proved significantly more effective than gabapentin for treatment of hot flashes in breast cancer survivors in a randomized, placebo-controlled clinical trial.

Acupuncture was far better tolerated as well. The rate of treatment-related adverse events was higher in patients randomized to gabapentin than to women assigned to electroacupuncture, sham acupuncture, or placebo, Dr. Jun J. Mao reported at the San Antonio Breast Cancer Symposium.

The study included 120 women who had completed their primary treatment for breast cancer and were experiencing troublesome hot flashes at least twice daily. Participants were randomized to 8 weeks of treatment with electroacupuncture, sham acupuncture, gabapentin at 300 mg t.i.d., or placebo. The primary endpoint was change from baseline to week 8 in patients’ hot flash composite score as gleaned from their daily hot flash diary. The secondary endpoint was durability of response based upon the hot flash composite score at week 24, fully 4 months after patients went off treatment, explained Dr. Mao, a family physician and licensed acupuncturist at the University of Pennsylvania, Philadelphia.

From a baseline mean hot flash score of 14.3, scores dropped by a mean of 7.4 points by week 8 in the electroacupuncture recipients. This represented a significantly greater treatment effect, compared with the reductions of 5.9 points with sham acupuncture, 5.2 points with gabapentin, and 3.4 points with placebo.

Only acupuncture showed a durable treatment benefit at 24 weeks. Indeed, the magnitude of the reduction in hot flash scores 4 months after the final acupuncture session was, intriguingly, even greater than at 8 weeks, both for electroacupuncture and sham acupuncture. The mean reduction in hot flash score at 24 weeks was 8.5 points in the electroacupuncture group, as compared with 7.4 points at week 8. Sham acupuncture showed a mean 6.1-point decrease in the hot flash score at week 24, gabapentin a 4.6-point reduction, and placebo a 2.8-point drop.

No serious adverse events were noted during the study. However, 48% of gabapentin-treated patients reported treatment-related adverse events, compared with 29% on placebo, 19% who got electroacupuncture, and 3% with sham acupuncture, Dr. Mao continued.

The adherence rate to acupuncture was 90%, versus 75% with gabapentin.

Electroacupuncture entailed using a TENS unit to pass a 2-Hz current through acupuncture needles placed at traditional points. There were two sessions per week for the first 2 weeks, then once-weekly sessions for the remaining 6 weeks.

“The needle insertion is generally brief, 5-10 minutes. Then the patient rests for about 20 minutes,” according to the family physician.

Sham acupuncture utilized nonpenetrating Streitberger needles at nontraditional acupuncture points.

Discussant Dr. Michelle E. Melisko noted that this is one of the largest randomized trials of acupuncture for hot flashes ever done, and it included women of widely varied ages and a substantial African American population. It’s also the first study she’s aware of to compare acupuncture to a nonhormonal medication.

She observed that hot flashes tend to be particularly frequent, severe, and often more debilitating in breast cancer survivors than in the general population. Gabapentin (Neurontin) and venlafaxine (Effexor) are probably the two most widely prescribed centrally acting drugs for treatment of hot flashes in breast cancer survivors.

“Gabapentin is often an appealing choice. In my practice it’s a drug often used to kill two birds with one stone. It can make people sleepy, so if patients are having hot flashes and night sweats it’s nice to give them an agent they can take at bedtime that might have the dual effects of reducing hot flashes as well as improving their sleep,” said Dr. Melisko, an oncologist at the University of California, San Francisco.

She noted that a systematic review of gabapentin for hot flashes in 901 patients in seven clinical trials, including four studies in breast cancer survivors, concluded the drug resulted in 20%-30% reductions in hot flash frequency and severity, but with a dropout rate twice that for placebo (Clin. Therapeutics 2009;31:221-35).But lots of breast cancer survivors say they don’t want to take an additional side effect–laden medication to treat a different set of treatment-induced side effects, Dr. Melisko continued. They’re interested in trying complementary and alternative medicine. And while a Cochrane review has concluded that acupuncture resulted in a significant reduction in hot flash severity but not frequency (Cochrane Database Syst. Rev. 2013 July 30;7:CD007410), Dr. Melisko noted that many of the trials included in that analysis may have been too brief to give acupuncture a fair shake.

Dr. Mao agreed.

“By 4 weeks in our trial you see only about one-half of the eventual effect of electroacupuncture. So if you design a short trial you may not get to the full therapeutic dose,” he said. “With acupuncture, it’s a slow start but eventual substantial effect. I tell patients you need to give acupuncture a therapeutic trial of at least six treatments. If at that point you don’t have any benefit, it may not work for you, but if you don’t try that amount it’s suboptimal.”

In acupuncture trials across the board, whether in the setting of cancer, chronic pain, or various other conditions, roughly one-third of patients are nonresponders, according to Dr. Mao.

His study was funded by the NIH’s National Center for Complementary and Alternative Medicine. He reported having no financial conflicts.

bjancin@frontlinemedcom.com

SAN ANTONIO – Electroacupuncture proved significantly more effective than gabapentin for treatment of hot flashes in breast cancer survivors in a randomized, placebo-controlled clinical trial.

Acupuncture was far better tolerated as well. The rate of treatment-related adverse events was higher in patients randomized to gabapentin than to women assigned to electroacupuncture, sham acupuncture, or placebo, Dr. Jun J. Mao reported at the San Antonio Breast Cancer Symposium.

The study included 120 women who had completed their primary treatment for breast cancer and were experiencing troublesome hot flashes at least twice daily. Participants were randomized to 8 weeks of treatment with electroacupuncture, sham acupuncture, gabapentin at 300 mg t.i.d., or placebo. The primary endpoint was change from baseline to week 8 in patients’ hot flash composite score as gleaned from their daily hot flash diary. The secondary endpoint was durability of response based upon the hot flash composite score at week 24, fully 4 months after patients went off treatment, explained Dr. Mao, a family physician and licensed acupuncturist at the University of Pennsylvania, Philadelphia.

From a baseline mean hot flash score of 14.3, scores dropped by a mean of 7.4 points by week 8 in the electroacupuncture recipients. This represented a significantly greater treatment effect, compared with the reductions of 5.9 points with sham acupuncture, 5.2 points with gabapentin, and 3.4 points with placebo.

Only acupuncture showed a durable treatment benefit at 24 weeks. Indeed, the magnitude of the reduction in hot flash scores 4 months after the final acupuncture session was, intriguingly, even greater than at 8 weeks, both for electroacupuncture and sham acupuncture. The mean reduction in hot flash score at 24 weeks was 8.5 points in the electroacupuncture group, as compared with 7.4 points at week 8. Sham acupuncture showed a mean 6.1-point decrease in the hot flash score at week 24, gabapentin a 4.6-point reduction, and placebo a 2.8-point drop.

No serious adverse events were noted during the study. However, 48% of gabapentin-treated patients reported treatment-related adverse events, compared with 29% on placebo, 19% who got electroacupuncture, and 3% with sham acupuncture, Dr. Mao continued.

The adherence rate to acupuncture was 90%, versus 75% with gabapentin.

Electroacupuncture entailed using a TENS unit to pass a 2-Hz current through acupuncture needles placed at traditional points. There were two sessions per week for the first 2 weeks, then once-weekly sessions for the remaining 6 weeks.

“The needle insertion is generally brief, 5-10 minutes. Then the patient rests for about 20 minutes,” according to the family physician.

Sham acupuncture utilized nonpenetrating Streitberger needles at nontraditional acupuncture points.

Discussant Dr. Michelle E. Melisko noted that this is one of the largest randomized trials of acupuncture for hot flashes ever done, and it included women of widely varied ages and a substantial African American population. It’s also the first study she’s aware of to compare acupuncture to a nonhormonal medication.

She observed that hot flashes tend to be particularly frequent, severe, and often more debilitating in breast cancer survivors than in the general population. Gabapentin (Neurontin) and venlafaxine (Effexor) are probably the two most widely prescribed centrally acting drugs for treatment of hot flashes in breast cancer survivors.

“Gabapentin is often an appealing choice. In my practice it’s a drug often used to kill two birds with one stone. It can make people sleepy, so if patients are having hot flashes and night sweats it’s nice to give them an agent they can take at bedtime that might have the dual effects of reducing hot flashes as well as improving their sleep,” said Dr. Melisko, an oncologist at the University of California, San Francisco.

She noted that a systematic review of gabapentin for hot flashes in 901 patients in seven clinical trials, including four studies in breast cancer survivors, concluded the drug resulted in 20%-30% reductions in hot flash frequency and severity, but with a dropout rate twice that for placebo (Clin. Therapeutics 2009;31:221-35).But lots of breast cancer survivors say they don’t want to take an additional side effect–laden medication to treat a different set of treatment-induced side effects, Dr. Melisko continued. They’re interested in trying complementary and alternative medicine. And while a Cochrane review has concluded that acupuncture resulted in a significant reduction in hot flash severity but not frequency (Cochrane Database Syst. Rev. 2013 July 30;7:CD007410), Dr. Melisko noted that many of the trials included in that analysis may have been too brief to give acupuncture a fair shake.

Dr. Mao agreed.

“By 4 weeks in our trial you see only about one-half of the eventual effect of electroacupuncture. So if you design a short trial you may not get to the full therapeutic dose,” he said. “With acupuncture, it’s a slow start but eventual substantial effect. I tell patients you need to give acupuncture a therapeutic trial of at least six treatments. If at that point you don’t have any benefit, it may not work for you, but if you don’t try that amount it’s suboptimal.”

In acupuncture trials across the board, whether in the setting of cancer, chronic pain, or various other conditions, roughly one-third of patients are nonresponders, according to Dr. Mao.

His study was funded by the NIH’s National Center for Complementary and Alternative Medicine. He reported having no financial conflicts.

bjancin@frontlinemedcom.com