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Decreased weight, increased activity improved breast cancer survival for some women
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.
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.
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.
On Twitter @alz_gal
AT SABCS 2014
Key clinical point: Diet and exercise seem to improve outcomes in some women with breast cancer.
Major finding: A dietary intervention conferred an average 2-year survival advantage upon women with ER+/PR+ breast cancer.
Data source: The randomized trial comprised 2,437 women with early-stage, treated breast cancer.
Disclosures: The National Cancer Institute sponsored the trial. Dr. Chlebowski had no financial disclosures.
VIDEO: SABCS 2014 roundtable with Dr. William J. Gradishar and Dr. Hope S. Rugo
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.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
EXPERT ANALYSIS FROM SABCS 2014
Fulvestrant bests anastrozole in advanced breast cancer
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.
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.
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.
AT SABCS 2014
Key clinical point: The selective estrogen receptor down-regulator fulvestrant proved superior to anastrozole in disease progression and overall survival in women with hormone receptor–positive advanced breast cancer.
Major finding: At a median follow-up of 48.8 months, overall survival was 54.1 months in patients on fulvestrant, fully 5.7 months more than the 48.4 months with anastrozole.
Data source: The FIRST trial was a phase II, open-label study of 205 women randomized to fulvestrant or anastrozole.
Disclosures: The FIRST trial was sponsored by AstraZeneca. The presenter has received research funds from and served as a consultant to the company.
Predictors of resolution in navigated patients with abnormal cancer screening tests
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
Click on the PDF icon at the top of this introduction to read the full article.
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
Click on the PDF icon at the top of this introduction to read the full article.
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
Click on the PDF icon at the top of this introduction to read the full article.
Information and communication needs of Chinese American breast cancer patients: perspectives on survivorship care planning
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.
Click on the PDF icon at the top of this introduction to read the full article.
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.
Click on the PDF icon at the top of this introduction to read the full article.
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.
Click on the PDF icon at the top of this introduction to read the full article.
Genetic test predicts 10-year risk of DCIS recurrence
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.
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.
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.
On Twitter @alz_gal
AT SABCS 2014
Key clinical point: A genetic assay can accurately predict the 10-year risk of local recurrence in women with ductal carcinoma in situ.
Major finding: Women with the highest risk as graded by Oncotype DCIS Score were 68% more likely to develop recurrence than were those in the lowest risk group.
Data source: The retrospective validation study comprised 257 women with DCIS who were treated with breast-conserving surgery alone.
Disclosures:Funding was provided by the Canadian Cancer Society Research Institute and a research grant from Genomic Health, which makes the test. Dr. Rakovitch had no conflicts of interest.
Acupuncture beats gabapentin for hot flashes in RCT
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.
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.
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.
AT SABCS 2014
Key clinical point: Breast cancer survivors with frequent hot flashes obtained more benefit from 8 weeks of electroacupuncture than gabapentin.
Major finding: Mean hot flash composite scores after 8 weeks of electroacupuncture fell by 7.4 points from baseline, compared with a 5.2-point drop with gabapentin at 900 mg/day.
Data source: This was a randomized, prospective trial including 120 breast cancer survivors with troublesome hot flashes at least twice daily.
Disclosures: The study was funded by the National Center for Complementary and Alternative Medicine. The presenter reported having no financial conflicts.
AI-induced symptoms don’t predict survival
Vasomotor and musculoskeletal symptoms associated with aromatase inhibitor adjuvant therapy do not signal a more intense treatment response and thus do not predict better survival in women with breast cancer, according to a report published online Dec. 15 in Journal of Clinical Oncology.
Even though several retrospective exploratory analyses have suggested that treatment-emergent symptoms may be associated with improved survival in this patient population, this secondary analysis of data in a large international prospective randomized clinical trial argues otherwise. “It is premature to counsel patients on whether to continue or change their adjuvant AI therapy based on symptoms,” said Dr. Vered Stearns of the Kimmel Cancer Center, Johns Hopkins University, Baltimore, and her associates.
To investigate whether adverse effects might be useful in informing treatment decisions, the investigators analyzed data from the NCIC Clinical Trials Group MA.27 trial – an open-label phase III study conducted in 2003-2008 and involving 7,567 postmenopausal women who had hormone receptor–positive breast cancer. After completing their initial treatment and a washout period to allow for any adverse effects related to it, these participants were randomly assigned to receive adjuvant therapy with either anastrozole (3,787 women) or exemestane (3,789 women) and followed for a median of 4 years. To collect treatment-related symptoms in a standardized manner, they completed Common Terminology Criteria for Adverse Events questionnaires at baseline and at regular intervals afterward.
A relatively high number of these participants (34%) reported already having such symptoms at baseline, which may reflect rebound symptoms from hormone therapy withdrawal during the washout period. For women who had no symptoms at baseline, 25% reported them at 6 months and 52% reported them by 12 months.
At 3-month follow-up, 96 of the 403 women with severe symptoms discontinued treatment; the rate of treatment discontinuation was 12% at 6 months and 10% at 12 months. The most common reason cited for discontinuation was joint pain.
The emergence of new or worsening vasomotor and musculoskeletal symptoms showed no association with recurrence-free survival. There was no correlation between recurrence-free survival and symptoms at baseline or symptoms induced by AI therapy at 3 months, 6 months, or 12 months in the overall study population or in any subgroup of patients, Dr. Stearns and her associates said (J. Clin. Oncol. 2014 Dec. 15 [doi:10.1200;JCO.2014.57.6926]).
These findings indicate that treatment-emergent symptoms should be managed as effectively as possible but not held up as evidence that adjuvant therapy is working. “Women should be supported through treatment and encouraged to remain on their AI regardless of their symptoms,” the investigators added.
The notion that toxicity related to treatment can be a surrogate for treatment efficacy has long been embedded in the psyche of patients. Oncologists also can mistakenly believe that with cancer, which warrants the most aggressive possible therapy, the strength of a treatment is reflected in the adverse effects it produces.
 |
Dr. William J. Gradishar |
But toxicity must not be considered an automatic surrogate measure of clinical benefit. Much of cancer treatments’ toxicity results from collateral damage: nontargeted effects to normal tissue that may or may not share features of the target cancer cell.
Dr. William J. Gradishar is at Northwestern University, Chicago. His financial disclosures are available at www.jco.org. Dr. Gradishar made these remarks in an editorial accompanying Dr. Stearns’s report (J. Clin. Oncol. 2014 Dec. 15 [doi:10.1200/JCO.2014.59.0919]).
The notion that toxicity related to treatment can be a surrogate for treatment efficacy has long been embedded in the psyche of patients. Oncologists also can mistakenly believe that with cancer, which warrants the most aggressive possible therapy, the strength of a treatment is reflected in the adverse effects it produces.
|
Dr. William J. Gradishar |
But toxicity must not be considered an automatic surrogate measure of clinical benefit. Much of cancer treatments’ toxicity results from collateral damage: nontargeted effects to normal tissue that may or may not share features of the target cancer cell.
Dr. William J. Gradishar is at Northwestern University, Chicago. His financial disclosures are available at www.jco.org. Dr. Gradishar made these remarks in an editorial accompanying Dr. Stearns’s report (J. Clin. Oncol. 2014 Dec. 15 [doi:10.1200/JCO.2014.59.0919]).
The notion that toxicity related to treatment can be a surrogate for treatment efficacy has long been embedded in the psyche of patients. Oncologists also can mistakenly believe that with cancer, which warrants the most aggressive possible therapy, the strength of a treatment is reflected in the adverse effects it produces.
|
Dr. William J. Gradishar |
But toxicity must not be considered an automatic surrogate measure of clinical benefit. Much of cancer treatments’ toxicity results from collateral damage: nontargeted effects to normal tissue that may or may not share features of the target cancer cell.
Dr. William J. Gradishar is at Northwestern University, Chicago. His financial disclosures are available at www.jco.org. Dr. Gradishar made these remarks in an editorial accompanying Dr. Stearns’s report (J. Clin. Oncol. 2014 Dec. 15 [doi:10.1200/JCO.2014.59.0919]).
Vasomotor and musculoskeletal symptoms associated with aromatase inhibitor adjuvant therapy do not signal a more intense treatment response and thus do not predict better survival in women with breast cancer, according to a report published online Dec. 15 in Journal of Clinical Oncology.
Even though several retrospective exploratory analyses have suggested that treatment-emergent symptoms may be associated with improved survival in this patient population, this secondary analysis of data in a large international prospective randomized clinical trial argues otherwise. “It is premature to counsel patients on whether to continue or change their adjuvant AI therapy based on symptoms,” said Dr. Vered Stearns of the Kimmel Cancer Center, Johns Hopkins University, Baltimore, and her associates.
To investigate whether adverse effects might be useful in informing treatment decisions, the investigators analyzed data from the NCIC Clinical Trials Group MA.27 trial – an open-label phase III study conducted in 2003-2008 and involving 7,567 postmenopausal women who had hormone receptor–positive breast cancer. After completing their initial treatment and a washout period to allow for any adverse effects related to it, these participants were randomly assigned to receive adjuvant therapy with either anastrozole (3,787 women) or exemestane (3,789 women) and followed for a median of 4 years. To collect treatment-related symptoms in a standardized manner, they completed Common Terminology Criteria for Adverse Events questionnaires at baseline and at regular intervals afterward.
A relatively high number of these participants (34%) reported already having such symptoms at baseline, which may reflect rebound symptoms from hormone therapy withdrawal during the washout period. For women who had no symptoms at baseline, 25% reported them at 6 months and 52% reported them by 12 months.
At 3-month follow-up, 96 of the 403 women with severe symptoms discontinued treatment; the rate of treatment discontinuation was 12% at 6 months and 10% at 12 months. The most common reason cited for discontinuation was joint pain.
The emergence of new or worsening vasomotor and musculoskeletal symptoms showed no association with recurrence-free survival. There was no correlation between recurrence-free survival and symptoms at baseline or symptoms induced by AI therapy at 3 months, 6 months, or 12 months in the overall study population or in any subgroup of patients, Dr. Stearns and her associates said (J. Clin. Oncol. 2014 Dec. 15 [doi:10.1200;JCO.2014.57.6926]).
These findings indicate that treatment-emergent symptoms should be managed as effectively as possible but not held up as evidence that adjuvant therapy is working. “Women should be supported through treatment and encouraged to remain on their AI regardless of their symptoms,” the investigators added.
Vasomotor and musculoskeletal symptoms associated with aromatase inhibitor adjuvant therapy do not signal a more intense treatment response and thus do not predict better survival in women with breast cancer, according to a report published online Dec. 15 in Journal of Clinical Oncology.
Even though several retrospective exploratory analyses have suggested that treatment-emergent symptoms may be associated with improved survival in this patient population, this secondary analysis of data in a large international prospective randomized clinical trial argues otherwise. “It is premature to counsel patients on whether to continue or change their adjuvant AI therapy based on symptoms,” said Dr. Vered Stearns of the Kimmel Cancer Center, Johns Hopkins University, Baltimore, and her associates.
To investigate whether adverse effects might be useful in informing treatment decisions, the investigators analyzed data from the NCIC Clinical Trials Group MA.27 trial – an open-label phase III study conducted in 2003-2008 and involving 7,567 postmenopausal women who had hormone receptor–positive breast cancer. After completing their initial treatment and a washout period to allow for any adverse effects related to it, these participants were randomly assigned to receive adjuvant therapy with either anastrozole (3,787 women) or exemestane (3,789 women) and followed for a median of 4 years. To collect treatment-related symptoms in a standardized manner, they completed Common Terminology Criteria for Adverse Events questionnaires at baseline and at regular intervals afterward.
A relatively high number of these participants (34%) reported already having such symptoms at baseline, which may reflect rebound symptoms from hormone therapy withdrawal during the washout period. For women who had no symptoms at baseline, 25% reported them at 6 months and 52% reported them by 12 months.
At 3-month follow-up, 96 of the 403 women with severe symptoms discontinued treatment; the rate of treatment discontinuation was 12% at 6 months and 10% at 12 months. The most common reason cited for discontinuation was joint pain.
The emergence of new or worsening vasomotor and musculoskeletal symptoms showed no association with recurrence-free survival. There was no correlation between recurrence-free survival and symptoms at baseline or symptoms induced by AI therapy at 3 months, 6 months, or 12 months in the overall study population or in any subgroup of patients, Dr. Stearns and her associates said (J. Clin. Oncol. 2014 Dec. 15 [doi:10.1200;JCO.2014.57.6926]).
These findings indicate that treatment-emergent symptoms should be managed as effectively as possible but not held up as evidence that adjuvant therapy is working. “Women should be supported through treatment and encouraged to remain on their AI regardless of their symptoms,” the investigators added.
Key clinical point: Vasomotor and musculoskeletal symptoms induced by aromatase inhibitors do not signal a more-intense treatment response or improved survival in breast cancer.
Major finding:There was no correlation between recurrence-free survival and symptoms at baseline or symptoms induced by AI therapy at 3 months, 6 months, or 12 months in the overall study population or in any subgroup of patients.
Data source: A secondary analysis of data in a large international randomized phase III clinical trial involving 7,576 postmenopausal women with hormone receptor–positive breast cancer who were followed for a median of 4 years.
Disclosures: This study was supported by the NCIC Clinical Trials Group, Canada; the Canadian Cancer Society Research Institute; the U.S. National Cancer Institute; the International Breast Cancer Study Group; Pfizer; the Susan G. Komen for the Cure; and the Avon Foundation, New York. Dr. Stearns reported receiving research funding from AbbVie, Celgene, Merck, Novartis, Pfizer, MedImmune, and Puma, and her associates reported ties to numerous industry sources.
VIDEO: What have we learned about prevention of breast cancer from IBIS-1?
SAN ANTONIO – An analysis from 2 decades of follow-up in women who took tamoxifen or placebo for breast cancer prevention showed the benefit in prevention persists, but no benefit in survival has yet to emerge.
Dr. Erica Mayer of the Dana-Farber Cancer Institute, Boston, discusses IBIS-1 results in an interview and details what those results will mean in the clinic, at the San Antonio Breast Cancer Symposium.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @alz_gal
SAN ANTONIO – An analysis from 2 decades of follow-up in women who took tamoxifen or placebo for breast cancer prevention showed the benefit in prevention persists, but no benefit in survival has yet to emerge.
Dr. Erica Mayer of the Dana-Farber Cancer Institute, Boston, discusses IBIS-1 results in an interview and details what those results will mean in the clinic, at the San Antonio Breast Cancer Symposium.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @alz_gal
SAN ANTONIO – An analysis from 2 decades of follow-up in women who took tamoxifen or placebo for breast cancer prevention showed the benefit in prevention persists, but no benefit in survival has yet to emerge.
Dr. Erica Mayer of the Dana-Farber Cancer Institute, Boston, discusses IBIS-1 results in an interview and details what those results will mean in the clinic, at the San Antonio Breast Cancer Symposium.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @alz_gal
AT SABCS 2014
20 years after initiating preventive tamoxifen, less breast cancer but no survival benefit
SAN ANTONIO – Five years of tamoxifen provided 20 years of breast cancer prevention to some at-risk women who took it prophylactically.
However, their 20-year all-cause mortality was no different from those taking placebo (182 vs. 166 deaths), nor was their mortality from breast cancer (31 vs. 26, respectively), Jack Cuzick, Ph.D., said at the San Antonio Breast Cancer Symposium.
“While we saw clear, lasting benefits of tamoxifen in reducing breast cancer incidence, uncertainty with respect to mortality remains,” said Dr. Cuzick, the John Snow professor of epidemiology at Wolfson Institute of Preventive Medicine at Queen Mary University, London.
He suggested that, in light of the small number of deaths, the study was not sufficiently powered to detect any significant survival difference. But women in the IBIS-1 trial will continue to be observed, and future analyses could clarify the issue, he added.
“Although 20 years seems like a long follow-up time, it is actually too early to make any clear statement about mortality,” he said. “However, we are concerned about an excess emergence of ER-negative tumors, which we saw after 10 years.”
The study was simultaneously published on Dec. 13 in Lancet Oncology
IBIS-1 randomized 7,154 healthy pre- and postmenopausal women to 5 years of either 20 mg daily tamoxifen or placebo. These women were aged 35-70 years at baseline and presented with an increased breast cancer risk attributable to a family history.
IBIS-1 was first reported in 2002, when 4-year follow-up found a 32% reduction in breast cancer risk associated with tamoxifen. But it also found a significant increase in deaths among that group (25 vs.11 in placebo), many of which were attributable to more endometrial cancer (11 vs. 5).
In 2007, the investigators published the trial’s 8-10 year findings. At that time, tamoxifen was associated with a 27% decreased risk of any breast cancer, and a 34% decreased risk of developing an ER-positive cancer. It found a consistent prophylactic benefit for tamoxifen; most of the risk reduction, however, occurred in the 5-year active treatment phase.
The significant increase in death had continued (25 vs. 11), although that report indicated that no specific cause, including endometrial cancer, drove that finding.
At the meeting, Dr. Cuzick discussed the latest findings of IBIS-1, which has now followed the cohort for up to 20 years (median, 16 years).
“We have seen a continued separation of the cancer incidence curves, with a 20-year incidence of 7.8% vs. 12.3%,” Dr. Cuzick said. “We saw that the 30% overall reduction was maintained; the number needed to treat to prevent one breast cancer was 22, which is very favorable when compared to prevention strategies for other diseases.”
The incidence of ER-positive tumors was reduced, compared with placebo, he added (4.9% vs. 8.3%), with a number needed to treat of 29. However, Dr. Cuzick said, there was a slight increase in the incidence of ER-negative tumors after 10 years.
“This is likely because these are tumors that would have appeared earlier as ER-positive tumors, but under tamoxifen, they were held back for some time and eventually broke out as ER-negative tumors.”
Hormone therapy was allowed in IBIS-1, and about 50% of women were taking hormones during at least part of the study. They did not experience the same level of benefit form tamoxifen as those who were not taking hormone therapy (12% vs. 38%). “This is very clear evidence that the benefits are substantially greater in those who are not using concurrent [hormone therapy] when on tamoxifen,” he said.
However, tamoxifen was associated with side effects and risks, including an increased risk of developing other cancers. Most concerning was the 45% increase in the risk of endometrial cancer, which accounted for five deaths in the treatment group; there were no deaths from endometrial cancer in the placebo group.
“We had hoped that endometrial cancer might not translate into such a large morality increase as there were no deaths due to this in the 8-year follow-up. We do need to be aware of this.”
Recurrent breast cancer was the single largest cause of death, but the between-group difference was not significant (26 vs. 31). Cardiovascular deaths were similar between the groups, and all that did occur, did so during the treatment period.
Nonmelanoma skin cancers were 39% more likely in the tamoxifen group, although they caused no deaths. “This was a very large increase and a surprise; we really don’t understand it,” Dr. Cuzick said.
There were 12 fewer colorectal cancers in the tamoxifen group. “That there was a slight reduction here is of some interest, as we did not see at all with placebo.”
The tamoxifen-associated risk of any other cancers was nonsignificant.
The IBIS-I trial was supported by Cancer Research UK. Dr. Cuzick has received funding for other trials from AstraZeneca and is a consultant for AstraZeneca. The company also provided both the study drug and placebo.
On Twitter @alz_gal
SAN ANTONIO – Five years of tamoxifen provided 20 years of breast cancer prevention to some at-risk women who took it prophylactically.
However, their 20-year all-cause mortality was no different from those taking placebo (182 vs. 166 deaths), nor was their mortality from breast cancer (31 vs. 26, respectively), Jack Cuzick, Ph.D., said at the San Antonio Breast Cancer Symposium.
“While we saw clear, lasting benefits of tamoxifen in reducing breast cancer incidence, uncertainty with respect to mortality remains,” said Dr. Cuzick, the John Snow professor of epidemiology at Wolfson Institute of Preventive Medicine at Queen Mary University, London.
He suggested that, in light of the small number of deaths, the study was not sufficiently powered to detect any significant survival difference. But women in the IBIS-1 trial will continue to be observed, and future analyses could clarify the issue, he added.
“Although 20 years seems like a long follow-up time, it is actually too early to make any clear statement about mortality,” he said. “However, we are concerned about an excess emergence of ER-negative tumors, which we saw after 10 years.”
The study was simultaneously published on Dec. 13 in Lancet Oncology
IBIS-1 randomized 7,154 healthy pre- and postmenopausal women to 5 years of either 20 mg daily tamoxifen or placebo. These women were aged 35-70 years at baseline and presented with an increased breast cancer risk attributable to a family history.
IBIS-1 was first reported in 2002, when 4-year follow-up found a 32% reduction in breast cancer risk associated with tamoxifen. But it also found a significant increase in deaths among that group (25 vs.11 in placebo), many of which were attributable to more endometrial cancer (11 vs. 5).
In 2007, the investigators published the trial’s 8-10 year findings. At that time, tamoxifen was associated with a 27% decreased risk of any breast cancer, and a 34% decreased risk of developing an ER-positive cancer. It found a consistent prophylactic benefit for tamoxifen; most of the risk reduction, however, occurred in the 5-year active treatment phase.
The significant increase in death had continued (25 vs. 11), although that report indicated that no specific cause, including endometrial cancer, drove that finding.
At the meeting, Dr. Cuzick discussed the latest findings of IBIS-1, which has now followed the cohort for up to 20 years (median, 16 years).
“We have seen a continued separation of the cancer incidence curves, with a 20-year incidence of 7.8% vs. 12.3%,” Dr. Cuzick said. “We saw that the 30% overall reduction was maintained; the number needed to treat to prevent one breast cancer was 22, which is very favorable when compared to prevention strategies for other diseases.”
The incidence of ER-positive tumors was reduced, compared with placebo, he added (4.9% vs. 8.3%), with a number needed to treat of 29. However, Dr. Cuzick said, there was a slight increase in the incidence of ER-negative tumors after 10 years.
“This is likely because these are tumors that would have appeared earlier as ER-positive tumors, but under tamoxifen, they were held back for some time and eventually broke out as ER-negative tumors.”
Hormone therapy was allowed in IBIS-1, and about 50% of women were taking hormones during at least part of the study. They did not experience the same level of benefit form tamoxifen as those who were not taking hormone therapy (12% vs. 38%). “This is very clear evidence that the benefits are substantially greater in those who are not using concurrent [hormone therapy] when on tamoxifen,” he said.
However, tamoxifen was associated with side effects and risks, including an increased risk of developing other cancers. Most concerning was the 45% increase in the risk of endometrial cancer, which accounted for five deaths in the treatment group; there were no deaths from endometrial cancer in the placebo group.
“We had hoped that endometrial cancer might not translate into such a large morality increase as there were no deaths due to this in the 8-year follow-up. We do need to be aware of this.”
Recurrent breast cancer was the single largest cause of death, but the between-group difference was not significant (26 vs. 31). Cardiovascular deaths were similar between the groups, and all that did occur, did so during the treatment period.
Nonmelanoma skin cancers were 39% more likely in the tamoxifen group, although they caused no deaths. “This was a very large increase and a surprise; we really don’t understand it,” Dr. Cuzick said.
There were 12 fewer colorectal cancers in the tamoxifen group. “That there was a slight reduction here is of some interest, as we did not see at all with placebo.”
The tamoxifen-associated risk of any other cancers was nonsignificant.
The IBIS-I trial was supported by Cancer Research UK. Dr. Cuzick has received funding for other trials from AstraZeneca and is a consultant for AstraZeneca. The company also provided both the study drug and placebo.
On Twitter @alz_gal
SAN ANTONIO – Five years of tamoxifen provided 20 years of breast cancer prevention to some at-risk women who took it prophylactically.
However, their 20-year all-cause mortality was no different from those taking placebo (182 vs. 166 deaths), nor was their mortality from breast cancer (31 vs. 26, respectively), Jack Cuzick, Ph.D., said at the San Antonio Breast Cancer Symposium.
“While we saw clear, lasting benefits of tamoxifen in reducing breast cancer incidence, uncertainty with respect to mortality remains,” said Dr. Cuzick, the John Snow professor of epidemiology at Wolfson Institute of Preventive Medicine at Queen Mary University, London.
He suggested that, in light of the small number of deaths, the study was not sufficiently powered to detect any significant survival difference. But women in the IBIS-1 trial will continue to be observed, and future analyses could clarify the issue, he added.
“Although 20 years seems like a long follow-up time, it is actually too early to make any clear statement about mortality,” he said. “However, we are concerned about an excess emergence of ER-negative tumors, which we saw after 10 years.”
The study was simultaneously published on Dec. 13 in Lancet Oncology
IBIS-1 randomized 7,154 healthy pre- and postmenopausal women to 5 years of either 20 mg daily tamoxifen or placebo. These women were aged 35-70 years at baseline and presented with an increased breast cancer risk attributable to a family history.
IBIS-1 was first reported in 2002, when 4-year follow-up found a 32% reduction in breast cancer risk associated with tamoxifen. But it also found a significant increase in deaths among that group (25 vs.11 in placebo), many of which were attributable to more endometrial cancer (11 vs. 5).
In 2007, the investigators published the trial’s 8-10 year findings. At that time, tamoxifen was associated with a 27% decreased risk of any breast cancer, and a 34% decreased risk of developing an ER-positive cancer. It found a consistent prophylactic benefit for tamoxifen; most of the risk reduction, however, occurred in the 5-year active treatment phase.
The significant increase in death had continued (25 vs. 11), although that report indicated that no specific cause, including endometrial cancer, drove that finding.
At the meeting, Dr. Cuzick discussed the latest findings of IBIS-1, which has now followed the cohort for up to 20 years (median, 16 years).
“We have seen a continued separation of the cancer incidence curves, with a 20-year incidence of 7.8% vs. 12.3%,” Dr. Cuzick said. “We saw that the 30% overall reduction was maintained; the number needed to treat to prevent one breast cancer was 22, which is very favorable when compared to prevention strategies for other diseases.”
The incidence of ER-positive tumors was reduced, compared with placebo, he added (4.9% vs. 8.3%), with a number needed to treat of 29. However, Dr. Cuzick said, there was a slight increase in the incidence of ER-negative tumors after 10 years.
“This is likely because these are tumors that would have appeared earlier as ER-positive tumors, but under tamoxifen, they were held back for some time and eventually broke out as ER-negative tumors.”
Hormone therapy was allowed in IBIS-1, and about 50% of women were taking hormones during at least part of the study. They did not experience the same level of benefit form tamoxifen as those who were not taking hormone therapy (12% vs. 38%). “This is very clear evidence that the benefits are substantially greater in those who are not using concurrent [hormone therapy] when on tamoxifen,” he said.
However, tamoxifen was associated with side effects and risks, including an increased risk of developing other cancers. Most concerning was the 45% increase in the risk of endometrial cancer, which accounted for five deaths in the treatment group; there were no deaths from endometrial cancer in the placebo group.
“We had hoped that endometrial cancer might not translate into such a large morality increase as there were no deaths due to this in the 8-year follow-up. We do need to be aware of this.”
Recurrent breast cancer was the single largest cause of death, but the between-group difference was not significant (26 vs. 31). Cardiovascular deaths were similar between the groups, and all that did occur, did so during the treatment period.
Nonmelanoma skin cancers were 39% more likely in the tamoxifen group, although they caused no deaths. “This was a very large increase and a surprise; we really don’t understand it,” Dr. Cuzick said.
There were 12 fewer colorectal cancers in the tamoxifen group. “That there was a slight reduction here is of some interest, as we did not see at all with placebo.”
The tamoxifen-associated risk of any other cancers was nonsignificant.
The IBIS-I trial was supported by Cancer Research UK. Dr. Cuzick has received funding for other trials from AstraZeneca and is a consultant for AstraZeneca. The company also provided both the study drug and placebo.
On Twitter @alz_gal
AT SABCS 2014
Key clinical point: Prophylactic tamoxifen reduced breast cancers in vulnerable women, compared with placebo, but didn’t affect overall mortality.
Major finding: Five years of tamoxifen treatment translated into a 30% decrease in the incidence of breast cancers among at-risk women, but there was no survival benefit at 20 years of follow-up.
Data source: The IBIS-1 trial randomized more than 7,000 women to 5 years of either tamoxifen or placebo.
Disclosures: The IBIS-I trial was supported by Cancer Research UK. Dr. Cuzick has received funding for other trials from AstraZeneca and is a consultant for AstraZeneca. The company also provided both the study drug and placebo.
