Breast Cancer

Radiation exposure is associated with an increased risk of secondary cancers. Knowing the approximate radiation exposure from diagnostic procedures in the first year after a breast cancer diagnosis could help educate patients and allow physicians to monitor them more closely for potential risks.

Click on the PDF icon at the top of this introduction to read the full article.

Radiation exposure is associated with an increased risk of secondary cancers. Knowing the approximate radiation exposure from diagnostic procedures in the first year after a breast cancer diagnosis could help educate patients and allow physicians to monitor them more closely for potential risks.

Click on the PDF icon at the top of this introduction to read the full article.

Radiation exposure is associated with an increased risk of secondary cancers. Knowing the approximate radiation exposure from diagnostic procedures in the first year after a breast cancer diagnosis could help educate patients and allow physicians to monitor them more closely for potential risks.

Click on the PDF icon at the top of this introduction to read the full article.

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

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

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

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

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

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

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

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

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

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

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

She reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

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

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

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

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

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

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

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

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

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

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

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

She reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

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

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

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

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

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

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

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

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

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

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

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

She reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

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

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

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

Bruce Jancin/Frontline Medical News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

bjancin@frontlinemedcom.com

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

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

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

Bruce Jancin/Frontline Medical News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

bjancin@frontlinemedcom.com

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

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

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

Bruce Jancin/Frontline Medical News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

bjancin@frontlinemedcom.com

SAN ANTONIO – Adjuvant aromatase inhibitor therapy in women with early-stage breast cancer was associated with worse oral health–related quality of life in a preliminary analysis from an ongoing prospective cohort study.

“Oral health is critical to overall health, and the findings of this study suggest the need to focus attention on dental health education for these patients related to improved home care regimens and optimizing intervals for dental evaluations,” Linda S. Taichman, Ph.D., said at the San Antonio Breast Cancer Symposium.

The study – the first ever to report on oral health issues in women with early breast cancer on aromatase inhibitors (AIs) – included 58 postmenopausal women. Half were on adjuvant AIs; the other half were recruited at the time of screening mammography, didn’t have breast cancer, and weren’t taking an AI. The two groups were similar in terms of demographics, frequency of daily brushing and flossing, and frequency of dental visits.

At entry into what is scheduled to be an 18-month study, participants completed the Oral Health Impact Profile–14 and the Michigan Oral Health–Related Quality of Life Scale, both of which measure self-reported dysfunction, discomfort, and disability on a self-rated 5-point scale.

The adjuvant AI users reported significantly lower oral health–related quality of life than controls in multiple domains: more pain and aching in the mouth; greater discomfort when eating; a need to limit the foods they eat; interruption of meals; a feeling of being self-conscious, tense, and embarrassed about problems in their mouth; and being irritable with others. The longer patients had been on an AI, the lower their oral health quality of life scores, Dr. Taichman of the University of Michigan School of Dentistry, Ann Arbor, reported.

Oral health quality of life was unrelated to whether a breast cancer patient had undergone chemotherapy.

Saliva flow rate as an indicator of oral health was measured at baseline. Women on AIs were less likely to be able to produce a 2-mL saliva sample.

The study sample size was insufficient to determine if there were differences between specific AIs in terms of patient oral health. Additional studies are ongoing, Dr. Taichman added.

She noted that both groups of women had room for improvement in terms of their oral care regimens. At baseline, only about 40% of subjects reported brushing every day, and less than half of the women flossed daily.

The study is funded by the Michigan Institute for Clinical Health Research. She reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

SAN ANTONIO – Adjuvant aromatase inhibitor therapy in women with early-stage breast cancer was associated with worse oral health–related quality of life in a preliminary analysis from an ongoing prospective cohort study.

“Oral health is critical to overall health, and the findings of this study suggest the need to focus attention on dental health education for these patients related to improved home care regimens and optimizing intervals for dental evaluations,” Linda S. Taichman, Ph.D., said at the San Antonio Breast Cancer Symposium.

The study – the first ever to report on oral health issues in women with early breast cancer on aromatase inhibitors (AIs) – included 58 postmenopausal women. Half were on adjuvant AIs; the other half were recruited at the time of screening mammography, didn’t have breast cancer, and weren’t taking an AI. The two groups were similar in terms of demographics, frequency of daily brushing and flossing, and frequency of dental visits.

At entry into what is scheduled to be an 18-month study, participants completed the Oral Health Impact Profile–14 and the Michigan Oral Health–Related Quality of Life Scale, both of which measure self-reported dysfunction, discomfort, and disability on a self-rated 5-point scale.

The adjuvant AI users reported significantly lower oral health–related quality of life than controls in multiple domains: more pain and aching in the mouth; greater discomfort when eating; a need to limit the foods they eat; interruption of meals; a feeling of being self-conscious, tense, and embarrassed about problems in their mouth; and being irritable with others. The longer patients had been on an AI, the lower their oral health quality of life scores, Dr. Taichman of the University of Michigan School of Dentistry, Ann Arbor, reported.

Oral health quality of life was unrelated to whether a breast cancer patient had undergone chemotherapy.

Saliva flow rate as an indicator of oral health was measured at baseline. Women on AIs were less likely to be able to produce a 2-mL saliva sample.

The study sample size was insufficient to determine if there were differences between specific AIs in terms of patient oral health. Additional studies are ongoing, Dr. Taichman added.

She noted that both groups of women had room for improvement in terms of their oral care regimens. At baseline, only about 40% of subjects reported brushing every day, and less than half of the women flossed daily.

The study is funded by the Michigan Institute for Clinical Health Research. She reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

SAN ANTONIO – Adjuvant aromatase inhibitor therapy in women with early-stage breast cancer was associated with worse oral health–related quality of life in a preliminary analysis from an ongoing prospective cohort study.

“Oral health is critical to overall health, and the findings of this study suggest the need to focus attention on dental health education for these patients related to improved home care regimens and optimizing intervals for dental evaluations,” Linda S. Taichman, Ph.D., said at the San Antonio Breast Cancer Symposium.

The study – the first ever to report on oral health issues in women with early breast cancer on aromatase inhibitors (AIs) – included 58 postmenopausal women. Half were on adjuvant AIs; the other half were recruited at the time of screening mammography, didn’t have breast cancer, and weren’t taking an AI. The two groups were similar in terms of demographics, frequency of daily brushing and flossing, and frequency of dental visits.

At entry into what is scheduled to be an 18-month study, participants completed the Oral Health Impact Profile–14 and the Michigan Oral Health–Related Quality of Life Scale, both of which measure self-reported dysfunction, discomfort, and disability on a self-rated 5-point scale.

The adjuvant AI users reported significantly lower oral health–related quality of life than controls in multiple domains: more pain and aching in the mouth; greater discomfort when eating; a need to limit the foods they eat; interruption of meals; a feeling of being self-conscious, tense, and embarrassed about problems in their mouth; and being irritable with others. The longer patients had been on an AI, the lower their oral health quality of life scores, Dr. Taichman of the University of Michigan School of Dentistry, Ann Arbor, reported.

Oral health quality of life was unrelated to whether a breast cancer patient had undergone chemotherapy.

Saliva flow rate as an indicator of oral health was measured at baseline. Women on AIs were less likely to be able to produce a 2-mL saliva sample.

The study sample size was insufficient to determine if there were differences between specific AIs in terms of patient oral health. Additional studies are ongoing, Dr. Taichman added.

She noted that both groups of women had room for improvement in terms of their oral care regimens. At baseline, only about 40% of subjects reported brushing every day, and less than half of the women flossed daily.

The study is funded by the Michigan Institute for Clinical Health Research. She reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

SAN ANTONIO – Breast cancer mortality in American women under age 50 declined markedly among whites during a recent two-decade period, less so in blacks.

“The racial gaps in survival have not closed. Young black women continue to have a worse outcome than young whites,” Dr. Foluso O. Ademuyiwa said at the San Antonio Breast Cancer Symposium.

She presented an analysis of Surveillance, Epidemiology, and End Results (SEER) registry data that included 162,976 women diagnosed with invasive breast cancer at age 18-49 during 1990-2009. Whites accounted for 77.7% of the total, blacks 12.5%, and other races 9.8%.

Twenty percent of patients had died by the median followup of 85 months. Five- and 10-year overall survival rates were 87.9% and 79.5%, respectively, among white patients, 74.9% and 64.3% for blacks, and 88.5% and 80.7% for women of other races, reported Dr. Ademuyiwa of Washington University, St. Louis.

During all 5-year sections of the study period, the highest risk of breast cancer mortality was in the first 3 years following diagnosis. However, annual risk of mortality in the first 3 years declined for white women from 3.4% during 1990-1994 to 1.9% during 2005-2009, and from 6.4% during 1990-1994 to 4.5% during 2005-2009 for black women.

Young black breast cancer patients had a more aggressive tumor biology. Thirty-seven percent of them had estrogen receptor–negative tumors, compared with 24% of white patients. Their disease was also at a higher stage and grade at diagnosis. Moreover, their tumors were larger in size; only 34.5% of black patients’ tumors were less than 2 cm in size, compared with 47.3% for white patients and 45.3% for women of other races.

A greater proportion of the invasive breast cancer cases in young women were diagnosed in more recent years. Roughly 13% of all cases in the SEER registry for 1990-2009 were diagnosed in 1990-1994, 16% in 1995-1999, 35% in 2000-2004, and 36% during 2005-2009. The explanation for this trend may be more widespread use of screening, changes in the reproductive risk profile over time, or some combination of the two factors, according to Dr. Ademuyiwa.

She reported having no financial conflicts with regard to this study.

bjancin@frontlinemedcom.com

SAN ANTONIO – Breast cancer mortality in American women under age 50 declined markedly among whites during a recent two-decade period, less so in blacks.

“The racial gaps in survival have not closed. Young black women continue to have a worse outcome than young whites,” Dr. Foluso O. Ademuyiwa said at the San Antonio Breast Cancer Symposium.

She presented an analysis of Surveillance, Epidemiology, and End Results (SEER) registry data that included 162,976 women diagnosed with invasive breast cancer at age 18-49 during 1990-2009. Whites accounted for 77.7% of the total, blacks 12.5%, and other races 9.8%.

Twenty percent of patients had died by the median followup of 85 months. Five- and 10-year overall survival rates were 87.9% and 79.5%, respectively, among white patients, 74.9% and 64.3% for blacks, and 88.5% and 80.7% for women of other races, reported Dr. Ademuyiwa of Washington University, St. Louis.

During all 5-year sections of the study period, the highest risk of breast cancer mortality was in the first 3 years following diagnosis. However, annual risk of mortality in the first 3 years declined for white women from 3.4% during 1990-1994 to 1.9% during 2005-2009, and from 6.4% during 1990-1994 to 4.5% during 2005-2009 for black women.

Young black breast cancer patients had a more aggressive tumor biology. Thirty-seven percent of them had estrogen receptor–negative tumors, compared with 24% of white patients. Their disease was also at a higher stage and grade at diagnosis. Moreover, their tumors were larger in size; only 34.5% of black patients’ tumors were less than 2 cm in size, compared with 47.3% for white patients and 45.3% for women of other races.

A greater proportion of the invasive breast cancer cases in young women were diagnosed in more recent years. Roughly 13% of all cases in the SEER registry for 1990-2009 were diagnosed in 1990-1994, 16% in 1995-1999, 35% in 2000-2004, and 36% during 2005-2009. The explanation for this trend may be more widespread use of screening, changes in the reproductive risk profile over time, or some combination of the two factors, according to Dr. Ademuyiwa.

She reported having no financial conflicts with regard to this study.

bjancin@frontlinemedcom.com

SAN ANTONIO – Breast cancer mortality in American women under age 50 declined markedly among whites during a recent two-decade period, less so in blacks.

“The racial gaps in survival have not closed. Young black women continue to have a worse outcome than young whites,” Dr. Foluso O. Ademuyiwa said at the San Antonio Breast Cancer Symposium.

She presented an analysis of Surveillance, Epidemiology, and End Results (SEER) registry data that included 162,976 women diagnosed with invasive breast cancer at age 18-49 during 1990-2009. Whites accounted for 77.7% of the total, blacks 12.5%, and other races 9.8%.

Twenty percent of patients had died by the median followup of 85 months. Five- and 10-year overall survival rates were 87.9% and 79.5%, respectively, among white patients, 74.9% and 64.3% for blacks, and 88.5% and 80.7% for women of other races, reported Dr. Ademuyiwa of Washington University, St. Louis.

During all 5-year sections of the study period, the highest risk of breast cancer mortality was in the first 3 years following diagnosis. However, annual risk of mortality in the first 3 years declined for white women from 3.4% during 1990-1994 to 1.9% during 2005-2009, and from 6.4% during 1990-1994 to 4.5% during 2005-2009 for black women.

Young black breast cancer patients had a more aggressive tumor biology. Thirty-seven percent of them had estrogen receptor–negative tumors, compared with 24% of white patients. Their disease was also at a higher stage and grade at diagnosis. Moreover, their tumors were larger in size; only 34.5% of black patients’ tumors were less than 2 cm in size, compared with 47.3% for white patients and 45.3% for women of other races.

A greater proportion of the invasive breast cancer cases in young women were diagnosed in more recent years. Roughly 13% of all cases in the SEER registry for 1990-2009 were diagnosed in 1990-1994, 16% in 1995-1999, 35% in 2000-2004, and 36% during 2005-2009. The explanation for this trend may be more widespread use of screening, changes in the reproductive risk profile over time, or some combination of the two factors, according to Dr. Ademuyiwa.

She reported having no financial conflicts with regard to this study.

bjancin@frontlinemedcom.com

Adjuvant therapy with trastuzumab plus paclitaxel yielded a 3-year recurrence rate of < 2% in an uncontrolled, nonrandomized study involving women who had small stage I HER2-positive breast cancers, according to a report published online Jan. 8 in the New England Journal of Medicine.

Currently no standard treatment is recommended for such patients, and clinicians must weigh the generally favorable outcomes for small, stage I tumors that aren’t targeted with adjuvant chemotherapy against the potential for considerable toxic effects from adjuvant chemotherapy. Clinical trials of trastuzumab have focused on patients with more advanced cancers. “Although patients with stage I HER2-positive tumors are expected to derive a smaller absolute benefit from adjuvant therapy than those with larger or node-positive tumors, they remain at more than minimal risk for a recurrence of breast cancer,” said Dr. Sara M. Tolaney of the department of medical oncology, Dana-Farber Cancer Institute, Boston, and her associates.

Their industry-sponsored single-group study involved 406 patients with a median age of 55 years (range, 24-85 years) whose breast adenocarcinomas measured no more than 3 cm. After undergoing surgical excisions, all the study participants were assigned to receive weekly IV paclitaxel and IV trastuzumab for 12 weeks, after which trastuzumab could be continued at the same weekly dose for 40 weeks or the regimen could be changed to a slightly higher dose every 3 weeks for 40 weeks.

A total of 356 patients (87.7%) completed the full year of adjuvant trastuzumab. Women who opted for partial- or whole-breast irradiation commenced that treatment after completing paclitaxel and while taking trastuzumab, and those who chose hormonal therapy also began taking those agents after completing paclitaxel and while taking trastuzumab. Median follow-up was 4 years (maximum, 6.2 years).

At 3-year follow-up, the rate of cancer-free survival was 98.7%, which was higher than would have been predicted by historical data; there were four distant and four local or regional metastases. According to the study’s statistical design, adjuvant trastuzumab would be considered successful if the 3-year recurrence rate were 5% or lower and there were 39 or fewer metastases, Dr. Tolaney and her associates said (N. Engl. J. Med. 2015 Jan. 8 [doi:10.1056/NEJM0a1406281]).

A total of 6% of patients withdrew from the study because of treatment-related adverse effects. The most important known adverse effect of trastuzumab is left ventricular dysfunction, so cardiac function was assessed at several intervals during the year of active therapy. Two patients (0.5%) developed grade 3 LV dysfunction during treatment, and both recovered after the drug was discontinued. Thirteen patients (3.2%) showed an asymptomatic decline in ejection fraction that led to an interruption in trastuzumab therapy; this normalized in 11 of them, who then resumed the treatment. Seven patients developed grade 3 or 4 allergic reactions, and only one of them was able to resume the treatment.

Adjuvant therapy with trastuzumab plus paclitaxel yielded a 3-year recurrence rate of < 2% in an uncontrolled, nonrandomized study involving women who had small stage I HER2-positive breast cancers, according to a report published online Jan. 8 in the New England Journal of Medicine.

Currently no standard treatment is recommended for such patients, and clinicians must weigh the generally favorable outcomes for small, stage I tumors that aren’t targeted with adjuvant chemotherapy against the potential for considerable toxic effects from adjuvant chemotherapy. Clinical trials of trastuzumab have focused on patients with more advanced cancers. “Although patients with stage I HER2-positive tumors are expected to derive a smaller absolute benefit from adjuvant therapy than those with larger or node-positive tumors, they remain at more than minimal risk for a recurrence of breast cancer,” said Dr. Sara M. Tolaney of the department of medical oncology, Dana-Farber Cancer Institute, Boston, and her associates.

Their industry-sponsored single-group study involved 406 patients with a median age of 55 years (range, 24-85 years) whose breast adenocarcinomas measured no more than 3 cm. After undergoing surgical excisions, all the study participants were assigned to receive weekly IV paclitaxel and IV trastuzumab for 12 weeks, after which trastuzumab could be continued at the same weekly dose for 40 weeks or the regimen could be changed to a slightly higher dose every 3 weeks for 40 weeks.

A total of 356 patients (87.7%) completed the full year of adjuvant trastuzumab. Women who opted for partial- or whole-breast irradiation commenced that treatment after completing paclitaxel and while taking trastuzumab, and those who chose hormonal therapy also began taking those agents after completing paclitaxel and while taking trastuzumab. Median follow-up was 4 years (maximum, 6.2 years).

At 3-year follow-up, the rate of cancer-free survival was 98.7%, which was higher than would have been predicted by historical data; there were four distant and four local or regional metastases. According to the study’s statistical design, adjuvant trastuzumab would be considered successful if the 3-year recurrence rate were 5% or lower and there were 39 or fewer metastases, Dr. Tolaney and her associates said (N. Engl. J. Med. 2015 Jan. 8 [doi:10.1056/NEJM0a1406281]).

A total of 6% of patients withdrew from the study because of treatment-related adverse effects. The most important known adverse effect of trastuzumab is left ventricular dysfunction, so cardiac function was assessed at several intervals during the year of active therapy. Two patients (0.5%) developed grade 3 LV dysfunction during treatment, and both recovered after the drug was discontinued. Thirteen patients (3.2%) showed an asymptomatic decline in ejection fraction that led to an interruption in trastuzumab therapy; this normalized in 11 of them, who then resumed the treatment. Seven patients developed grade 3 or 4 allergic reactions, and only one of them was able to resume the treatment.

Adjuvant therapy with trastuzumab plus paclitaxel yielded a 3-year recurrence rate of < 2% in an uncontrolled, nonrandomized study involving women who had small stage I HER2-positive breast cancers, according to a report published online Jan. 8 in the New England Journal of Medicine.

Currently no standard treatment is recommended for such patients, and clinicians must weigh the generally favorable outcomes for small, stage I tumors that aren’t targeted with adjuvant chemotherapy against the potential for considerable toxic effects from adjuvant chemotherapy. Clinical trials of trastuzumab have focused on patients with more advanced cancers. “Although patients with stage I HER2-positive tumors are expected to derive a smaller absolute benefit from adjuvant therapy than those with larger or node-positive tumors, they remain at more than minimal risk for a recurrence of breast cancer,” said Dr. Sara M. Tolaney of the department of medical oncology, Dana-Farber Cancer Institute, Boston, and her associates.

Their industry-sponsored single-group study involved 406 patients with a median age of 55 years (range, 24-85 years) whose breast adenocarcinomas measured no more than 3 cm. After undergoing surgical excisions, all the study participants were assigned to receive weekly IV paclitaxel and IV trastuzumab for 12 weeks, after which trastuzumab could be continued at the same weekly dose for 40 weeks or the regimen could be changed to a slightly higher dose every 3 weeks for 40 weeks.

A total of 356 patients (87.7%) completed the full year of adjuvant trastuzumab. Women who opted for partial- or whole-breast irradiation commenced that treatment after completing paclitaxel and while taking trastuzumab, and those who chose hormonal therapy also began taking those agents after completing paclitaxel and while taking trastuzumab. Median follow-up was 4 years (maximum, 6.2 years).

At 3-year follow-up, the rate of cancer-free survival was 98.7%, which was higher than would have been predicted by historical data; there were four distant and four local or regional metastases. According to the study’s statistical design, adjuvant trastuzumab would be considered successful if the 3-year recurrence rate were 5% or lower and there were 39 or fewer metastases, Dr. Tolaney and her associates said (N. Engl. J. Med. 2015 Jan. 8 [doi:10.1056/NEJM0a1406281]).

A total of 6% of patients withdrew from the study because of treatment-related adverse effects. The most important known adverse effect of trastuzumab is left ventricular dysfunction, so cardiac function was assessed at several intervals during the year of active therapy. Two patients (0.5%) developed grade 3 LV dysfunction during treatment, and both recovered after the drug was discontinued. Thirteen patients (3.2%) showed an asymptomatic decline in ejection fraction that led to an interruption in trastuzumab therapy; this normalized in 11 of them, who then resumed the treatment. Seven patients developed grade 3 or 4 allergic reactions, and only one of them was able to resume the treatment.

SAN ANTONIO – Male breast cancers share some important characteristics with female breast cancers: The tumors found in males are usually hormone receptor positive and of luminal A subtype, and respond less favorably if estrogen and progesterone receptor negative.

And like female breast cancers, both overall and breast cancer–specific survival rates have been increasing over the last 20 years, although not to the extent of survival improvements in women, Dr. Fatima Cardoso said at the San Antonio Breast Cancer Symposium.

Michele G. Sullivan/Frontline Medical News

Dr. Cardoso of the European School of Oncology Breast Cancer Program, Lisbon, presented the initial findings of the Male Breast Cancer International Program, a project intended to identify, characterize, and improve treatment for male breast cancers. The retrospective joint analysis is the first part of the three-step study, she said. In addition to identifying patients in the 10 countries involved (in the United States, western Europe, and Scandinavia), step one includes a collection of tumor blocks for central analysis in labs in the United States and the Netherlands.

Step two, already underway, is building a prospective international registry of all male breast cancer cases in the most recent 30 months of the study, including collection of tumor samples and blood, and a quality of life substudy.

Step three will comprise randomized treatment trials, one of which is “far along in the planning stage,” Dr. Cardoso said.

The retrospective cohort comprised 1,822 men who were diagnosed and treated for breast cancer from 1990 to 2010, with tumor assessments available for 1,483. About two-thirds of the men were older than 50 years; 25% were 75 or older. Just 2% were younger than 40 years.

Most cancers (71%) were local. Almost 60% were node negative, and 30% positive for one node. Two nodes were involved in 5% and the rest had three involved.

Breast-conserving surgery was the most common primary treatment (96%), with 4% undergoing a modified radical mastectomy. Three-fourths underwent both a sentinel node biopsy and axillary dissection; 18% had a sentinel node biopsy only, and the rest had no nodal investigation. There was a slight trend over the study period for more sentinel node biopsies alone, and less axillary dissection, but the number of men without an investigation stayed steady.

After breast-conserving surgery, all of the node-positive patients had adjuvant radiotherapy, as did 46% of the node-negative patients. Of the node-positive patients who had mastectomy, 69% received radiotherapy and 31% did not.

Adjuvant chemotherapy was administered to 70% of patients overall, with anthracyclines the most commonly used agent (43%). Others were the combination of anthracyclines and taxanes (32%); the combination of cyclophosphamide, methotrexate and fluorouracil (15%); and other unspecified regimens in the remainder.

Most men also received endocrine therapy (77%), with tamoxifen being the most common agent (88%).

Invasive ductal carcinoma was by far the most common diagnosis (about 85%). About half the tumors were grade 2; the rest were evenly split between grades 1 and 3.

The vast majority (1,053) were estrogen receptor positive with 93% having high expression. Progesterone receptor positivity occurred in 939 tumors, with 35% having high expression.

Most of the tumors were positive for androgen expression (1,027), again with high expression (88%). Two percent were human epidermal growth factor 2 (HER2) positive.

Not surprisingly, median overall survival was best in patients with nonmetastatic, nonnodal cancers (10.4 years). It was about 8.4 years for those with nonmetastatic, node-positive tumors, and 2.6 years for those with metastatic cancers.

Median overall mortality has significantly decreased over the years: About 70% of those diagnosed from 1990 to 1995 had died within 9 years, compared to about 40% of those diagnosed from 2006 to 2010. But breast cancer–specific mortality remained about the same, with less than 20% of patients dying by the end of follow-up.

Those with estrogen receptor–positive tumors did best, especially if they had high expression, while all of those with ER-negative tumors had died by 6 years after diagnosis. Findings were similar among those with androgen and progesterone receptor–negative tumors.

“Hormone receptor status had a very good prognostic value, with positive, highly expressed tumors having much better outcomes,” Dr. Cardoso said, adding that tumors in this initial phase of the study are still being examined.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN ANTONIO – Male breast cancers share some important characteristics with female breast cancers: The tumors found in males are usually hormone receptor positive and of luminal A subtype, and respond less favorably if estrogen and progesterone receptor negative.

And like female breast cancers, both overall and breast cancer–specific survival rates have been increasing over the last 20 years, although not to the extent of survival improvements in women, Dr. Fatima Cardoso said at the San Antonio Breast Cancer Symposium.

Michele G. Sullivan/Frontline Medical News

Dr. Cardoso of the European School of Oncology Breast Cancer Program, Lisbon, presented the initial findings of the Male Breast Cancer International Program, a project intended to identify, characterize, and improve treatment for male breast cancers. The retrospective joint analysis is the first part of the three-step study, she said. In addition to identifying patients in the 10 countries involved (in the United States, western Europe, and Scandinavia), step one includes a collection of tumor blocks for central analysis in labs in the United States and the Netherlands.

Step two, already underway, is building a prospective international registry of all male breast cancer cases in the most recent 30 months of the study, including collection of tumor samples and blood, and a quality of life substudy.

Step three will comprise randomized treatment trials, one of which is “far along in the planning stage,” Dr. Cardoso said.

The retrospective cohort comprised 1,822 men who were diagnosed and treated for breast cancer from 1990 to 2010, with tumor assessments available for 1,483. About two-thirds of the men were older than 50 years; 25% were 75 or older. Just 2% were younger than 40 years.

Most cancers (71%) were local. Almost 60% were node negative, and 30% positive for one node. Two nodes were involved in 5% and the rest had three involved.

Breast-conserving surgery was the most common primary treatment (96%), with 4% undergoing a modified radical mastectomy. Three-fourths underwent both a sentinel node biopsy and axillary dissection; 18% had a sentinel node biopsy only, and the rest had no nodal investigation. There was a slight trend over the study period for more sentinel node biopsies alone, and less axillary dissection, but the number of men without an investigation stayed steady.

After breast-conserving surgery, all of the node-positive patients had adjuvant radiotherapy, as did 46% of the node-negative patients. Of the node-positive patients who had mastectomy, 69% received radiotherapy and 31% did not.

Adjuvant chemotherapy was administered to 70% of patients overall, with anthracyclines the most commonly used agent (43%). Others were the combination of anthracyclines and taxanes (32%); the combination of cyclophosphamide, methotrexate and fluorouracil (15%); and other unspecified regimens in the remainder.

Most men also received endocrine therapy (77%), with tamoxifen being the most common agent (88%).

Invasive ductal carcinoma was by far the most common diagnosis (about 85%). About half the tumors were grade 2; the rest were evenly split between grades 1 and 3.

The vast majority (1,053) were estrogen receptor positive with 93% having high expression. Progesterone receptor positivity occurred in 939 tumors, with 35% having high expression.

Most of the tumors were positive for androgen expression (1,027), again with high expression (88%). Two percent were human epidermal growth factor 2 (HER2) positive.

Not surprisingly, median overall survival was best in patients with nonmetastatic, nonnodal cancers (10.4 years). It was about 8.4 years for those with nonmetastatic, node-positive tumors, and 2.6 years for those with metastatic cancers.

Median overall mortality has significantly decreased over the years: About 70% of those diagnosed from 1990 to 1995 had died within 9 years, compared to about 40% of those diagnosed from 2006 to 2010. But breast cancer–specific mortality remained about the same, with less than 20% of patients dying by the end of follow-up.

Those with estrogen receptor–positive tumors did best, especially if they had high expression, while all of those with ER-negative tumors had died by 6 years after diagnosis. Findings were similar among those with androgen and progesterone receptor–negative tumors.

“Hormone receptor status had a very good prognostic value, with positive, highly expressed tumors having much better outcomes,” Dr. Cardoso said, adding that tumors in this initial phase of the study are still being examined.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN ANTONIO – Male breast cancers share some important characteristics with female breast cancers: The tumors found in males are usually hormone receptor positive and of luminal A subtype, and respond less favorably if estrogen and progesterone receptor negative.

And like female breast cancers, both overall and breast cancer–specific survival rates have been increasing over the last 20 years, although not to the extent of survival improvements in women, Dr. Fatima Cardoso said at the San Antonio Breast Cancer Symposium.

Michele G. Sullivan/Frontline Medical News

Dr. Cardoso of the European School of Oncology Breast Cancer Program, Lisbon, presented the initial findings of the Male Breast Cancer International Program, a project intended to identify, characterize, and improve treatment for male breast cancers. The retrospective joint analysis is the first part of the three-step study, she said. In addition to identifying patients in the 10 countries involved (in the United States, western Europe, and Scandinavia), step one includes a collection of tumor blocks for central analysis in labs in the United States and the Netherlands.

Step two, already underway, is building a prospective international registry of all male breast cancer cases in the most recent 30 months of the study, including collection of tumor samples and blood, and a quality of life substudy.

Step three will comprise randomized treatment trials, one of which is “far along in the planning stage,” Dr. Cardoso said.

The retrospective cohort comprised 1,822 men who were diagnosed and treated for breast cancer from 1990 to 2010, with tumor assessments available for 1,483. About two-thirds of the men were older than 50 years; 25% were 75 or older. Just 2% were younger than 40 years.

Most cancers (71%) were local. Almost 60% were node negative, and 30% positive for one node. Two nodes were involved in 5% and the rest had three involved.

Breast-conserving surgery was the most common primary treatment (96%), with 4% undergoing a modified radical mastectomy. Three-fourths underwent both a sentinel node biopsy and axillary dissection; 18% had a sentinel node biopsy only, and the rest had no nodal investigation. There was a slight trend over the study period for more sentinel node biopsies alone, and less axillary dissection, but the number of men without an investigation stayed steady.

After breast-conserving surgery, all of the node-positive patients had adjuvant radiotherapy, as did 46% of the node-negative patients. Of the node-positive patients who had mastectomy, 69% received radiotherapy and 31% did not.

Adjuvant chemotherapy was administered to 70% of patients overall, with anthracyclines the most commonly used agent (43%). Others were the combination of anthracyclines and taxanes (32%); the combination of cyclophosphamide, methotrexate and fluorouracil (15%); and other unspecified regimens in the remainder.

Most men also received endocrine therapy (77%), with tamoxifen being the most common agent (88%).

Invasive ductal carcinoma was by far the most common diagnosis (about 85%). About half the tumors were grade 2; the rest were evenly split between grades 1 and 3.

The vast majority (1,053) were estrogen receptor positive with 93% having high expression. Progesterone receptor positivity occurred in 939 tumors, with 35% having high expression.

Most of the tumors were positive for androgen expression (1,027), again with high expression (88%). Two percent were human epidermal growth factor 2 (HER2) positive.

Not surprisingly, median overall survival was best in patients with nonmetastatic, nonnodal cancers (10.4 years). It was about 8.4 years for those with nonmetastatic, node-positive tumors, and 2.6 years for those with metastatic cancers.

Median overall mortality has significantly decreased over the years: About 70% of those diagnosed from 1990 to 1995 had died within 9 years, compared to about 40% of those diagnosed from 2006 to 2010. But breast cancer–specific mortality remained about the same, with less than 20% of patients dying by the end of follow-up.

Those with estrogen receptor–positive tumors did best, especially if they had high expression, while all of those with ER-negative tumors had died by 6 years after diagnosis. Findings were similar among those with androgen and progesterone receptor–negative tumors.

“Hormone receptor status had a very good prognostic value, with positive, highly expressed tumors having much better outcomes,” Dr. Cardoso said, adding that tumors in this initial phase of the study are still being examined.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

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

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

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

Michele G. Sullivan/Frontline Medical News

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

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

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

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

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

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

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

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

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

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

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

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

Michele G. Sullivan/Frontline Medical News

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

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

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

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

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

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

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

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

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

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

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

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

Michele G. Sullivan/Frontline Medical News

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

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

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

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

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

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

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

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

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

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

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

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

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

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

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

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

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

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

She reported having no financial conflicts regarding this study.

bjancin@frontlinemedcom.com

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

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

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

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

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

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

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

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

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

She reported having no financial conflicts regarding this study.

bjancin@frontlinemedcom.com

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

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

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

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

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

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

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

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

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

She reported having no financial conflicts regarding this study.

bjancin@frontlinemedcom.com

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Hurvitz concurred.

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

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

bjancin@frontlinemedcom.com

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Hurvitz concurred.

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

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

bjancin@frontlinemedcom.com

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Hurvitz concurred.

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

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

bjancin@frontlinemedcom.com