Breast Cancer

Dr. David H. Henry takes you on an audio tour of the December issue of Community Oncology, which includes a discussion and commentary on adding regional nodal irradiation to whole-breast irradiation to improve disease-free survival in breast cancer patient. Other podcast features includes highlights from the San Antonio Breast Cancer Symposium, the International Society of Geriatric Oncology and the Radiological Society of North America.

Dr. David H. Henry takes you on an audio tour of the December issue of Community Oncology, which includes a discussion and commentary on adding regional nodal irradiation to whole-breast irradiation to improve disease-free survival in breast cancer patient. Other podcast features includes highlights from the San Antonio Breast Cancer Symposium, the International Society of Geriatric Oncology and the Radiological Society of North America.

Dr. David H. Henry takes you on an audio tour of the December issue of Community Oncology, which includes a discussion and commentary on adding regional nodal irradiation to whole-breast irradiation to improve disease-free survival in breast cancer patient. Other podcast features includes highlights from the San Antonio Breast Cancer Symposium, the International Society of Geriatric Oncology and the Radiological Society of North America.

SAN ANTONIO – The combination of topical 5% imiquimod plus systemic nanoparticle albumin-bound paclitaxel showed excellent clinical efficacy and was well tolerated for the treatment of cutaneous metastases of breast cancer in a phase II study.

Among the 11 patients who were able to complete the novel combined chemoimmunotherapy regimen, 5 had a complete response, meaning 100% clearance of treated skin lesions at week 24.

In addition, one patient had a partial response, defined as a greater than 50% reduction in the size of the largest treated lesion. Four patients had stable disease, with less than 50% reductions in lesion size. One patient experienced progressive disease, with a 25% increase in target lesion size, Dr. Lupe G. Salazar reported at the San Antonio Breast Cancer Symposium.

Fifteen heavily pretreated breast cancer patients were enrolled in the single-arm, nonrandomized study. All had skin metastases no longer amenable to standard therapies.

The chemoimmunotherapy regimen consisted of three treatment cycles. Each 4-week cycle consisted of application of topical 5% imiquimod to target cutaneous lesions on 4 days per week plus systemic albumin-bound paclitaxel (Abraxane) at 100 mg/m² on days 1, 8, 15, and 28, explained Dr. Salazar of the University of Washington, Seattle.

Treatment-related toxicities included neutropenia, lymphopenia, anemia, nausea, and fatigue; 34% of toxicities were grade 1, 56% were grade 2, and the remaining 10% were grade 3.

Four of 15 subjects were unable to complete the treatment regimen, having withdrawn due to progression of visceral disease.

The rationale for the imiquimod plus nanoparticle albumin-bound (nab) paclitaxel (Abraxane) therapy derives from previous evidence that imiquimod, a toll-like receptor-7 agonist, has shown clinical efficacy against cutaneous metastases. Imiquimod stimulates secretion of Th1 cytokines and upregulates immune costimulatory molecules at the tumor site. Tumor-specific T cell immunity and tumor growth inhibition are enhanced. Moreover, paclitaxel has been shown to increase serum interferon-gamma levels and boost natural killer cell activity. Thus, the working hypothesis was that nab-paclitaxel would augment imiquimod’s antitumor effects, according to Dr. Salazar.

She and her coinvestigators examined the combination therapy’s impact upon endogenous tumor-specific immunity. They obtained pre- and posttreatment 2-mm skin biopsies from target lesions and were able to demonstrate that the treatment marginally enhanced endogenous immunity to the well-known breast cancer antigens HER2, p53, melanoma-associated antigen 3 (MAGE-3), insulin growth factor binding protein-2 (IGFBP-2), and topoisomerase IIa (TOPO-IIa).

The study was funded by a grant from the National Cancer Institute. Dr. Salazar declared having no relevant financial interests.

SAN ANTONIO – The combination of topical 5% imiquimod plus systemic nanoparticle albumin-bound paclitaxel showed excellent clinical efficacy and was well tolerated for the treatment of cutaneous metastases of breast cancer in a phase II study.

Among the 11 patients who were able to complete the novel combined chemoimmunotherapy regimen, 5 had a complete response, meaning 100% clearance of treated skin lesions at week 24.

In addition, one patient had a partial response, defined as a greater than 50% reduction in the size of the largest treated lesion. Four patients had stable disease, with less than 50% reductions in lesion size. One patient experienced progressive disease, with a 25% increase in target lesion size, Dr. Lupe G. Salazar reported at the San Antonio Breast Cancer Symposium.

Fifteen heavily pretreated breast cancer patients were enrolled in the single-arm, nonrandomized study. All had skin metastases no longer amenable to standard therapies.

The chemoimmunotherapy regimen consisted of three treatment cycles. Each 4-week cycle consisted of application of topical 5% imiquimod to target cutaneous lesions on 4 days per week plus systemic albumin-bound paclitaxel (Abraxane) at 100 mg/m² on days 1, 8, 15, and 28, explained Dr. Salazar of the University of Washington, Seattle.

Treatment-related toxicities included neutropenia, lymphopenia, anemia, nausea, and fatigue; 34% of toxicities were grade 1, 56% were grade 2, and the remaining 10% were grade 3.

Four of 15 subjects were unable to complete the treatment regimen, having withdrawn due to progression of visceral disease.

The rationale for the imiquimod plus nanoparticle albumin-bound (nab) paclitaxel (Abraxane) therapy derives from previous evidence that imiquimod, a toll-like receptor-7 agonist, has shown clinical efficacy against cutaneous metastases. Imiquimod stimulates secretion of Th1 cytokines and upregulates immune costimulatory molecules at the tumor site. Tumor-specific T cell immunity and tumor growth inhibition are enhanced. Moreover, paclitaxel has been shown to increase serum interferon-gamma levels and boost natural killer cell activity. Thus, the working hypothesis was that nab-paclitaxel would augment imiquimod’s antitumor effects, according to Dr. Salazar.

She and her coinvestigators examined the combination therapy’s impact upon endogenous tumor-specific immunity. They obtained pre- and posttreatment 2-mm skin biopsies from target lesions and were able to demonstrate that the treatment marginally enhanced endogenous immunity to the well-known breast cancer antigens HER2, p53, melanoma-associated antigen 3 (MAGE-3), insulin growth factor binding protein-2 (IGFBP-2), and topoisomerase IIa (TOPO-IIa).

The study was funded by a grant from the National Cancer Institute. Dr. Salazar declared having no relevant financial interests.

SAN ANTONIO – The combination of topical 5% imiquimod plus systemic nanoparticle albumin-bound paclitaxel showed excellent clinical efficacy and was well tolerated for the treatment of cutaneous metastases of breast cancer in a phase II study.

Among the 11 patients who were able to complete the novel combined chemoimmunotherapy regimen, 5 had a complete response, meaning 100% clearance of treated skin lesions at week 24.

In addition, one patient had a partial response, defined as a greater than 50% reduction in the size of the largest treated lesion. Four patients had stable disease, with less than 50% reductions in lesion size. One patient experienced progressive disease, with a 25% increase in target lesion size, Dr. Lupe G. Salazar reported at the San Antonio Breast Cancer Symposium.

Fifteen heavily pretreated breast cancer patients were enrolled in the single-arm, nonrandomized study. All had skin metastases no longer amenable to standard therapies.

The chemoimmunotherapy regimen consisted of three treatment cycles. Each 4-week cycle consisted of application of topical 5% imiquimod to target cutaneous lesions on 4 days per week plus systemic albumin-bound paclitaxel (Abraxane) at 100 mg/m² on days 1, 8, 15, and 28, explained Dr. Salazar of the University of Washington, Seattle.

Treatment-related toxicities included neutropenia, lymphopenia, anemia, nausea, and fatigue; 34% of toxicities were grade 1, 56% were grade 2, and the remaining 10% were grade 3.

Four of 15 subjects were unable to complete the treatment regimen, having withdrawn due to progression of visceral disease.

The rationale for the imiquimod plus nanoparticle albumin-bound (nab) paclitaxel (Abraxane) therapy derives from previous evidence that imiquimod, a toll-like receptor-7 agonist, has shown clinical efficacy against cutaneous metastases. Imiquimod stimulates secretion of Th1 cytokines and upregulates immune costimulatory molecules at the tumor site. Tumor-specific T cell immunity and tumor growth inhibition are enhanced. Moreover, paclitaxel has been shown to increase serum interferon-gamma levels and boost natural killer cell activity. Thus, the working hypothesis was that nab-paclitaxel would augment imiquimod’s antitumor effects, according to Dr. Salazar.

She and her coinvestigators examined the combination therapy’s impact upon endogenous tumor-specific immunity. They obtained pre- and posttreatment 2-mm skin biopsies from target lesions and were able to demonstrate that the treatment marginally enhanced endogenous immunity to the well-known breast cancer antigens HER2, p53, melanoma-associated antigen 3 (MAGE-3), insulin growth factor binding protein-2 (IGFBP-2), and topoisomerase IIa (TOPO-IIa).

The study was funded by a grant from the National Cancer Institute. Dr. Salazar declared having no relevant financial interests.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

SAN ANTONIO – Physicians tend to broadly overestimate their own breast cancer patients’ compliance with adjuvant aromatase inhibitor therapy, according to a large observational German study.

Among 2,313 postmenopausal breast cancer patients who were enrolled in the ongoing COMPACT (Compliance and Arthralgias in Clinical Therapy) study, 80.5% stated that they took all or nearly all of their prescribed anastrozole tablets during their first year on adjuvant endocrine therapy.

In contrast, 93.2% of their oncologists indicated they believed those same patients had taken all or nearly all of their medication, Dr. Peyman Hadji reported at the San Antonio Breast Cancer Symposium.

Among COMPACT participants, 11.9% indicated that they experienced pre-existing arthralgias within 4 weeks prior to going on the aromatase inhibitor. Another 17% reported new-onset arthralgias after starting on anastrozole, according to Dr. Hadji of the University Hospital of Giessen and Marburg (Germany) GmbH.

Session chair Dr. Thomas J. Smith said that these initial data from the COMPACT study contain a key take-home message: "I think it certainly behooves me as a breast cancer doctor to ask every time, ‘Are you having trouble with these drugs?’ because people do have trouble with these drugs, and they don’t want to bother us."

Another take-home point is that although roughly 12% of breast cancer patients have pre-existing arthralgias, the prescription of an aromatase inhibitor increases the population of affected individuals by close to an absolute 20%, added Dr. Smith, director of palliative care and professor of oncology at Johns Hopkins University, Baltimore.

Dr. Hadji said that going forward, COMPACT will assess the frequency and severity of aromatase inhibitor–associated arthralgias in real-world clinical practice, will chart rates of arthralgia-related treatment noncompliance, and will document the effectiveness and costs of various treatments.

Dr. Smith observed that to date there is a noteworthy lack of good-quality, randomized trial data to guide treatment of aromatase inhibitor–associated arthralgias. Dr. Hadji concurred. He said he and his colleagues have had favorable experiences using NSAIDs, but that’s anecdotal experience. Regarding high-quality data, he cited what he termed a "wonderful" double-blind study showing benefit for acupuncture (J. Clin. Oncol. 2010;28:1154-60).

"The data were really fascinating, but we couldn’t find anybody in our clinic to start doing it. For whatever reasons, oncologists don’t like putting needles into patients," he quipped.

The COMPACT study is sponsored by AstraZeneca. Dr. Hadji serves as a consultant to the company.

SAN ANTONIO – Physicians tend to broadly overestimate their own breast cancer patients’ compliance with adjuvant aromatase inhibitor therapy, according to a large observational German study.

Among 2,313 postmenopausal breast cancer patients who were enrolled in the ongoing COMPACT (Compliance and Arthralgias in Clinical Therapy) study, 80.5% stated that they took all or nearly all of their prescribed anastrozole tablets during their first year on adjuvant endocrine therapy.

In contrast, 93.2% of their oncologists indicated they believed those same patients had taken all or nearly all of their medication, Dr. Peyman Hadji reported at the San Antonio Breast Cancer Symposium.

Among COMPACT participants, 11.9% indicated that they experienced pre-existing arthralgias within 4 weeks prior to going on the aromatase inhibitor. Another 17% reported new-onset arthralgias after starting on anastrozole, according to Dr. Hadji of the University Hospital of Giessen and Marburg (Germany) GmbH.

Session chair Dr. Thomas J. Smith said that these initial data from the COMPACT study contain a key take-home message: "I think it certainly behooves me as a breast cancer doctor to ask every time, ‘Are you having trouble with these drugs?’ because people do have trouble with these drugs, and they don’t want to bother us."

Another take-home point is that although roughly 12% of breast cancer patients have pre-existing arthralgias, the prescription of an aromatase inhibitor increases the population of affected individuals by close to an absolute 20%, added Dr. Smith, director of palliative care and professor of oncology at Johns Hopkins University, Baltimore.

Dr. Hadji said that going forward, COMPACT will assess the frequency and severity of aromatase inhibitor–associated arthralgias in real-world clinical practice, will chart rates of arthralgia-related treatment noncompliance, and will document the effectiveness and costs of various treatments.

Dr. Smith observed that to date there is a noteworthy lack of good-quality, randomized trial data to guide treatment of aromatase inhibitor–associated arthralgias. Dr. Hadji concurred. He said he and his colleagues have had favorable experiences using NSAIDs, but that’s anecdotal experience. Regarding high-quality data, he cited what he termed a "wonderful" double-blind study showing benefit for acupuncture (J. Clin. Oncol. 2010;28:1154-60).

"The data were really fascinating, but we couldn’t find anybody in our clinic to start doing it. For whatever reasons, oncologists don’t like putting needles into patients," he quipped.

The COMPACT study is sponsored by AstraZeneca. Dr. Hadji serves as a consultant to the company.

SAN ANTONIO – Physicians tend to broadly overestimate their own breast cancer patients’ compliance with adjuvant aromatase inhibitor therapy, according to a large observational German study.

Among 2,313 postmenopausal breast cancer patients who were enrolled in the ongoing COMPACT (Compliance and Arthralgias in Clinical Therapy) study, 80.5% stated that they took all or nearly all of their prescribed anastrozole tablets during their first year on adjuvant endocrine therapy.

In contrast, 93.2% of their oncologists indicated they believed those same patients had taken all or nearly all of their medication, Dr. Peyman Hadji reported at the San Antonio Breast Cancer Symposium.

Among COMPACT participants, 11.9% indicated that they experienced pre-existing arthralgias within 4 weeks prior to going on the aromatase inhibitor. Another 17% reported new-onset arthralgias after starting on anastrozole, according to Dr. Hadji of the University Hospital of Giessen and Marburg (Germany) GmbH.

Session chair Dr. Thomas J. Smith said that these initial data from the COMPACT study contain a key take-home message: "I think it certainly behooves me as a breast cancer doctor to ask every time, ‘Are you having trouble with these drugs?’ because people do have trouble with these drugs, and they don’t want to bother us."

Another take-home point is that although roughly 12% of breast cancer patients have pre-existing arthralgias, the prescription of an aromatase inhibitor increases the population of affected individuals by close to an absolute 20%, added Dr. Smith, director of palliative care and professor of oncology at Johns Hopkins University, Baltimore.

Dr. Hadji said that going forward, COMPACT will assess the frequency and severity of aromatase inhibitor–associated arthralgias in real-world clinical practice, will chart rates of arthralgia-related treatment noncompliance, and will document the effectiveness and costs of various treatments.

Dr. Smith observed that to date there is a noteworthy lack of good-quality, randomized trial data to guide treatment of aromatase inhibitor–associated arthralgias. Dr. Hadji concurred. He said he and his colleagues have had favorable experiences using NSAIDs, but that’s anecdotal experience. Regarding high-quality data, he cited what he termed a "wonderful" double-blind study showing benefit for acupuncture (J. Clin. Oncol. 2010;28:1154-60).

"The data were really fascinating, but we couldn’t find anybody in our clinic to start doing it. For whatever reasons, oncologists don’t like putting needles into patients," he quipped.

The COMPACT study is sponsored by AstraZeneca. Dr. Hadji serves as a consultant to the company.

SAN ANTONIO – Trastuzumab emtansine – the novel antibody-drug conjugate known as T-DM1 – provides significantly greater patient-reported quality of life and treatment tolerability than do standard trastuzumab and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer, a phase II study indicates.

This is the same randomized, multicenter, open-label, phase II study that previously reported a highly significant 41% improvement in the efficacy end point of investigator-reported progression-free survival favoring trastuzumab emtansine by a margin of 14.2 months vs. 9.2 months, Dr. Giulia V. Bianchi noted at the annual San Antonio Breast Cancer Symposium.

Her new report presented key patient-reported outcomes, such as quality of life measurements. These data further define T-DM1 as a therapy that’s superior to what’s currently available, according to Dr. Bianchi of the Italian National Cancer Institute, Milan.

The primary patient-reported outcome was time to symptom progression (defined by at least a 5-point decrease from baseline on the Functional Assessment of Cancer Therapy–Breast Trial Outcome Index). Among 132 evaluable study participants, worsening of the FACT-B TOI score was significantly delayed in patients who were randomized to T-DM1; it occurred at a mean of 7.5 months in these patients, compared with 3.5 months in subjects assigned to trastuzumab (Herceptin) plus docetaxel (Taxotere).

The chief benefit of T-DM1 showed up on the physical well being subscale of the FACT-B TOI. Five of the seven items on the physical well-being subscale (lack of energy, feel ill, trouble meeting needs of family, bothered by side effects, and forced to spend time in bed) showed significantly better mean scores with T-DM1. The other two physical well-being items (nausea and pain) trended better in the T-DM1 group, but not significantly so.

The incidence of grade 3 or greater adverse events was 46% in the T-DM1 group vs. 89% in controls. Only 7% of patients in the T-DM1 arm stopped therapy because of adverse events, compared with 30% in the trastuzumab-plus-docetaxel arm.

Taken together, these data support the notion that T-DM1 is an advance in terms of tolerability, which in turn contributes to enhanced efficacy, safety, and health-related quality of life, Dr. Bianchi concluded.

The phase II study was sponsored by Genentech, which has big plans for T-DM1. The phase III MARIANNE trial, which is comparing T-DM1 as single-agent therapy with T-DM1 plus pertuzumab and with various trastuzumab/taxane combinations as first-line therapy in advanced HER2-positive breast cancer, is well underway. The phase III EMILIA trial is looking at T-DM1 for second-line use in advanced HER2-positive breast cancer. In addition, the monoclonal antibody and drug conjugate is under development for adjuvant and neoadjuvant use in early-stage breast cancer. T-DM1 is also being scrutinized as a potential treatment for HER2-positive gastric cancer.

Dr. Bianchi declared she has no financial conflicts of interest.

SAN ANTONIO – Trastuzumab emtansine – the novel antibody-drug conjugate known as T-DM1 – provides significantly greater patient-reported quality of life and treatment tolerability than do standard trastuzumab and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer, a phase II study indicates.

This is the same randomized, multicenter, open-label, phase II study that previously reported a highly significant 41% improvement in the efficacy end point of investigator-reported progression-free survival favoring trastuzumab emtansine by a margin of 14.2 months vs. 9.2 months, Dr. Giulia V. Bianchi noted at the annual San Antonio Breast Cancer Symposium.

Her new report presented key patient-reported outcomes, such as quality of life measurements. These data further define T-DM1 as a therapy that’s superior to what’s currently available, according to Dr. Bianchi of the Italian National Cancer Institute, Milan.

The primary patient-reported outcome was time to symptom progression (defined by at least a 5-point decrease from baseline on the Functional Assessment of Cancer Therapy–Breast Trial Outcome Index). Among 132 evaluable study participants, worsening of the FACT-B TOI score was significantly delayed in patients who were randomized to T-DM1; it occurred at a mean of 7.5 months in these patients, compared with 3.5 months in subjects assigned to trastuzumab (Herceptin) plus docetaxel (Taxotere).

The chief benefit of T-DM1 showed up on the physical well being subscale of the FACT-B TOI. Five of the seven items on the physical well-being subscale (lack of energy, feel ill, trouble meeting needs of family, bothered by side effects, and forced to spend time in bed) showed significantly better mean scores with T-DM1. The other two physical well-being items (nausea and pain) trended better in the T-DM1 group, but not significantly so.

The incidence of grade 3 or greater adverse events was 46% in the T-DM1 group vs. 89% in controls. Only 7% of patients in the T-DM1 arm stopped therapy because of adverse events, compared with 30% in the trastuzumab-plus-docetaxel arm.

Taken together, these data support the notion that T-DM1 is an advance in terms of tolerability, which in turn contributes to enhanced efficacy, safety, and health-related quality of life, Dr. Bianchi concluded.

The phase II study was sponsored by Genentech, which has big plans for T-DM1. The phase III MARIANNE trial, which is comparing T-DM1 as single-agent therapy with T-DM1 plus pertuzumab and with various trastuzumab/taxane combinations as first-line therapy in advanced HER2-positive breast cancer, is well underway. The phase III EMILIA trial is looking at T-DM1 for second-line use in advanced HER2-positive breast cancer. In addition, the monoclonal antibody and drug conjugate is under development for adjuvant and neoadjuvant use in early-stage breast cancer. T-DM1 is also being scrutinized as a potential treatment for HER2-positive gastric cancer.

Dr. Bianchi declared she has no financial conflicts of interest.

SAN ANTONIO – Trastuzumab emtansine – the novel antibody-drug conjugate known as T-DM1 – provides significantly greater patient-reported quality of life and treatment tolerability than do standard trastuzumab and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer, a phase II study indicates.

This is the same randomized, multicenter, open-label, phase II study that previously reported a highly significant 41% improvement in the efficacy end point of investigator-reported progression-free survival favoring trastuzumab emtansine by a margin of 14.2 months vs. 9.2 months, Dr. Giulia V. Bianchi noted at the annual San Antonio Breast Cancer Symposium.

Her new report presented key patient-reported outcomes, such as quality of life measurements. These data further define T-DM1 as a therapy that’s superior to what’s currently available, according to Dr. Bianchi of the Italian National Cancer Institute, Milan.

The primary patient-reported outcome was time to symptom progression (defined by at least a 5-point decrease from baseline on the Functional Assessment of Cancer Therapy–Breast Trial Outcome Index). Among 132 evaluable study participants, worsening of the FACT-B TOI score was significantly delayed in patients who were randomized to T-DM1; it occurred at a mean of 7.5 months in these patients, compared with 3.5 months in subjects assigned to trastuzumab (Herceptin) plus docetaxel (Taxotere).

The chief benefit of T-DM1 showed up on the physical well being subscale of the FACT-B TOI. Five of the seven items on the physical well-being subscale (lack of energy, feel ill, trouble meeting needs of family, bothered by side effects, and forced to spend time in bed) showed significantly better mean scores with T-DM1. The other two physical well-being items (nausea and pain) trended better in the T-DM1 group, but not significantly so.

The incidence of grade 3 or greater adverse events was 46% in the T-DM1 group vs. 89% in controls. Only 7% of patients in the T-DM1 arm stopped therapy because of adverse events, compared with 30% in the trastuzumab-plus-docetaxel arm.

Taken together, these data support the notion that T-DM1 is an advance in terms of tolerability, which in turn contributes to enhanced efficacy, safety, and health-related quality of life, Dr. Bianchi concluded.

The phase II study was sponsored by Genentech, which has big plans for T-DM1. The phase III MARIANNE trial, which is comparing T-DM1 as single-agent therapy with T-DM1 plus pertuzumab and with various trastuzumab/taxane combinations as first-line therapy in advanced HER2-positive breast cancer, is well underway. The phase III EMILIA trial is looking at T-DM1 for second-line use in advanced HER2-positive breast cancer. In addition, the monoclonal antibody and drug conjugate is under development for adjuvant and neoadjuvant use in early-stage breast cancer. T-DM1 is also being scrutinized as a potential treatment for HER2-positive gastric cancer.

Dr. Bianchi declared she has no financial conflicts of interest.

HOT SPRINGS, VA. – An analysis of a prospectively collected database indicates that breast cancer patients with multiple nodal disease need a metastatic work-up only if they have tumor grade 3 or 4.

Current NCCN (National Comprehensive Cancer Network) guidelines recommend that patients with stage III and node-positive disease receive a work-up if they are N1. But the NCCN guidelines are less clear about what to do about N2 and N3 patients, said Dr. Quyen Chu at the annual meeting of the Southern Surgical Association.

About 20% of patients with stage III disease will have distant metastases, said Dr. Chu, chief of the surgical oncology division at Louisiana State University Health Sciences Center, Shreveport.

He and his colleagues at LSU extracted data from an ongoing, prospective breast cancer database, which was created in 1998 and comprises patient experience primarily from the LSU center but also from E.A. Conway Hospital in Monroe, La. They analyzed 256 patients with N2 or N3 disease who began treatment in 2010.

There was little difference between the two groups. The mean age of the 158 N2 patients was 58 years; it was 57 for the 68 N3 patients. The mean tumor grade was 2.5, and the mean tumor size was 4.6 cm. The tumor stage was similar between the two groups, with about 40% overall staged at T2.

"Are we risking an observation based on the play of chance?"

About half of the tumors were estrogen receptor positive overall. There was no difference in estrogen receptor status between the two groups. But more of the N3 patients had HER2-positive tumors, at 43% (31 of 72 patients), compared with 26% (27 of 103 patients) for the N2 group.

The primary end point for the study was the incidence of stage IV disease, either at the time of diagnosis or within 30 days of surgery. Patients underwent bone scans, CT, and/or PET to detect metastases.

Unexpectedly, the researchers found two T0 patients and 35 T1 patients who had stage III metastatic disease. The overall risk of stage IV disease was 16%. In all, 6% of T2 patients had stage IV disease, compared with 22% of T3 patients and 36% of T3 patients.

By N stage, about 83% of N2 and N3 patients had stage III disease, whereas 15% of each group had stage IV disease.

There was no difference in overall survival between the N2 and N3 groups, but those with stage IV disease had a predictably and statistically significant lower overall survival. Using a Cox proportional hazard model, the researchers determined that the only significant predictors of survival were T stage and grade.

Commenting on the paper, Dr. William C. Wood said that Dr. Chu’s observations were "unique," and that the data might help clinicians to more accurately judge tumor progression. "The rate of progression is very important to prognosis," said Dr. Wood, professor of surgery at Emory University in Atlanta. He cautioned, however, that the data set was small. Given that there was no difference in prognosis among the N2 and N3 groups, he asked, "Are we risking an observation based on the play of chance?"

Dr. Wood also suggested that there might not be any utility to identifying patients who had asymptomatic stage IV disease. Staging studies could be avoided, along with potential false positives, and the decision to not identify such patients "could avoid a longer period [of] awareness of stage IV disease in a person who could otherwise be blissfully unaware," he said.

Dr. Chu agreed that this was a valid question. But he suggested that newer agents and aggressive surgical intervention have been shown recently to potentially extend survival in stage IV disease.

Several other commentators wondered if the findings had prompted any change at LSU. "This paper by no means suggests we should change our standard of care," said Dr. Chu. It might prompt some review of the role of different imaging modalities used, he noted. And he added that the study should cause clinicians to question the biology of breast cancer.

"A lot of us have the preconceived notion that if you have N2 or N3 disease, [the] outcome is very bad. But in actuality, it may not be the case," he said. "You may have a subset [of patients] who do quite well, who are true stage III rather than stage IV."

Dr. Chu reported no conflicts.

HOT SPRINGS, VA. – An analysis of a prospectively collected database indicates that breast cancer patients with multiple nodal disease need a metastatic work-up only if they have tumor grade 3 or 4.

Current NCCN (National Comprehensive Cancer Network) guidelines recommend that patients with stage III and node-positive disease receive a work-up if they are N1. But the NCCN guidelines are less clear about what to do about N2 and N3 patients, said Dr. Quyen Chu at the annual meeting of the Southern Surgical Association.

About 20% of patients with stage III disease will have distant metastases, said Dr. Chu, chief of the surgical oncology division at Louisiana State University Health Sciences Center, Shreveport.

He and his colleagues at LSU extracted data from an ongoing, prospective breast cancer database, which was created in 1998 and comprises patient experience primarily from the LSU center but also from E.A. Conway Hospital in Monroe, La. They analyzed 256 patients with N2 or N3 disease who began treatment in 2010.

There was little difference between the two groups. The mean age of the 158 N2 patients was 58 years; it was 57 for the 68 N3 patients. The mean tumor grade was 2.5, and the mean tumor size was 4.6 cm. The tumor stage was similar between the two groups, with about 40% overall staged at T2.

"Are we risking an observation based on the play of chance?"

About half of the tumors were estrogen receptor positive overall. There was no difference in estrogen receptor status between the two groups. But more of the N3 patients had HER2-positive tumors, at 43% (31 of 72 patients), compared with 26% (27 of 103 patients) for the N2 group.

The primary end point for the study was the incidence of stage IV disease, either at the time of diagnosis or within 30 days of surgery. Patients underwent bone scans, CT, and/or PET to detect metastases.

Unexpectedly, the researchers found two T0 patients and 35 T1 patients who had stage III metastatic disease. The overall risk of stage IV disease was 16%. In all, 6% of T2 patients had stage IV disease, compared with 22% of T3 patients and 36% of T3 patients.

By N stage, about 83% of N2 and N3 patients had stage III disease, whereas 15% of each group had stage IV disease.

There was no difference in overall survival between the N2 and N3 groups, but those with stage IV disease had a predictably and statistically significant lower overall survival. Using a Cox proportional hazard model, the researchers determined that the only significant predictors of survival were T stage and grade.

Commenting on the paper, Dr. William C. Wood said that Dr. Chu’s observations were "unique," and that the data might help clinicians to more accurately judge tumor progression. "The rate of progression is very important to prognosis," said Dr. Wood, professor of surgery at Emory University in Atlanta. He cautioned, however, that the data set was small. Given that there was no difference in prognosis among the N2 and N3 groups, he asked, "Are we risking an observation based on the play of chance?"

Dr. Wood also suggested that there might not be any utility to identifying patients who had asymptomatic stage IV disease. Staging studies could be avoided, along with potential false positives, and the decision to not identify such patients "could avoid a longer period [of] awareness of stage IV disease in a person who could otherwise be blissfully unaware," he said.

Dr. Chu agreed that this was a valid question. But he suggested that newer agents and aggressive surgical intervention have been shown recently to potentially extend survival in stage IV disease.

Several other commentators wondered if the findings had prompted any change at LSU. "This paper by no means suggests we should change our standard of care," said Dr. Chu. It might prompt some review of the role of different imaging modalities used, he noted. And he added that the study should cause clinicians to question the biology of breast cancer.

"A lot of us have the preconceived notion that if you have N2 or N3 disease, [the] outcome is very bad. But in actuality, it may not be the case," he said. "You may have a subset [of patients] who do quite well, who are true stage III rather than stage IV."

Dr. Chu reported no conflicts.

HOT SPRINGS, VA. – An analysis of a prospectively collected database indicates that breast cancer patients with multiple nodal disease need a metastatic work-up only if they have tumor grade 3 or 4.

Current NCCN (National Comprehensive Cancer Network) guidelines recommend that patients with stage III and node-positive disease receive a work-up if they are N1. But the NCCN guidelines are less clear about what to do about N2 and N3 patients, said Dr. Quyen Chu at the annual meeting of the Southern Surgical Association.

About 20% of patients with stage III disease will have distant metastases, said Dr. Chu, chief of the surgical oncology division at Louisiana State University Health Sciences Center, Shreveport.

He and his colleagues at LSU extracted data from an ongoing, prospective breast cancer database, which was created in 1998 and comprises patient experience primarily from the LSU center but also from E.A. Conway Hospital in Monroe, La. They analyzed 256 patients with N2 or N3 disease who began treatment in 2010.

There was little difference between the two groups. The mean age of the 158 N2 patients was 58 years; it was 57 for the 68 N3 patients. The mean tumor grade was 2.5, and the mean tumor size was 4.6 cm. The tumor stage was similar between the two groups, with about 40% overall staged at T2.

"Are we risking an observation based on the play of chance?"

About half of the tumors were estrogen receptor positive overall. There was no difference in estrogen receptor status between the two groups. But more of the N3 patients had HER2-positive tumors, at 43% (31 of 72 patients), compared with 26% (27 of 103 patients) for the N2 group.

The primary end point for the study was the incidence of stage IV disease, either at the time of diagnosis or within 30 days of surgery. Patients underwent bone scans, CT, and/or PET to detect metastases.

Unexpectedly, the researchers found two T0 patients and 35 T1 patients who had stage III metastatic disease. The overall risk of stage IV disease was 16%. In all, 6% of T2 patients had stage IV disease, compared with 22% of T3 patients and 36% of T3 patients.

By N stage, about 83% of N2 and N3 patients had stage III disease, whereas 15% of each group had stage IV disease.

There was no difference in overall survival between the N2 and N3 groups, but those with stage IV disease had a predictably and statistically significant lower overall survival. Using a Cox proportional hazard model, the researchers determined that the only significant predictors of survival were T stage and grade.

Commenting on the paper, Dr. William C. Wood said that Dr. Chu’s observations were "unique," and that the data might help clinicians to more accurately judge tumor progression. "The rate of progression is very important to prognosis," said Dr. Wood, professor of surgery at Emory University in Atlanta. He cautioned, however, that the data set was small. Given that there was no difference in prognosis among the N2 and N3 groups, he asked, "Are we risking an observation based on the play of chance?"

Dr. Wood also suggested that there might not be any utility to identifying patients who had asymptomatic stage IV disease. Staging studies could be avoided, along with potential false positives, and the decision to not identify such patients "could avoid a longer period [of] awareness of stage IV disease in a person who could otherwise be blissfully unaware," he said.

Dr. Chu agreed that this was a valid question. But he suggested that newer agents and aggressive surgical intervention have been shown recently to potentially extend survival in stage IV disease.

Several other commentators wondered if the findings had prompted any change at LSU. "This paper by no means suggests we should change our standard of care," said Dr. Chu. It might prompt some review of the role of different imaging modalities used, he noted. And he added that the study should cause clinicians to question the biology of breast cancer.

"A lot of us have the preconceived notion that if you have N2 or N3 disease, [the] outcome is very bad. But in actuality, it may not be the case," he said. "You may have a subset [of patients] who do quite well, who are true stage III rather than stage IV."

Dr. Chu reported no conflicts.

SAN ANTONIO – A new meta-analysis challenges the notion that breast cancer risk is inversely related to serum vitamin D level.

The meta-analysis included 16 published studies deemed by investigators to have made the grade in terms of scientific rigor. In 10 studies, vitamin D was measured before diagnosis of breast cancer, while in the other 6 studies, blood samples were gathered for measurement of vitamin D only after the diagnosis.

When data from all 16 studies were pooled, lower vitamin D levels were associated with a significant 1.5-fold increased rate of breast cancer (P less than .001). So far so good for the theory that low vitamin D might be causally related to breast cancer, and by extension for the corollary that vitamin D supplementation might be an effective option for breast cancer prevention.

However, a major difficulty with this line of thinking arose when the two groups of studies were analyzed separately, Dr. Eitan Amir explained at the San Antonio Breast Cancer Symposium.

Indeed, only 1 of the 10 studies in which vitamin D was measured before diagnosis of breast cancer showed a significant relationship between low levels of vitamin D and subsequent increased likelihood of the malignancy.

In contrast, all six studies in which serum vitamin D was measured following diagnosis of breast cancer showed a significant inverse relationship. In the pooled analysis of these six studies, lower serum vitamin D was associated with a highly significant, 2.63-fold increased likelihood of breast cancer (P less than .001), according to Dr. Amir of the University of Toronto.

Breast cancer cells have been shown to express vitamin D catalytic enzymes that may interfere with accurate measurement of serum levels of the vitamin, added Dr. Amir.

Dr. Amir declared having no relevant financial interests.

SAN ANTONIO – A new meta-analysis challenges the notion that breast cancer risk is inversely related to serum vitamin D level.

The meta-analysis included 16 published studies deemed by investigators to have made the grade in terms of scientific rigor. In 10 studies, vitamin D was measured before diagnosis of breast cancer, while in the other 6 studies, blood samples were gathered for measurement of vitamin D only after the diagnosis.

When data from all 16 studies were pooled, lower vitamin D levels were associated with a significant 1.5-fold increased rate of breast cancer (P less than .001). So far so good for the theory that low vitamin D might be causally related to breast cancer, and by extension for the corollary that vitamin D supplementation might be an effective option for breast cancer prevention.

However, a major difficulty with this line of thinking arose when the two groups of studies were analyzed separately, Dr. Eitan Amir explained at the San Antonio Breast Cancer Symposium.

Indeed, only 1 of the 10 studies in which vitamin D was measured before diagnosis of breast cancer showed a significant relationship between low levels of vitamin D and subsequent increased likelihood of the malignancy.

In contrast, all six studies in which serum vitamin D was measured following diagnosis of breast cancer showed a significant inverse relationship. In the pooled analysis of these six studies, lower serum vitamin D was associated with a highly significant, 2.63-fold increased likelihood of breast cancer (P less than .001), according to Dr. Amir of the University of Toronto.

Breast cancer cells have been shown to express vitamin D catalytic enzymes that may interfere with accurate measurement of serum levels of the vitamin, added Dr. Amir.

Dr. Amir declared having no relevant financial interests.

SAN ANTONIO – A new meta-analysis challenges the notion that breast cancer risk is inversely related to serum vitamin D level.

The meta-analysis included 16 published studies deemed by investigators to have made the grade in terms of scientific rigor. In 10 studies, vitamin D was measured before diagnosis of breast cancer, while in the other 6 studies, blood samples were gathered for measurement of vitamin D only after the diagnosis.

When data from all 16 studies were pooled, lower vitamin D levels were associated with a significant 1.5-fold increased rate of breast cancer (P less than .001). So far so good for the theory that low vitamin D might be causally related to breast cancer, and by extension for the corollary that vitamin D supplementation might be an effective option for breast cancer prevention.

However, a major difficulty with this line of thinking arose when the two groups of studies were analyzed separately, Dr. Eitan Amir explained at the San Antonio Breast Cancer Symposium.

Indeed, only 1 of the 10 studies in which vitamin D was measured before diagnosis of breast cancer showed a significant relationship between low levels of vitamin D and subsequent increased likelihood of the malignancy.

In contrast, all six studies in which serum vitamin D was measured following diagnosis of breast cancer showed a significant inverse relationship. In the pooled analysis of these six studies, lower serum vitamin D was associated with a highly significant, 2.63-fold increased likelihood of breast cancer (P less than .001), according to Dr. Amir of the University of Toronto.

Breast cancer cells have been shown to express vitamin D catalytic enzymes that may interfere with accurate measurement of serum levels of the vitamin, added Dr. Amir.

Dr. Amir declared having no relevant financial interests.

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.

SAN ANTONIO – Acupuncture for the reduction of aromatase inhibitor–related musculoskeletal symptoms in breast cancer patients proved a disappointment in an interim analysis of a double-blind, randomized, sham-controlled, multicenter clinical trial.

Both real and sham acupuncture turned out to provide similar reductions in the Health Assessment Questionnaire Disability Index (HAQ-DI), the primary study end point. The two groups also experienced similar improvement in scores on a pain visual analog scale after eight weekly real or sham treatment sessions, Dr. Ting Bao reported at the San Antonio Breast Cancer Symposium.

©Liang Zhang/iStockphoto.com

The double-blind randomized trial included 47 postmenopausal women with early-stage breast cancer who were experiencing musculoskeletal symptoms related to aromatase inhibitor use. None of the patients had received acupuncture in the previous year.

The acupuncture group received eight weekly sessions targeting 15 acupuncture points. The control group got a sham acupuncture procedure at 14 non-acupuncture points. The sham therapy utilized the Park Sham Device, which consists of a nonpenetrating, retractable acupuncture needle and an adhesive tube. From a median baseline HAQ-DI score of 0.75, 8 of 23 patients in the real acupuncture group achieved the minimum clinically important improvement, predefined as a 0.22-point reduction. So did 13 of 24 women in the sham acupuncture group.

Pain scores on a visual analog scale improved to a similar extent in the two study arms, from a baseline median of 50 out of a possible 100 to 41 in the real acupuncture group and 36 in the sham group.

When the blinded patients were asked to guess their treatment assignment, 55% in each group did so accurately, according to Dr. Bao, a medical oncologist and licensed acupuncturist at the University of Maryland Greenebaum Cancer Center, Baltimore.

Plasma estradiol levels remained undetectable in most patients during the study period.

No significant side effects were noted in either study arm.

About half of breast cancer patients on adjuvant aromatase inhibitor therapy experience musculoskeletal symptoms. These side effects can be sufficiently debilitating as to lead to poor compliance or even treatment discontinuation.

Among the possible explanations for the negative results in this study are that the HAQ-DI may not be a sufficiently sensitive tool to detect small differences in effectiveness between real and sham acupuncture, and that sham acupuncture may not be an inert procedure, Dr. Bao said.

Although this randomized trial originally was scheduled to enroll 100 patients, it was halted early for futility based on the interim results.

The study was funded by a Komen grant and an ASCO Young Investigator Award. Dr. Bao declared having no financial conflicts.

SAN ANTONIO – Acupuncture for the reduction of aromatase inhibitor–related musculoskeletal symptoms in breast cancer patients proved a disappointment in an interim analysis of a double-blind, randomized, sham-controlled, multicenter clinical trial.

Both real and sham acupuncture turned out to provide similar reductions in the Health Assessment Questionnaire Disability Index (HAQ-DI), the primary study end point. The two groups also experienced similar improvement in scores on a pain visual analog scale after eight weekly real or sham treatment sessions, Dr. Ting Bao reported at the San Antonio Breast Cancer Symposium.

©Liang Zhang/iStockphoto.com

The double-blind randomized trial included 47 postmenopausal women with early-stage breast cancer who were experiencing musculoskeletal symptoms related to aromatase inhibitor use. None of the patients had received acupuncture in the previous year.

The acupuncture group received eight weekly sessions targeting 15 acupuncture points. The control group got a sham acupuncture procedure at 14 non-acupuncture points. The sham therapy utilized the Park Sham Device, which consists of a nonpenetrating, retractable acupuncture needle and an adhesive tube. From a median baseline HAQ-DI score of 0.75, 8 of 23 patients in the real acupuncture group achieved the minimum clinically important improvement, predefined as a 0.22-point reduction. So did 13 of 24 women in the sham acupuncture group.

Pain scores on a visual analog scale improved to a similar extent in the two study arms, from a baseline median of 50 out of a possible 100 to 41 in the real acupuncture group and 36 in the sham group.

When the blinded patients were asked to guess their treatment assignment, 55% in each group did so accurately, according to Dr. Bao, a medical oncologist and licensed acupuncturist at the University of Maryland Greenebaum Cancer Center, Baltimore.

Plasma estradiol levels remained undetectable in most patients during the study period.

No significant side effects were noted in either study arm.

About half of breast cancer patients on adjuvant aromatase inhibitor therapy experience musculoskeletal symptoms. These side effects can be sufficiently debilitating as to lead to poor compliance or even treatment discontinuation.

Among the possible explanations for the negative results in this study are that the HAQ-DI may not be a sufficiently sensitive tool to detect small differences in effectiveness between real and sham acupuncture, and that sham acupuncture may not be an inert procedure, Dr. Bao said.

Although this randomized trial originally was scheduled to enroll 100 patients, it was halted early for futility based on the interim results.

The study was funded by a Komen grant and an ASCO Young Investigator Award. Dr. Bao declared having no financial conflicts.

SAN ANTONIO – Acupuncture for the reduction of aromatase inhibitor–related musculoskeletal symptoms in breast cancer patients proved a disappointment in an interim analysis of a double-blind, randomized, sham-controlled, multicenter clinical trial.

Both real and sham acupuncture turned out to provide similar reductions in the Health Assessment Questionnaire Disability Index (HAQ-DI), the primary study end point. The two groups also experienced similar improvement in scores on a pain visual analog scale after eight weekly real or sham treatment sessions, Dr. Ting Bao reported at the San Antonio Breast Cancer Symposium.

©Liang Zhang/iStockphoto.com

The double-blind randomized trial included 47 postmenopausal women with early-stage breast cancer who were experiencing musculoskeletal symptoms related to aromatase inhibitor use. None of the patients had received acupuncture in the previous year.

The acupuncture group received eight weekly sessions targeting 15 acupuncture points. The control group got a sham acupuncture procedure at 14 non-acupuncture points. The sham therapy utilized the Park Sham Device, which consists of a nonpenetrating, retractable acupuncture needle and an adhesive tube. From a median baseline HAQ-DI score of 0.75, 8 of 23 patients in the real acupuncture group achieved the minimum clinically important improvement, predefined as a 0.22-point reduction. So did 13 of 24 women in the sham acupuncture group.

Pain scores on a visual analog scale improved to a similar extent in the two study arms, from a baseline median of 50 out of a possible 100 to 41 in the real acupuncture group and 36 in the sham group.

When the blinded patients were asked to guess their treatment assignment, 55% in each group did so accurately, according to Dr. Bao, a medical oncologist and licensed acupuncturist at the University of Maryland Greenebaum Cancer Center, Baltimore.

Plasma estradiol levels remained undetectable in most patients during the study period.

No significant side effects were noted in either study arm.

About half of breast cancer patients on adjuvant aromatase inhibitor therapy experience musculoskeletal symptoms. These side effects can be sufficiently debilitating as to lead to poor compliance or even treatment discontinuation.

Among the possible explanations for the negative results in this study are that the HAQ-DI may not be a sufficiently sensitive tool to detect small differences in effectiveness between real and sham acupuncture, and that sham acupuncture may not be an inert procedure, Dr. Bao said.

Although this randomized trial originally was scheduled to enroll 100 patients, it was halted early for futility based on the interim results.

The study was funded by a Komen grant and an ASCO Young Investigator Award. Dr. Bao declared having no financial conflicts.