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Breast-Cancer Therapy — Looking Back to the Future
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BREAST-CANCER THERAPY — LOOKING BACK TO THE FUTURE* Anne Moore, MD
ADJUVANT therapy for breast cancer-treatment after surgical removal of the tumor-is a major therapeutic advance that has had a considerable effect on prolonging disease-free and overall survival. Not all patients benefit from adjuvant therapy, however, and certain types of adjuvant therapy are not appropriate for some patients. For example, adjuvant treatment with tamoxifen, a selective estrogen-receptor modulator, has improved the 15-year survival rate among women with estrogen-receptor–positive breast cancer by 31%, but it does not benefit women with estrogenreceptor-negative disease. Trastuzumab, a monoclonal antibody against the human epidermal growth factor receptor type 2 (HER2), is associated with an improvement of approximately 50% in disease-free survival among the 15 to 20% of women with HER2-positive disease. In addition to these targeted approaches, adjuvant chemotherapy that includes alkylating agents, antimetabolites, anthracyclines, and taxanes in various combinations has contributed to the overall improvement in outcomes among women with operable breast cancer. As compared with women with estrogen-receptor–positive disease, women with estrogen-receptor–negative breast cancer benefit more from chemotherapy. A recent retrospective analysis of three trials by the Cancer and Leukemia Group B (CALGB) suggests very little overall benefit of adjuvant chemotherapy for women with estrogen-receptor–positive breast cancer who received tamoxifen for 5 years after receiving chemotherapy. Why should we spare our patients from paclitaxel? The toxicity profile of this drug is unique. Hypersensitivity reactions (including, rarely, anaphylaxis) occur during the infusion of paclitaxel, despite premedication with
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corticosteroids. Such reactions were reported in 6% of patients in the CALGB 9344 trial. A transient symptom complex of myalgia, arthralgia, and neuralgia is common within 2 to 3 days after the infusion. Neurotoxicity, the predominant side effect, was reported in 18% of patients in the CALGB 9344 trial. For some patients, numbness and tingling in the hands and feet last for months or even years after treatment is completed. Thirteen years have passed since the first patient was enrolled in the CALGB 9344 trial. During this time, important changes in practice may have diminished the value of adding paclitaxel to chemotherapy for women with HER2-negative, estrogen-receptor–positive breast cancer. For instance, advances in adjuvant endocrine therapy reduce the proportional benefit of adjuvant chemotherapy for women with estrogen-receptor– positive breast cancer. In postmenopausal women, the incorporation of an aromatase inhibitor (anastrozole, exemestane, or letrozole) into adjuvant therapy prolongs disease-free survival more than does treatment with tamoxifen for 5 years. Leaders of clinical trials should continue to look backward, when appropriate, for data such as those presented by Hayes et al. In looking to the future, correlative science must be incorporated into modern clinical trials in breast cancer. The days of “one size fits all” therapy for patients with breast cancer are coming to an end. *SOURCE INFORMATION: New England Journal of Medicine, Volume 357:1547-1549 October 11, 2007 . From the Division of Hematology–Oncology, Weill Cornell Medical College, Cornell University Medical Center, New York.
Apollo Medicine, Vol. 5, No. 3, September 2008
BREAST-CANCER THERAPY — LOOKING BACK TO THE FUTURE* Anne Moore, MD
ADJUVANT therapy for breast cancer-treatment after surgical removal of the tumor-is a major therapeutic advance that has had a considerable effect on prolonging disease-free and overall survival. Not all patients benefit from adjuvant therapy, however, and certain types of adjuvant therapy are not appropriate for some patients. For example, adjuvant treatment with tamoxifen, a selective estrogen-receptor modulator, has improved the 15-year survival rate among women with estrogen-receptor–positive breast cancer by 31%, but it does not benefit women with estrogenreceptor-negative disease. Trastuzumab, a monoclonal antibody against the human epidermal growth factor receptor type 2 (HER2), is associated with an improvement of approximately 50% in disease-free survival among the 15 to 20% of women with HER2-positive disease. In addition to these targeted approaches, adjuvant chemotherapy that includes alkylating agents, antimetabolites, anthracyclines, and taxanes in various combinations has contributed to the overall improvement in outcomes among women with operable breast cancer. As compared with women with estrogen-receptor–positive disease, women with estrogen-receptor–negative breast cancer benefit more from chemotherapy. A recent retrospective analysis of three trials by the Cancer and Leukemia Group B (CALGB) suggests very little overall benefit of adjuvant chemotherapy for women with estrogen-receptor–positive breast cancer who received tamoxifen for 5 years after receiving chemotherapy. Why should we spare our patients from paclitaxel? The toxicity profile of this drug is unique. Hypersensitivity reactions (including, rarely, anaphylaxis) occur during the infusion of paclitaxel, despite premedication with
257
corticosteroids. Such reactions were reported in 6% of patients in the CALGB 9344 trial. A transient symptom complex of myalgia, arthralgia, and neuralgia is common within 2 to 3 days after the infusion. Neurotoxicity, the predominant side effect, was reported in 18% of patients in the CALGB 9344 trial. For some patients, numbness and tingling in the hands and feet last for months or even years after treatment is completed. Thirteen years have passed since the first patient was enrolled in the CALGB 9344 trial. During this time, important changes in practice may have diminished the value of adding paclitaxel to chemotherapy for women with HER2-negative, estrogen-receptor–positive breast cancer. For instance, advances in adjuvant endocrine therapy reduce the proportional benefit of adjuvant chemotherapy for women with estrogen-receptor– positive breast cancer. In postmenopausal women, the incorporation of an aromatase inhibitor (anastrozole, exemestane, or letrozole) into adjuvant therapy prolongs disease-free survival more than does treatment with tamoxifen for 5 years. Leaders of clinical trials should continue to look backward, when appropriate, for data such as those presented by Hayes et al. In looking to the future, correlative science must be incorporated into modern clinical trials in breast cancer. The days of “one size fits all” therapy for patients with breast cancer are coming to an end. *SOURCE INFORMATION: New England Journal of Medicine, Volume 357:1547-1549 October 11, 2007 . From the Division of Hematology–Oncology, Weill Cornell Medical College, Cornell University Medical Center, New York.
Apollo Medicine, Vol. 5, No. 3, September 2008