From the Fellow, Breast Cancer Medicine Service, Assistant Attending, Breast Cancer Medicine Service, Attending Physician and Chief, Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
Authors disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Clifford A. Hudis, MD, Attending Physician and Chief, Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, 1114 1st Avenue, New York, NY 10065; email: hudisc{at}mskcc.org
Overview: The anthracyclines, doxorubicin and epirubicin, are among the most active agents in breast cancer. In the adjuvant setting, anthracycline-based chemotherapy regimens are associated with a 4.2% increase in survival compared with conventional non-anthracycline–based regimens and a low risk of congestive heart failure (CHF). Historically, adjuvant chemotherapy recommendations were based on patient and tumor characteristics such as age, comorbid conditions, tumor size, node status, and hormone receptor status. These recommendations are now increasingly tailored to specific molecular profiles, most notably the human epidermal growth factor receptor 2 (HER-2) -status. In the pivotal phase III adjuvant trials, for example, the combination of chemotherapy with trastuzumab resulted in significant survival benefits for the 20% to 30% of patients with HER-2-positive breast cancer compared with chemotherapy alone. However, as investigators strive to optimize therapeutic recommendations, significant controversy has emerged regarding the role of topoisomerase II-alpha amplification and anthracycline activity in patients with HER-2-positive breast cancer. Most patients, however, have HER-2-normal breast cancer. For patients with high risk HER-2-normal breast cancer, sequential anthracycline-taxane regimens have demonstrated superior outcomes compared with non-anthracycline–based regimens in both younger and, recently, in older populations. Many of these regimens have been further refined through therapeutic innovation, such as dose-dense administration which improves survival without increasing the risk of CHF. However, optimizing therapeutic recommendations for patients with lower-risk diseases remains a clinical challenge. This challenge has been addressed, in part, by the recent development of several risk-benefit calculation tools, including a computer-based program, and several gene expression profiling tools. These have not, however, been used to select patients for anthracycline use, and thus, these agents remain an important option for most patients considering adjuvant chemotherapy.