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Metastatic breast cancer is a heterogeneous disease, and treatment decisions depend on several individualized patient and tumor characteristics. Although combination therapy often shows improved response rates in metastatic breast cancer, few studies have shown superiority in overall survival. The choice of combination versus sequential single-agent treatment, therefore, must consider many factors, with no one strategy right for all patients. This article reviews several important clinical trials that address this issue, and argues for single-agent sequential therapy for most patients with metastatic breast cancer.

Unlike estrogen receptor (ER)–positive and HER2-positive breast cancer, triple-negative breast cancer (TNBC) lacks a repertoire of targeted therapies. Hence, chemotherapy is the only available systemic option in current clinical practice. In general, survival of patients with TNBC is worse than that for those with ER-positive and HER2-positive breast cancer, especially for advanced-stage disease. Thus, a great unmet need exists. Conventional chemotherapeutic agents such as platinum-salts have been examined for specific benefit in TNBC; however, no one agent has yet been shown to offer a differential incremental benefit in metastatic TNBC. The hope is that ongoing research in targetable molecular pathways will lead to new therapeutic options for TNBC. Because these patients are likely to be increasingly subcategorized using potentially targetable molecular alterations, investigators will need to be mindful of the challenges in designing and conducting clinical trials in smaller subpopulations. The successful incorporation of targeted therapies in routine clinical practice for TNBC, which mirrors the success achieved by anti-HER2 and endocrine therapies, is awaited.