With 246,660 new diagnoses and 40,450 deaths projected for 2016, breast cancer remains the most commonly diagnosed and the second leading cause of cancer-related deaths among women in USA.1Although most patients will be diagnosed with localized breast cancer, ~6% of patients will present with de novo metastatic disease and ~10%–40% of patients with localized breast cancer will relapse systemically (as opposed to locally).2,3 The prognosis of patients with metastatic breast cancer (mBC) is heterogeneous and can range from several months to many years depending upon many factors, including, but not limited to, estrogen and progesterone receptor (ER/PR) status and human epidermal growth factor receptor 2 (HER2) receptor status.2,3 Metastatic tumors that are ER/PR negative and HER2 negative are characterized as being triple negative and, although not considered synonymous, are generally thought to consist of tumors, which harbor a basal-like molecular subtype (Figure 1). Most new treatment options for mBC recently approved by the Food and Drug Administration (FDA) are only effective for ER/PR-positive or HER2-positive metastatic tumors, and relatively few new agents have been approved for the subset of patients with metastatic triple-negative breast cancer (mTNBC). Single-agent chemotherapy continues to serve as the backbone of mBC treatment. The lack of efficacious therapy within this cohort, combined with the propensity to develop visceral or central nervous system (CNS) metastasis (as opposed to more indolent bone or soft tissue predominant metastases), has translated into an overall survival (OS) that has remained stagnant over the past 20 years.4–6 As a result, patients with mTNBC continue to have a considerably worse OS when compared to their mBC counterparts. The purpose of this review is to perform a comprehensive evaluation of the principles of systemic treatment, compare standard systemic palliative options, and highlight the promising approaches in ongoing clinical trials in mTNBC.

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(To view a larger version of Figure 1, click here.)


Although mTNBC encompasses a unique subset of patients, the therapeutic approach mimics that of other subsets of patients with mBC (Figure 2). As opposed to patients with localized breast cancer where the primary goal of treatment is cure, treatment of mBC focuses on prolonging the progression-free survival (PFS) and OS and improving the quality of life (QOL) through the reduction or stabilization of tumor burden and other cancer-related symptoms.7–9 Due to the palliative intent, it is critical that an individualized approach is taken that incorporates patient, disease, and treatment-related factors, including an individual oncologist treatment preference.

(To view a larger version of Figure 2, click here.)