Systemic treatment strategies for triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2 (EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubMed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival (PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitors in combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success.

Keywords: Breast cancer, Triple negative, Basal like, BRCA1, Poly (ADP-ribose) polymerase 1, Targeted therapy, Chemotherapy

Core tip: Breast cancer is a heterogeneous disease entity with different biological characteristics and clinical behavior. There are no treatment guidelines for triple-negative breast cancer (TNBC). TNBCs are sensitive to taxanes and anthracyclins but there are high rates of local and systemic relapses. Recently there has been great interest in platinum agents, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have shown improved response rates (RRs). Other useful drugs are antiangiogenic agents, tyrosine kinase and epidermal growth factor receptor inhibitors with variable RRs but no survival benefit. In this review, we discuss various systemic treatment strategies available for TNBC and the benefit from each of them.