Triple-negative breast cancer: advancements in characterization and treatment approach.

Abstract

Triple-negative breast cancer (TNBC) comprises 15-20% of all breast cancer and is defined by the lack of estrogen and progesterone receptor expression and absence of human epidermal growth factor receptor 2 amplification. Compared with patients with hormone receptor positive or Her-2 positive breast cancer, patients with TNBC are more commonly young (age <50 years), African-American and have a higher incidence of BRCA1/2 mutations. The clinical course is frequently characterized by early relapse and poor overall survival. The TNBC phenotype is impervious to therapies commonly used in other breast cancer subtypes, including hormonal therapy and Her-2 receptor antagonism. Cytotoxic chemotherapy remains the only approved treatment. With its aggressive clinical course and paucity of effective treatment options, TNBC represents an unmet clinical need. This review will focus on updates of the biologic underpinnings of TNBC and the associated treatment advances. Numerous advancements have been made toward understanding the biologic framework of TNBC. Gene expression profiling has revealed six clinically relevant subsets of TNBC. Further study has demonstrated a portion of TNBC exhibits a strong immune gene signature. Lastly, it is now appreciated that a subgroup of sporadic TNBC shares biologic characteristics with BRCA1/2-mutated breast cancer, notably homologous repair deficiency. Recent studies focus on incorporation of platinum salts and new combinations of conventional chemotherapeutic agents. Targeted agents, including poly-ADP ribose polymerase inhibitors, antiangiogenic agents, phosphoinositide 3-kinase (PI3K) pathway inhibitors, and androgen antagonist are also being evaluated. Most recently, checkpoint inhibitors have demonstrated a modest degree of activity in a subset of TNBC. These discoveries are informing novel treatment paradigms and identification of correlative biomarkers in TNBC. Improved understanding of the biologic heterogeneity of TNBC is allowing for a more effective and individualized approach to treatment.