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17-05-2016 | Triple-negative breast cancer | Article

Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease

Authors:
Giampaolo Bianchini, Justin M. Balko, Ingrid A. Mayer, Melinda E. Sanders, Luca Gianni

Abstract

Chemotherapy is the primary established systemic treatment for patients with triple-negative breast cancer (TNBC) in both the early and advanced-stages of the disease. The lack of targeted therapies and the poor prognosis of patients with TNBC have fostered a major effort to discover actionable molecular targets to treat patients with these tumours. Massively parallel sequencing and other 'omics' technologies have revealed an unexpected level of heterogeneity of TNBCs and have led to the identification of potentially actionable molecular features in some TNBCs, such as germline BRCA1/2 mutations or 'BRCAness', the presence of the androgen receptor, and several rare genomic alterations. Whether these alterations are molecular 'drivers', however, has not been clearly established. A subgroup of TNBCs shows a high degree of tumour-infiltrating lymphocytes that also correlates with a lower risk of disease relapse and a higher likelihood of benefit from chemotherapy. Proof-of-principle studies with immune-checkpoint inhibitors in advanced-stage TNBC have yielded promising results, indicating the potential benefit of immunotherapy for patients with TNBC. In this Review, we discuss the most relevant molecular findings in TNBC from the past decade and the most promising therapeutic opportunities derived from these data.

Nat Rev Clin Oncol 2016;13: 674-690. doi:10.1038/nrclinonc.2016.66

Subject terms: Breast cancer • Cancer immunotherapy • Chemotherapy • Targeted therapies • Tumour biomarkers

The clinical and molecular heterogeneity of breast cancer is well known. The advancement and widespread application of 'omics' technologies (genomics, epigenomics, transcriptomics or proteomics, among others) has provided unprecedented insights and novel understanding of the molecular complexity of this disease1, 2, 3, 4, 5. In spite of this complexity, clinical decisions still rely primarily on the assessment of three markers: the expression of the endocrine receptors for oestrogen and progesterone (ER and PgR, respectively) and the aberrant expression of HER2. The definition of triple-negative breast cancer (TNBC) applies to all tumours that lack the expression of ER, PgR and HER2, all of which are molecular targets of therapeutic agents. Nevertheless, chemotherapy is still the primary established treatment option for patients with early-stage and those with advanced-stage TNBC6.

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