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

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.

Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer

“…Patient prognosis is determined largely by stratification based on age, lymph node involvement, tumor grade, and tumor cell-surface expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) (2)(3)(4)(5)(6)(7). Early diagnosis and targeted therapies, both hormonal and immunologic, are critical for the effective treatment of ER-, PR-, and HER2-positive disease.…”

Androgen receptor expression in triple negative breast cancer and its relationship to prognostic factors

“…Considering that the main treatment of TNBC 29 is chemotherapy, in vitro studies show that AR activation can reduce chemotherapy efficacy in LAR subtype through the AR-mediated transcriptional regulation of pro-and anti-apoptotic genes, suggesting the usefulness of an AR block combined with chemotherapy in this setting 30 . The present study has some limitations that should be noted.…”

Combination Treatment of Polo-Like Kinase 1 and Tankyrase-1 Inhibitors Enhances Anticancer Effect in Triple-negative Breast Cancer Cells

“…Over half of patients with BRCAmutated, metastatic breast cancer have tumors classified as triple-negative, and clinical trials to assess the efficacy and safety of a TNKS inhibitor in metastatic TNBC patients are currently being conducted (32,33). TNKS1 was first identified as a TRF-binding protein and a member of the PARP family (34).…”