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Triple-negative breast cancer: molecular subtypes and targeted therapy

Hirshfield, Kim M.; Ganesan, Shridar

Current Opinion in Obstetrics and Gynecology: February 2014 - Volume 26 - Issue 1 - p 34–40
doi: 10.1097/GCO.0000000000000038
BREAST CANCER: Edited by Gottfried E. Konecny

Purpose of review Triple-negative breast cancers (TNBCs), lacking estrogen receptor expression and human epidermal growth factor receptor 2 amplification, have no effective targeted therapy. Large-scale comprehensive genomic analyses have allowed stratification of TNBCs by molecular features. We will review the recent data regarding the classification of these poor prognosis cancers and the associated potential targeted treatment approaches.

Recent findings TNBCs are a heterogeneous set of cancers characterized by a diverse set of gene-expression patterns and underlying genomic changes. Mutations in p53 are the only genomic alteration present in the majority of TNBCs. Other potential targetable alterations are only present in small subsets of TNBCs, and include defects in DNA repair present in BRCA1-mutant TNBCs and some sporadic TNBCs. Antiandrogens may be effective for TNBCs that express the androgen receptor and have luminal-like gene-expression features. PI3KCA pathway inhibitors and HSP90 inhibitors may also be effective in a small fraction of TNBCs.

Summary Robust methods to functionally classify TNBCs to determine vulnerable pathways are urgently needed to guide the development of clinical trials. It is quite possible that TNBCs, like non-small cell lung cancer, will be stratified into many individually rare cancer classes, each requiring a distinct treatment approach.

Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey, USA

Correspondence to Shridar Ganesan, MD, PhD, Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA. Tel: +1 732 235 5211; e-mail:

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins