Triple-negative breast cancer: disease entity or title of convenience?

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Abstract

This Review outlines the understanding and management of triple-negative breast cancer (TNBC). TNBC shares morphological and genetic abnormalities with basal-like breast cancer (BLBC), a subgroup of breast cancer defined by gene-expression profiling. However, TNBC and BLBC tumors are heterogeneous and overlap is incomplete. Breast cancers found in BRCA1 mutation carriers are also frequently triple negative and basal like. TNBC and BLBC occur most frequently in young women, especially African Americans, and tend to exhibit aggressive, metastatic behavior. These tumors respond to conventional chemotherapy but relapse more frequently than hormone receptor-positive, luminal subtypes and have a worse prognosis. New systemic therapies are urgently needed as most patients with TNBC and/or BLBC relapse with distant metastases, and hormonal therapies and HER2-targeted agents are ineffective in this group of tumors. Poly (ADP-ribose) polymerase inhibitors, angiogenesis inhibitors, EGFR-targeted agents, and src kinase and mTOR inhibitors are among the therapeutic agents being actively investigated in clinical trials in patients with TNBC and/or BRCA1-associated tumors. Increased understanding of the genetic abnormalities involved in the pathogenesis of TNBC, BLBC and BRCA1-associated tumors is opening up new therapeutic possibilities for these hard-to-treat breast cancers.

Key Points

  • Triple-negative breast cancer (TNBC), a subgroup that lacks expression of hormone receptors and HER2, overlaps with basal-like breast cancer (BLBC), a subgroup that expresses cytokeratins and other non-luminal (basal) genes

  • Breast cancers occurring in patients with germline BRCA1 mutations are often triple negative and basal like, and BRCA1 defects or deficiency may be involved in sporadic TNBC and BLBC

  • Although heterogeneous, TNBCs and BLBCs typically occur in younger women, and are associated with a range of adverse biological features including high grade, high mitotic count and p53 positivity

  • Although responsive to chemotherapy, TNBCs and BLBCs tend to relapse and metastasize early and have a worse prognosis than other tumor subtypes

  • There are no specific therapies for patients with TNBC or BLBC; new treatments under investigation include novel cytotoxics, poly (ADP-ribose) polymerase inhibitors, angiogenesis inhibitors, EGFR-targeted agents, and src kinase inhibitors

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Figure 1: Shared features of triple-negative, basal-like and BRCA1-associated breast cancers.

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Acknowledgements

We would like to thank C. Barton (consultant of Fondazione Michelangelo, the non-profit organization that organized the seminar on TNBC) for assistance in preparing the manuscript.

Author information

All authors researched the data for the article and provided a substantial contribution to discussions of the content. L. Carey wrote the article and all authors contributed to the review and/or editing of the manuscript before submission.

Correspondence to Luca Gianni.

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Competing interests

E. Winer has received grants or research support from Genentech. D. Cameron acts as a consultant for and has received research support from Pfizer and Roche and is a consultant for Sanofi-Aventis. L. Gianni acts as a consultant for Biogen Idec, Eisai, Genentech, GlaxoSmithKline, Millennium Pharmaceuticals, Novartis, Roche and Sanofi-Aventis. L. Carey and G. Viale declare no competing interests.

Supplementary information

Supplementary Table 1

Ongoing randomized trials of treatment in TNBC, BLBC and/or BRCA1 breast cancer (DOC 84 kb)

Supplementary Table 2

Ongoing trials of PARP inhibitors in TNBC, BLBC and/or BRCA1 breast cancer (DOC 93 kb)

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