Triple-negative Breast Cancer: Disease Entity or Title of Convenience?

Lisa Carey; Eric Winer; Giuseppe Viale; David Cameron; Luca Gianni

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In This Article

Abstract and Introduction

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.

Introduction

In April 2009, the Fondazione Michelangelo and the Fondazione IRCCS Istituto Nazionale dei Tumori organized the ninth in a series of seminars on recent advances and controversies in breast cancer. This seminar was designed to update practicing clinicians on 'triple-negative' breast cancer (TNBC)—that is the subgroup of tumors that do not express clinically significant levels of the estrogen receptor (ER), progesterone receptor (PgR) and HER2. In particular, the seminar addressed the question of whether TNBC is a distinct pathological subtype of breast cancer or a pragmatic category for determining eligibility for clinical trials and guiding individual patient treatment. In addition, emerging treatment strategies were discussed because patients with TNBC are not eligible for hormonal therapies or HER2-targeted agents and, therefore, have no established systemic therapy options other than chemotherapy.

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