Triple positive breast cancer: A distinct subtype?

Patrizia Vici, Laura Pizzuti, Clara Natoli, Teresa Gamucci, Luigi Di Lauro, Maddalena Barba, Domenico Sergi, Claudio Botti, Andrea Michelotti, Luca Moscetti, Luciano Mariani, Fiorentino Izzo, Loretta D'Onofrio, Isabella Sperduti, Francesca Conti, Valentina Rossi, Alessandra Cassano, Marcello Maugeri-Saccà, Marcella Mottolese, Paolo Marchetti

Research output: Contribution to journalArticlepeer-review

Abstract

Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decreased overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct subtypes, with dissimilar clinical behavior and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the "standard" treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalCancer Treatment Reviews
Volume41
Issue number2
DOIs
Publication statusPublished - Feb 1 2015

Keywords

  • Anti-HER-2 agents
  • Breast cancer
  • Chemotherapy
  • Hormonal therapy
  • Triple positive

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

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