"Triple positive" early breast cancer: An observational multicenter retrospective analysis of outcome

Alessandra Cassano, Ruggero De Maria Marchiano, Teresa Gamucci, Paolo Marchetti, Patrizia Vici, Laura Pizzuti, Isabella Sperduti, Antonio Frassoldati, Clara Natoli, Silverio Tomao, Andrea Michelotti, Luca Moscetti, Stefania Gori, Editta Baldini, Francesco Giotta, Daniele Santini, Diana Giannarelli, Luigi Di Lauro, Domenico Cristiano Corsi, Valentina SiniDomenico Sergi, Maddalena Barba, Marcello Maugeri-Saccà, Michelangelo Russillo, Lucia Mentuccia, Loretta D'Onofrio, Laura Iezzi, Angelo Fedele Scinto, Lucia Da Ros, Ilaria Bertolini, Maria Luisa Basile, Valentina Rossi, Filippo Montemurro

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24 Citations (Scopus)

Abstract

We recently found that trastuzumab benefit may be lower in a small subset of early breast cancer (BC) patients (pts) with tumors expressing high levels of both hormonal receptors (HRs), i.e. triple positive (TP). To better investigate the role of HRs in HER2 positive BC, we retrospectively identified 872 TP BC pts treated with adjuvant chemotherapy alone (cohort A-366 pts), or plus trastuzumab (cohort B-506 pts). Relapse-free-survival (RFS) and breast-cancer-specific-survival (BCSS) were evaluated. Trastuzumab improved RFS and BCSS in all the subsets analyzed, but the effect on BCSS in tumors expressing both HRs in >30% of cells (TP30), and even on RFS in tumors with both HRs expressed in >50% of cells (TP50) was not significant. Distinct patterns of relapse were observed in TP50 and no-TP50 tumors, the former showing low and constant risk in the first 5 years, a late increase beyond 5 years and modest trastuzumab effect. Trastuzumab effect tended to disappear in pts whose tumors expressed ER in >50% of cells. Multivariate analysis of RFS confirmed a significant interaction between trastuzumab and ER expression, with benefit confined to pts whose tumors expressed ER in ≤50% of cells. Our data suggest that the pattern of relapse of TP tumors with high HRs is similar to that of "luminal", HER2 negative tumors, without clear benefit from adjuvant trastuzumab, which remains the standard treatment even in TP tumors. Confirmatory findings on the extent to which quantitative expression of HRs may impact clinical behavior of HER2 positive BC are warranted.
Original languageEnglish
Pages (from-to)17932-17944
Number of pages13
JournalOncotarget
Volume7
DOIs
Publication statusPublished - 2016

Keywords

  • Adjuvant breast cancer
  • Chemotherapy
  • Hormonal receptors
  • Oncology
  • Trastuzumab
  • Triple positive

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