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Oncotarget. 2016 Apr 5;7(14):17932-44. doi: 10.18632/oncotarget.7480.

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

Author information

  • 1Division of Medical Oncology 2, "Regina Elena" National Cancer Institute, Rome, Italy.
  • 2Biostatistics Unit, "Regina Elena" National Cancer Institute, Rome, Italy.
  • 3Division of Oncology, S. Anna Hospital, Ferrara, Italy.
  • 4Department of Experimental and Clinical Sciences, University "G. d'Annunzio", Chieti, Italy.
  • 5Medical Oncology Unit, ASL Frosinone, Frosinone, Italy.
  • 6Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Oncology Unit, Istituto Chirurgico Ortopedico Traumatologico, Latina, Italy.
  • 7Oncology Unit I, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
  • 8Department of Oncology, Division of Medical Oncology, Belcolle Hospital, ASL Viterbo, Viterbo, Italy.
  • 9Department of Oncology, Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy.
  • 10Department of Medical Oncology, S. Luca Hospital, Lucca, Italy.
  • 11Division of Medical Oncology, IRCCS, Giovanni Paolo II Hospital, Bari, Italy.
  • 12Medical Oncology, Catholic University of Sacred Heart, Rome, Italy.
  • 13Department of Medical Oncology, University Campus Bio-Medico, Rome, Italy.
  • 14Medical Oncology, Ospedale San Giovanni Calibita Fatebenefratelli, Rome, Italy.
  • 15Oncology Unit, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy.
  • 16Medical Oncology, S. Spirito Hospital, Rome, Italy.
  • 17Scientific Direction, "Regina Elena" National Cancer Institute, Rome, Italy.
  • 18Department of Molecular Medicine, "Umberto I", "Sapienza" University of Rome, Roma, Italy.
  • 19Investigative Clinical Oncology, Fondazione del Piemonte per l'Oncologia-Candiolo Cancer Institute (IRCCs), Candiolo, Italy.
  • 20Division of Medical Oncology, Ospedale Civile di Saluzzo, Saluzzo, Italy.


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.


adjuvant breast cancer; chemotherapy; hormonal receptors; trastuzumab; triple positive

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