“Triple positive” early breast cancer: an observational multicenter retrospective analysis of outcome

// Patrizia Vici 1 , Laura Pizzuti 1 , Isabella Sperduti 2 , Antonio Frassoldati 3 , Clara Natoli 4 , Teresa Gamucci 5 , Silverio Tomao 6 , Andrea Michelotti 7 , Luca Moscetti 8 , Stefania Gori 9 , Editta Baldini 10 , Francesco Giotta 11 , Alessandra Cassano 12 , Daniele Santini 13 , Diana Giannarelli 2 , Luigi Di Lauro 1 , Domenico Cristiano Corsi 14 , Paolo Marchetti 15 , Valentina Sini 15, 16 , Domenico Sergi 1 , Maddalena Barba 1, 17 , Marcello Maugeri-Saccà 1, 17 , Michelangelo Russillo 10 , Lucia Mentuccia 5 , Loretta D’Onofrio 13 , Laura Iezzi 4 , Angelo Fedele Scinto 14 , Lucia Da Ros 3 , Ilaria Bertolini 7 , Maria Luisa Basile 18 , Valentina Rossi 19, 20 , Ruggero De Maria 17 , Filippo Montemurro 19 1 Division of Medical Oncology 2, “Regina Elena” National Cancer Institute, Rome, Italy 2 Biostatistics Unit, “Regina Elena” National Cancer Institute, Rome, Italy 3 Division of Oncology, S. Anna Hospital, Ferrara, Italy 4 Department of Experimental and Clinical Sciences, University “G. d’Annunzio”, Chieti, Italy 5 Medical Oncology Unit ASL Frosinone, Frosinone, Italy 6 Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Oncology Unit, Istituto Chirurgico Ortopedico Traumatologico, Latina, Italy 7 Oncology Unit I, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy 8 Department of Oncology, Division of Medical Oncology, Belcolle Hospital, ASL Viterbo, Viterbo, Italy 9 Department of Oncology, Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy 10 Department of Medical Oncology, S. Luca Hospital, Lucca, Italy 11 Division of Medical Oncology, IRCCS, Giovanni Paolo II Hospital, Bari, Italy 12 Medical Oncology, Catholic University of Sacred Heart, Rome, Italy 13 Department of Medical Oncology, University Campus Bio-Medico, Rome, Italy 14 Medical Oncology, Ospedale San Giovanni Calibita Fatebenefratelli, Rome, Italy 15 Oncology Unit, Sant’Andrea Hospital, “Sapienza” University of Rome, Rome, Italy 16 Medical Oncology, S. Spirito Hospital, Rome, Italy 17 Scientific Direction, “Regina Elena” National Cancer Institute, Rome, Italy 18 Department of Molecular Medicine, “Umberto I”, “Sapienza” University of Rome, Roma, Italy 19 Investigative Clinical Oncology, Fondazione del Piemonte per l’Oncologia-Candiolo Cancer Institute (IRCCs), Candiolo, Italy 20 Division of Medical Oncology, Ospedale Civile di Saluzzo, Saluzzo, Italy Correspondence to: Patrizia Vici, e-mail: pvici@ifo.it Keywords: triple positive, adjuvant breast cancer, trastuzumab, chemotherapy, hormonal receptors Received: December 01, 2015     Accepted: February 11, 2016     Published: February 18, 2016 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.