Research Papers:

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

Patrizia Vici _, Laura Pizzuti, Isabella Sperduti, Antonio Frassoldati, Clara Natoli, Teresa Gamucci, Silverio Tomao, Andrea Michelotti, Luca Moscetti, Stefania Gori, Editta Baldini, Francesco Giotta, Alessandra Cassano, Daniele Santini, Diana Giannarelli, Luigi Di Lauro, Domenico Cristiano Corsi, Paolo Marchetti, Valentina Sini, Domenico 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, Ruggero De Maria and Filippo Montemurro

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Oncotarget. 2016; 7:17932-17944. https://doi.org/10.18632/oncotarget.7480

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Patrizia Vici1, Laura Pizzuti1, Isabella Sperduti2, Antonio Frassoldati3, Clara Natoli4, Teresa Gamucci5, Silverio Tomao6, Andrea Michelotti7, Luca Moscetti8, Stefania Gori9, Editta Baldini10, Francesco Giotta11, Alessandra Cassano12, Daniele Santini13, Diana Giannarelli2, Luigi Di Lauro1, Domenico Cristiano Corsi14, Paolo Marchetti15, Valentina Sini15,16, Domenico Sergi1, Maddalena Barba1,17, Marcello Maugeri-Saccà1,17, Michelangelo Russillo10, Lucia Mentuccia5, Loretta D’Onofrio13, Laura Iezzi4, Angelo Fedele Scinto14, Lucia Da Ros3, Ilaria Bertolini7, Maria Luisa Basile18, Valentina Rossi19,20, Ruggero De Maria17, Filippo Montemurro19

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

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


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.

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PII: 7480