title: "Triple positive" early breast cancer: an observational multicenter retrospective analysis of outcome.
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.
authors.affiliation: Division of Medical Oncology 2, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
authors.affiliation: Division of Medical Oncology 2, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pizzuti
authors.affiliation: Biostatistics Unit, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.affiliation: Division of Oncology, S. Anna Hospital, Ferrara, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Frassoldati
authors.affiliation: Department of Experimental and Clinical Sciences, University "G. d'Annunzio", Chieti, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Natoli
authors.affiliation: Medical Oncology Unit, ASL Frosinone, Frosinone, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gamucci
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Oncology Unit, Istituto Chirurgico Ortopedico Traumatologico, Latina, Italy.
authors.forename: Silverio
authors.initials: S
authors.lastname: Tomao
authors.affiliation: Oncology Unit I, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Michelotti
authors.affiliation: Department of Oncology, Division of Medical Oncology, Belcolle Hospital, ASL Viterbo, Viterbo, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Moscetti
authors.affiliation: Department of Oncology, Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gori
authors.affiliation: Department of Medical Oncology, S. Luca Hospital, Lucca, Italy.
authors.forename: Editta
authors.initials: E
authors.lastname: Baldini
authors.affiliation: Division of Medical Oncology, IRCCS, Giovanni Paolo II Hospital, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Giotta
authors.affiliation: Medical Oncology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cassano
authors.affiliation: Department of Medical Oncology, University Campus Bio-Medico, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.affiliation: Biostatistics Unit, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Division of Medical Oncology 2, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Lauro
authors.affiliation: Medical Oncology, Ospedale San Giovanni Calibita Fatebenefratelli, Rome, Italy.
authors.forename: Domenico Cristiano
authors.initials: DC
authors.lastname: Corsi
authors.affiliation: Oncology Unit, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Oncology Unit, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy.|Medical Oncology, S. Spirito Hospital, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sini
authors.affiliation: Division of Medical Oncology 2, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Sergi
authors.affiliation: Division of Medical Oncology 2, "Regina Elena" National Cancer Institute, Rome, Italy.|Scientific Direction, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Barba
authors.affiliation: Division of Medical Oncology 2, "Regina Elena" National Cancer Institute, Rome, Italy.|Scientific Direction, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maugeri-Saccà
authors.affiliation: Department of Medical Oncology, S. Luca Hospital, Lucca, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Russillo
authors.affiliation: Medical Oncology Unit, ASL Frosinone, Frosinone, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mentuccia
authors.affiliation: Department of Medical Oncology, University Campus Bio-Medico, Rome, Italy.
authors.forename: Loretta
authors.initials: L
authors.lastname: D'Onofrio
authors.affiliation: Department of Experimental and Clinical Sciences, University "G. d'Annunzio", Chieti, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Iezzi
authors.affiliation: Medical Oncology, Ospedale San Giovanni Calibita Fatebenefratelli, Rome, Italy.
authors.forename: Angelo Fedele
authors.initials: AF
authors.lastname: Scinto
authors.affiliation: Division of Oncology, S. Anna Hospital, Ferrara, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Da Ros
authors.affiliation: Oncology Unit I, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bertolini
authors.affiliation: Department of Molecular Medicine, "Umberto I", "Sapienza" University of Rome, Roma, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Basile
authors.affiliation: Investigative Clinical Oncology, Fondazione del Piemonte per l'Oncologia-Candiolo Cancer Institute (IRCCs), Candiolo, Italy.|Division of Medical Oncology, Ospedale Civile di Saluzzo, Saluzzo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rossi
authors.affiliation: Scientific Direction, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Ruggero
authors.initials: R
authors.lastname: De Maria
authors.affiliation: Investigative Clinical Oncology, Fondazione del Piemonte per l'Oncologia-Candiolo Cancer Institute (IRCCs), Candiolo, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Montemurro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate; D000068878:Trastuzumab / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000068878:Trastuzumab
keywords: adjuvant breast cancer; chemotherapy; hormonal receptors; trastuzumab; triple positive