title: Triple positive breast cancer: a distinct subtype?
abstract: Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decreased overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct subtypes, with dissimilar clinical behavior and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the "standard" treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets.
authors.affiliation: Division of Medical Oncology B, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: pvici@ifo.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
authors.affiliation: Division of Medical Oncology B, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: pizzuti8@hotmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Pizzuti
authors.affiliation: Department of Experimental and Clinical Sciences, University "G. d'Annunzio", V dei Vestini, 29, 66100 Chieti, Italy. Electronic address: natoli@unich.it.
authors.forename: Clara
authors.initials: C
authors.lastname: Natoli
authors.affiliation: Medical Oncology Unit ASL Frosinone, V Armando Fabi, 03100 Frosinone, Italy. Electronic address: t.gamucci@libero.it.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gamucci
authors.affiliation: Division of Medical Oncology B, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: dilauro@ifo.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Lauro
authors.affiliation: Division of Medical Oncology B, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy; Scientific Direction, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: maddalena.barba@gmail.com.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Barba
authors.affiliation: Division of Medical Oncology B, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: sergidome@libero.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Sergi
authors.affiliation: Department of Surgery, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: claudiobotti@mac.com.
authors.forename: Claudio
authors.initials: C
authors.lastname: Botti
authors.affiliation: Oncology Unit I, Azienda Ospedaliera Universitaria Pisana, V Roma 67, 56126 Pisa, Italy. Electronic address: a.michelotti@med.unipi.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Michelotti
authors.affiliation: Division of Medical Oncology, Department of Oncology, Belcolle Hospital, ASL Viterbo, Strada S. Martinese, 01100 Viterbo, Italy. Electronic address: luca.moscetti@asl.vt.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Moscetti
authors.affiliation: Department of Gynecologic Oncology, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy; HPV Unit, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: luciorm55@gmail.com.
authors.forename: Luciano
authors.initials: L
authors.lastname: Mariani
authors.affiliation: Division of Medical Oncology B, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: izzo@ifo.it.
authors.forename: Fiorentino
authors.initials: F
authors.lastname: Izzo
authors.affiliation: Department of Medical Oncology, University Campus Bio-Medico, V Álvaro del Portillo 21, 00128 Rome, Italy. Electronic address: l.donofrio@unicampus.it.
authors.forename: Loretta
authors.initials: L
authors.lastname: D'Onofrio
authors.affiliation: Biostatistics Unit, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: isperduti@yahoo.it.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.affiliation: Division of Medical Oncology B, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: f.conti@ifo.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Conti
authors.affiliation: Division of Medical Oncology, Ospedale Civile di Saluzzo, V Spielberg 58, 12100 Saluzzo (CN), Italy. Electronic address: valentina.rossi@aslcn1.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rossi
authors.affiliation: Division of Medical Oncology, Catholic University of Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy. Electronic address: alessandra.cassano@rm.unicatt.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cassano
authors.affiliation: Division of Medical Oncology B, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy; Scientific Direction, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: maugeri.marcello@gmail.com.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maugeri-Saccà
authors.affiliation: Department of Pathology, "Regina Elena" National Cancer Institute, V Elio Chianesi 53, 00144 Rome, Italy. Electronic address: mottolese@ifo.it.
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.affiliation: Oncology Unit, Sant'Andrea Hospital, "Sapienza" University of Rome, V Grottarossa 1035/1039, 00189 Rome, Italy. Electronic address: paolo.marchetti@hotmail.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D010641:Phenotype; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000037:antagonists & inhibitors; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Anti-HER-2 agents; Breast cancer; Chemotherapy; Hormonal therapy; Triple positive