title: SAFE trial: an ongoing randomized clinical study to assess the role of cardiotoxicity prevention in breast cancer patients treated with anthracyclines with or without trastuzumab.
abstract: Over the years, thanks to the addition of new generation systemic agents, as well as the use of more advanced and precise radiotherapy techniques, it was able to obtain a high curability rate for breast cancer. Anthracyclines play a key role in the treatment of breast disease, with a well-known benefit on disease-free survival of patients with positive nodal status. Trastuzumab have shown a significant outcome advantage after 1-year administration in case of HER2-positive disease. Unfortunately, significant increase in cardiotoxicity has been observed after anthracyclines and trastuzumab therapies. Even though the cardiology and oncology community strongly recommend a cardiotoxicity prevention strategy for this subset of patients, there is still no consensus on the optimal patient's approach. We aimed to review the published and ongoing researches on cardioprevention strategies and to present the SAFE trial (CT registry ID: NCT2236806; EudraCT number: 2015-000914-23). It is a randomized phase 3, four-arm, single-blind, placebo-controlled study that aims to evaluate the effect of bisoprolol, ramipril or both drugs, compared to placebo, on subclinical heart damage evaluated by speckle tracking cardiac ultrasound in non-metastatic breast cancer patients.
authors.affiliation: Azienda Ospedaliero Universitaria Careggi - University of Florence, Largo G.A. Brambilla 3, 50134, Florence, Italy. icro.meattini@unifi.it.
authors.forename: Icro
authors.identifier: 0000-0002-1861-2895
authors.initials: I
authors.lastname: Meattini
authors.affiliation: Early Drug Development for Innovative Therapies Division, European Institute of Oncology, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
authors.affiliation: Azienda Ospedaliero Universitaria Careggi - University of Florence, Largo G.A. Brambilla 3, 50134, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Terziani
authors.affiliation: Azienda Ospedaliero Universitaria Careggi - University of Florence, Largo G.A. Brambilla 3, 50134, Florence, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Becherini
authors.affiliation: Breast Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Airoldi
authors.affiliation: Medical Oncology Unit, Presidio Ospedaliero Felice Lotti, Pontedera, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Allegrini
authors.affiliation: UOC di Oncologia, Ospedale Versilia, Istituto Toscano Tumori, Lido di Camaiore, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Amoroso
authors.affiliation: Dipartimento Oncologico ASST - Bergamo Ovest, Treviglio, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
authors.affiliation: Medical Oncology Unit, Ospedale Misericordia, Grosseto, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bengala
authors.affiliation: Division of Medical Oncology 2, Istituto Oncologico Veneto, Padua, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Guarneri
authors.affiliation: Medical Oncology Unit, Azienda Ospedaliera Sant'Andrea, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Breast Unit, Santa Maria Annunziata Hospital, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Martella
authors.affiliation: SC Oncologia, Ospedale Ss. Antonio e Biagio e C. Arrigo, Alessandria, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Piovano
authors.affiliation: Azienda Ospedaliero Universitaria Careggi - University of Florence, Largo G.A. Brambilla 3, 50134, Florence, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Vannini
authors.affiliation: Azienda Ospedaliero Universitaria Careggi - University of Florence, Largo G.A. Brambilla 3, 50134, Florence, Italy.
authors.forename: Isacco
authors.initials: I
authors.lastname: Desideri
authors.affiliation: Medicina Interna 1, Ospedale San Giuseppe, Empoli, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tarquini
authors.affiliation: Azienda Ospedaliero Universitaria Careggi - University of Florence, Largo G.A. Brambilla 3, 50134, Florence, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Galanti
authors.affiliation: Azienda Ospedaliero Universitaria Careggi - University of Florence, Largo G.A. Brambilla 3, 50134, Florence, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Barletta
authors.affiliation: Azienda Ospedaliero Universitaria Careggi - University of Florence, Largo G.A. Brambilla 3, 50134, Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Livi
mesh_terms: D018943:Anthracyclines / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D017298:Bisoprolol / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D066126:Cardiotoxicity / Q000517:prevention & control*; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D017257:Ramipril / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D018943:Anthracyclines; D002316:Cardiotonic Agents; D017257:Ramipril; D000068878:Trastuzumab; D017298:Bisoprolol
keywords: Adjuvant anthracyclines; Beta-blockers; Breast cancer; Cardiotoxicity prevention; Trastuzumab