title: Trastuzumab for HER2+ metastatic breast cancer in clinical practice: Cardiotoxicity and overall survival.
abstract: The evidence on efficacy and safety of trastuzumab in metastatic breast cancers (MBC) mainly derives from randomized clinical trials. We assessed short- and long-term overall survival (OS) and cardiotoxicity in a large cohort of women with MBC treated with trastuzumab in clinical settings. Using healthcare administrative data of Lombardy (10 millions inhabitants), we identified a cohort of women receiving trastuzumab for MBC between 2006 and 2009. The cumulative risk of severe cardiac events and the OS from the first trastuzumab administration were estimated using the Kaplan-Meier method. Their predictors were assessed using Cox regression models. We found 681 trastuzumab MBC users. Thirty two (4.7%) women experienced severe cardiac adverse events. The cumulative risk increased sharply, reaching a value of 2.4% and 4.3% during the first and second year; thereafter it increased of about 1% per year. Age was a strong predictor of cardiotoxicity. The OS was 81.8%, 64.0%, 50.2%, 41.1% and 37.2% at 1, 2, 3, 4 and 5 years, respectively. Independent predictors of worse OS were: age, brain liver or lung metastasis compared to other metastasis, use of taxanes and other chemotherapies, a cardiac adverse event after trastuzumab use, and a higher time between metastasis and BC diagnoses. The incidence of cardiotoxicity among women treated with trastuzumab for HER2-positive MBC appeared higher than that reported in RCTs, particularly in elder patients. In spite of this, median survival, was, if anything, better.
authors.affiliation: Department of Epidemiology, IRCSS Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. Electronic address: marta.rossi@marionegri.it.
authors.forename: Marta
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Carioli
authors.affiliation: Department of Epidemiology, IRCSS Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Bonifazi
authors.affiliation: Department of Medical Oncology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zambelli
authors.affiliation: Unit of Biostatistic and Epidemiology, Department of Statistics, University of Milano-Bicocca, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Franchi
authors.affiliation: Unit of Clinical Epidemiology, Galeazzi Orthopedic Institute-IRCCS, Milan, Italy; Department of Biomedical Sciences for Public Health, University of Milan, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moja
authors.affiliation: Unit of Biostatistic and Epidemiology, Department of Statistics, University of Milano-Bicocca, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Zambon
authors.affiliation: Unit of Biostatistic and Epidemiology, Department of Statistics, University of Milano-Bicocca, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corrao
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: La Vecchia
authors.affiliation: Operative Unit of Territorial Health Service, Health Directorate, Regione Lombardia, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Zocchetti
authors.affiliation: Department of Epidemiology, IRCSS Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Negri
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D016208:Databases, Factual; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D000068878:Trastuzumab / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Cardiotoxicity; Metastatic breast cancer; Survival; Trastuzumab