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Risk of severe cardiotoxicity following treatment with trastuzumab: a meta-analysis of randomized and cohort studies of 29,000 women with breast cancer

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Abstract

Trastuzumab prolongs survival in women with HER2-positive breast cancer, but may increase the risk of heart disease. The occurrence of severe cardiotoxicity, however, is not defined in real-life settings. We performed a meta-analysis of clinical trials and cohort studies to estimate the frequency of cardiotoxicities following trastuzumab treatment. We searched MEDLINE, EMBASE, and the Cochrane Library (1996–January 2014). The primary outcome was the frequency of severe cardiotoxicities up to 3-years after trastuzumab initiation. Among 58 studies (29,598 patients), severe cardiotoxicity occurred in 3.00 % (95 % CI 2.41–3.64), 2.62 % (95 % CI 1.97–3.35), and 3.14 % (95 % CI 2.12–4.37) of overall, early (EBC) and metastatic (MBC) breast cancer patients, respectively. In EBC, the proportion increased from 2.40 % at the first year to a plateau of approximately 3 % after the second year. In MBC, the proportion increased from 3.00 to 3.68 % when trastuzumab was used as first line or further lines of therapy, respectively. In EBC, cardiotoxicity occurred in 2.90 % of patients treated with taxanes and anthracyclines compared to 0.92 % in patients treated with taxanes without anthracyclines. The occurrence of cardiotoxicity varied according to age, increasing from 2.31 % in individuals <50 years, to 3.46 % in those 50–59 years, to 4.91 % in those >60 years of age. Cardiotoxicity was higher in smokers (5.3 %), dyslipidemic patients (3.9 %), BMI ≥25 (6.5 %), diabetes (6.2 %), hypertension (5.5 %), or positive history of cardiac disease (19.1 %). RCTs consistently report lower cardiac toxicity rates than observational studies (EBC: 1.7 versus 3.2; MBC: 2.8 versus 4.4). Following trastuzumab initiation, approximately three in 100 patients develop severe cardiotoxicity after 2 years. Patients enrolled in cohort studies, who more closely reflect women treated for breast cancer in real-life settings compared to RCTs, are at higher risk of developing cardiac events.

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Acknowledgments

Dr. Bonifazi was supported by a fellowship from the Italian Foundation for Cancer and Research (FIRC).

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Stefania Mantarro & Corrado Blandizzi

  2. Department of Epidemiology, IRCSS Institute for Pharmacological Research “Mario Negri”, Milan, Italy

    Marta Rossi, Martina Bonifazi & Eva Negri

  3. Department of Clinical Medicine and Community Health, University of Milan, Milan, Italy

    Marta Rossi & Carlo La Vecchia

  4. Italian Cochrane Centre, University of Modena and Reggio Emilia, Modena, Italy

    Roberto D’Amico

  5. Department of Biomedical Sciences for Public Health, University of Milan, Via Carlo Pascal 36, 20133, Milan, Italy

    Lorenzo Moja

  6. Clinical Epidemiology Unit, IRCCS Orthopedic Institute Galeazzi, Milan, Italy

    Lorenzo Moja

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  1. Stefania Mantarro
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Mantarro, S., Rossi, M., Bonifazi, M. et al. Risk of severe cardiotoxicity following treatment with trastuzumab: a meta-analysis of randomized and cohort studies of 29,000 women with breast cancer. Intern Emerg Med 11, 123–140 (2016). https://doi.org/10.1007/s11739-015-1362-x

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