Trastuzumab-related cardiotoxicity in early breast cancer: A cohort study

Background. Concerns have been raised about the cardiac safety profile of trastuzumab for the adjuvant treatment of early stage breast cancer in clinical practice. We assessed tras- tuzumab-related cardiotoxicity and its predictors in a large co-hort of Italian women. Methods. Through a record linkage between four regional health care databases, we identified the rate of severe car-diac adverse events among women treated with trastu-zumab for early breast cancer in Lombardy. The cumulative risk of cardiotoxicity was estimated using the Kaplan-Meier method, and independent predictors were assessed using the Cox model. Results. Of 2,046 trastuzumab users, 53 (2.6%) experienced at least one hospitalization for a cardiac event, and there were two cardiac deaths. The cumulative risk of cardiotoxicity in- creased up to 2 years after starting treatment, reaching a pla-teau at 2.8%. The risk was low (0.2%) among young women, whereas the incidence was approximately 10% in women aged >70 years, irrespective of cardiovascular risk factors. Age and history of cardiac disease were strong predictors of cardiotoxicity, with a hazard ratio of 11.3 (95% confidence in-terval [CI]: 3.5-36.6) for women aged >70 years as compared with those <50 years of age. Hazard ratio was 4.4 (95% CI: 2.1-9.5) for women with a history of cardiac disease compared with those without a history of cardiac disease. Conclusions. Cardiotoxicity of trastuzumab varies consider-ably across subgroups of patients.The long-term safety profile was less favorable than in the largest clinical trial. Strategies to reduce cardiotoxicity in high-risk women should be investigated. © AlphaMed Press 2013.