Incidence of Cardiotoxicity and Validation of the Heart Failure Association-International Cardio-Oncology Society risk strati�cation Tool in Patients Treated with Trastuzumab for HER2-Positive Early Breast Cancer.

Purpose Trastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates (left ventricular ejection fraction [LVEF] decline, congestive heart failure [CHF], cardiac death or trastuzumab discontinuation) and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice. Patients receiving curative trastuzumab between 2011-2018 were identi�ed. Demographics, treatments, assessments and toxicities were recorded. Fisher’s exact test, chi-squared and logistic regression were used. were and The and cardiotoxicity: LVEF CHF NYHA class and class III-IV in and discontinuation due to cardiac in 35 deaths were The HFA-ICOS score identi�es patients at high risk of cardiotoxicity discontinuation and management of cardiac events were also compared among these patient groups. Logistical regression was used to calculate the odds of cardiac events based on HFA-ICOS risk category. The performance of the HFA-ICOS Risk Tool to predict cardiotoxicity was evaluated by calculating sensitivity, speci�city, positive predictive value (PPV) and negative predictive value (NPV). We also composed receiver-operating characteristic (ROC) curves and calculated the area under the curve for the prediction model. The HFA-ICOS Risk Tool had a sensitivity of 14.8%, a speci�city of 93.2%, a PPV of 30.3% and a NPV of 84.6% when predicting any cardiac event on trastuzumab in patients classi�ed as low/medium risk versus those classi�ed as high/very high risk. Area under the ROC curve for the predictive model for any cardiac toxicity was 0.56. LVEF decline. (13) In our series only 3.8% of patients did not complete a full one-year course of trastuzumab due to cardiac toxicity. The PERSEPHONE study suggested non-inferior e�cacy of 6 months of treatment compared with 12 months along with a substantial reduction in cardiac events from 12% to 9%. (21) there are no differences in the rates of cardiac events according to consistent with previous 66 are able to complete a one-year course of trastuzumab without complications,(22) although comorbidities remain critical cardiotoxicity. (23) has not been captured in our cohort. GLS has recently emerged as a new marker of subclinical ventricular dysfunction demonstrating a stronger association with prognosis compared with LVEF in patients with cardiac conditions not related to cancer. (25) Various observational studies suggested its potential role accurately to predict the cardiotoxicity of anticancer agents and guide cardioprotective treatment. (26, 27) Our analysis is retrospective and therefore may be subject to selection bias as we included patients who were deemed �t to receive trastuzumab. Finally, excluding patients who did not receive a full course of trastuzumab at our institution may have also contributed to selection bias.