Cardiotoxicity perspective on the concurrent use of anti-HER2 agents and hypofractionated versus conventional fractionated locoregional radiotherapy in breast cancer

PURPOSE: HER2-targeted therapies (trastuzumab, T-DM1) improve outcomes in HER2-positive breast cancer but are associated with cardiotoxicity. Radiotherapy also carries cardiac risks, although hypofractionated schedules have not shown increased toxicity. This study evaluated the cardiac safety of concomitant HER2-targeted therapies with different radiotherapy regimens. METHODS: This retrospective study included 148 patients with HER2-positive breast cancer who underwent surgical resection following neoadjuvant chemotherapy between 2012 and 2023. All patients subsequently received adjuvant radiotherapy and anti-HER2 therapy. To evaluate the potential cardiotoxicity of concomitant treatment, patients were stratified according to radiotherapy fractionation schedules. Echocardiographic assessment was performed at baseline and every three months during the entire treatment period. RESULTS: Among the 148 patients, 70 (47.3%) received hypofractionated radiotherapy and 78 (52.7%) received conventional fractionation. Adjuvant trastuzumab was administered to 132 (89.2%) patients, while 16 (10.8%) received T-DM1, with a similar distribution across the two radiotherapy groups. The median follow-up was 44 months (22-150). No significant association was observed between radiotherapy fractionation or the type of adjuvant anti-HER2 therapy and cardiotoxicity. However, smoking, internal mammary node radiotherapy, higher mean heart dose, and higher heart V10 and V20 were significantly associated with increased cardiotoxicity. CONCLUSION: Concurrent anti-HER2 therapies with breast/chest wall and regional nodal irradiation, including both conventional and hypofractionated schedules, is feasible and generally safe, though cardiac-sparing techniques and careful management of patients at higher risk, including those receiving internal mammary nodal irradiation or with a history of smoking, are important to minimize cardiotoxicity.