Safety of concurrent T-DM1 and radiation therapy in HER2-positive breast cancer with residual disease after neoadjuvant chemotherapy

BACKGROUND: Trastuzumab emtansine (T-DM1) is the standard adjuvant treatment for HER2-positive breast cancer with residual disease after neoadjuvant chemotherapy. Its concurrent use with locoregional radiation therapy (RT) is increasingly common, yet data on pulmonary safety remain scarce. METHODS: This retrospective single-center study included 31 patients treated with concurrent T-DM1 and RT between April 2021 and September 2023. Eligible patients had residual HER2-positive invasive disease after neoadjuvant treatment and underwent breast or chest wall RT, with or without nodal irradiation and tumor bed boost. Clinical data, dosimetric parameters, and toxicity outcomes were collected from medical records. RESULTS: The median age was 63 years (IQR: 46-69); nine patients were smokers, and three had chronic pulmonary disease. RT included nodal irradiation in 25 patients and a boost in 22. The median RT dose was 50 Gy, with a median ipsilateral lung mean dose of 13.4 Gy and V20 of 26%. T-DM1 was administered for a median of 7.5 months, with a 42-day overlap with RT. After a median follow-up of 23 months (IQR 13.5-34), grade ≥2 acute dermatitis occurred in 30% of cases. Radiation pneumonitis (RP) grade ≥2 developed in six patients (19.4%), including one grade 3 event. On univariate analysis, chronic pulmonary disease and larger planning target volumes were associated with RP, while dosimetric parameters and smoking were not. No grade 5 toxicity was reported. CONCLUSION: Concurrent T-DM1 and RT was generally well tolerated. However, RP appeared more frequent in patients with pulmonary comorbidities and larger PTV, warranting careful selection and prospective validation.