Work

Predictors of pneumonitis in patients treated with systemic therapy and radiotherapy for localized triple negative or HER2 positive breast cancer

Year: 2026

Type: article

Abstract: PURPOSE: The treatment of HER2-positive (HER2+) and triple negative (TN) breast cancer (BC) increasingly includes systemic therapies that can be associated with a risk of drug-induced pneumonitis and may overlap with the delivery of radiotherapy, which carries an independent risk of pneumonitis. The aim of this study is to characterize the interaction between trastuzumab-emtansine (T-DM1), pembrolizumab and radiotherapy in modulating the risk of pneumonitis in a real-world setting. METHODS: A retrospective, single institution, chart review identified patients with non-metastatic HER2+ or TN BC, who were treated with adjuvant radiotherapy between 2019 and 2024. Among this cohort the proportion with pneumonitis diagnosed within 1-year following completion of radiotherapy was evaluated. The association of grade ≥2 pneumonitis (G2P+) with clinical factors of interest was examined using univariate and multivariable logistic regression. RESULTS: Of 863 eligible patients, 528 were HER2+ and 335 were TN. Overall the rate of G2P+ was 2.8 %; 3.6 % for HER2+ and 1.5 % for TN patients. On univariate analysis, radiation treatment volume, clinical stage, and receipt of T-DM1 were associated with G2P+, however, only T-DM1 (OR = 4.16, 95 % CI = 1.59-10.92, p < 0.01) and clinical stage III vs. II (OR 2.69, 95 % CI 1.03-7.02, p = 0.04) remained significant on multivariable analysis. CONCLUSION: Overall, the probability of G2P+ in patients receiving radiotherapy for HER2+ or TN BC is low. However, concurrent T-DM1 and radiotherapy was associated with significantly higher rates of pneumonitis than previously reported, suggesting a cautionary approach when combining the two therapies.

Source: The Breast

DOI: 10.1016/j.breast.2026.104706