ArticleBreast cancer research : BCR2025
Incidence and risk factors for pneumonitis due to trastuzumab Deruxtecan in metastatic breast cancer: a retrospective cohort study.
Article in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Trastuzumab Deruxtecan-Induced Interstitial Lung Disease: A Systematic Review and Meta-Analysis of Clinical Trials and Real-World Evidence.Cancer control : journal of the Moffitt Cancer CenterPooled it
- Trastuzumab Deruxtecan-Associated Pneumonitis in Non-Breast Solid Tumors: A Retrospective Cohort Study.Journal of immunotherapy and precision oncology · 2026Article
- Real-world clinical outcomes of Trastuzumab Deruxtecan in HER2-expressing ovarian and endometrial Cancer.Gynecologic oncology reports · 2026Article
- Pulmonary Complications of Cancer Therapy: Clinical Presentations, Imaging Patterns, and Management Strategies.Medicina (Kaunas, Lithuania) · 2026Review
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23 authors.
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Abstract
backgroundFam-trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) that targets human epidermal growth factor receptor 2 (HER2) and delivers a topoisomerase inhibitor payload. T-DXd has been effectively used to treat metastatic breast cancer but causes pneumonitis in 10–15% of cases. Risk factors associated with T-DXd pneumonitis are not well described. RESEARCH QUESTION: What are the major clinical risk factors for T-DXd pneumonitis? STUDY DESIGN AND
methodsWe conducted a retrospective study of women with metastatic breast cancer at our institution treated with T-DXd as standard of care between 2020 and 2024. We collected clinical data, including demographics, relevant review of symptoms, molecular subtypes, prior treatments, and pulmonary comorbidities, from the electronic health record. A thoracic radiologist reviewed pre-treatment scans for the presence of interstitial lung abnormalities (ILAs). Radiation exposure variables were obtained from an institutional database. Pulmonologists reviewed all cases for the development of pneumonitis. We used univariable and multivariable Cox proportional hazard models to measure the association of clinical variables with the development of pneumonitis.
resultsPneumonitis was observed in 19/203 patients (9.4%). In univariable analyses, pre-treatment shortness of breath (hazard ratio [HR] 3.9, 95% confidence interval [CI] 1.3–11.7), greater number of prior treatments (HR 1.2 per line, 95% CI 1.0-1.4), triple-negative breast cancer (HR 4.9, 95% CI 1.8–13.0), low HER-2 status (4.00 (95% CI: 1.43–11.11) and pre-treatment ILAs (HR 17, 95% CI 6.5–46) were associated with pneumonitis. In multivariable models, pre-treatment ILAs (HR 10.56, 95% CI 3.8-29.31, p < 0.0001) and HER2 (HR 0.30, 95% CI 0.09–0.96, p = 0.042) were the strongest predictors of pneumonitis, with a marginal association observed for V20 (HR 1.04, 95% CI 0.99–1.09, p = 0.081).
interpretationPre-treatment ILAs and HER2-low breast cancer are major risk factors for T-DXd pneumonitis.
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