CDK4/6 inhibitor-related interstitial lung disease in breast cancer: a single-center case series and literature-based patient-level review.

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are widely used in the treatment of breast cancer. CDK4/6 inhibitor-related interstitial lung disease (ILD) is uncommon but potentially serious, and its clinical manifestations, radiologic patterns, and outcomes remain incompletely characterized. This study aimed to characterize the clinical presentation, radiologic patterns, diagnostic evaluation, treatment, and outcomes of CDK4/6 inhibitor-related ILD using a Chinese single-center case series and an updated literature-based patient-level review. Methods: Seven patients with clinically diagnosed CDK4/6 inhibitor-related ILD were retrospectively identified at our center between November 2022 and February 2026. Clinical data, chest imaging, bronchoscopy and bronchoalveolar lavage fluid (BALF) findings when available, treatment, and outcomes were collected. An updated patient-level literature review was performed through May 30, 2026 using PubMed, Web of Science, and Google Scholar. Results: A total of 60 cases were analyzed, including seven institutional cases and 53 published cases. The median interval from CDK4/6 inhibitor initiation to ILD onset or diagnosis was 139 days among 59 cases with available latency data, and 24 cases (40.7%) occurred within 3 months. Thirty patients had received palbociclib, 22 had received abemaciclib, and eight had received ribociclib. Fatal outcomes occurred in nine patients. The most frequently reported symptoms were cough and dyspnea, whereas severe cases progressed to hypoxemic respiratory failure. Chest computed tomography (CT) findings were heterogeneous, including ground-glass opacities (GGOs), interlobular septal thickening, patchy consolidations, and radiologic patterns classified as nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), hypersensitivity pneumonitis (HP)-like, and acute interstitial pneumonia/acute respiratory distress syndrome (AIP/ARDS)-like. Among eight patients with an AIP/ARDS-like pattern, five died and three had non-fatal outcomes. In the institutional cases, no pathogen was detected in available BALF cultures, and lymphocytic predominance was observed in cases with cell differential data. Conclusions: CDK4/6 inhibitor-related ILD should be considered when new respiratory symptoms or new CT abnormalities occur during CDK4/6 inhibitor therapy. Because its presentation is nonspecific, evaluation should focus on high-resolution CT (HRCT) assessment, exclusion of infection, tumor progression and radiation-related lung injury, and severity-based decisions regarding drug interruption or discontinuation. BALF is most useful when infection remains a major competing diagnosis.