Abstract P2-12-05: Retrospective Study of Drug-Induced Interstitial Lung Disease in Breast Cancer Patients Treated at Mayo Clinic between the Years of 2018-2023 (Real World Experience)

Abstract Background: Breast cancer treatment has seen significant advancements in recent years, particularly with the introduction of immune checkpoint inhibitors, antibody-drug conjugates, and CDK 4/6 inhibitors. Despite these improvements, side effects remain a major concern. Drug-induced interstitial lung disease (DIILD), a subtype of diffuse parenchymal lung disease, occurs at different rates with different drugs posing a significant challenge for the treating medical oncologist. Understanding the real-world incidence of DIILD with newer breast cancer drugs is essential for enhancing patient outcomes. Methods: In this retrospective study, we reviewed patients diagnosed with DIILD at Mayo Clinic Comprehensive Cancer Center from January 2018 to December 2023. Using Mayo Clinic’s informatics tool, Mayo Data Explorer, with keywords “drug-induced,” “pneumonitis,” “lung injury,” and “interstitial lung disease,” and ICD codes for breast cancer (n=304), 101 patients were identified. All cases were reviewed by a pulmonologist to confirm the diagnosis. Patients with alternative diagnoses were excluded. Pneumonitis grading was based on NCI CTCAE v6.0 guidelines. Statistical analyses included Kruskal-Wallis tests and Fisher’s exact tests. Results: Among the 101 breast cancer patients with DIILD, 89% were white, the median age was 62.7 years (IQR: 54-69.9), and 94.1% had good performance status (ECOG 0-2). Median BMI was 27.9 (IQR: 23.3-32.9), with 33.7% having a smoking history. Comorbidities included prior radiation (51.5%), lung disease (COPD 6.9% & asthma 15.8%), prior COVID-19 infection (24.8%), and CKD (16.8%, with 11.8% stage IV/V). Tumor characteristics: 61.4% were estrogen positive 25.7% HER2 positive and 12.9% triple negative. Disease stages: 47.5% of patients were in early-stage (stages I-III), while 56.4% were metastatic (stage IV). Forty-five patients required hospitalization, five required intubation (11.4%), and there were three deaths (all associated with fam-trastuzumab deruxtecan). Common culprit drugs included fam-trastuzumab deruxtecan (20%), everolimus (15.8%), abemaciclib (12.9%), and pembrolizumab (11.9%). Median time to DIILD diagnosis: 111 days (IQR: 69-210) with specific median times of 173.5 days for fam-trastuzumab deruxtecan, 95.5 days for everolimus, 205 days for abemaciclib and 85 days for pembrolizumab. Regarding treatment, 78.2% received high-dose corticosteroids, 1% mycophenolate, and 7.9% other treatments. Seventeen patients were rechallenged with the culprit medication and 47% experienced recurrence. More than half (57.4%) resolved within six months, with a median resolution time of 62.5 days (IQR: 41-110). We analyzed for predictors of grade severity, with DIILD severity defined as low-grade (grades 1-2, 56.4%) and high-grade (grades 3-5, 43.6%). COPD was the only significant predictor, with COPD being more common in patients with higher ILD grade (13.6% vs. 1.8%, p=0.041). Of note, a history of prior COVID-19 infection was not predictive of DIILD severity. Conclusion: This study provides real-world experience on DIILD in breast cancer patients, identifying common culprit drugs and highlighting an association of higher ILD grading with COPD. The variability in time to DIILD diagnosis underscores the need for vigilant monitoring. High-dose corticosteroids were effective, but rechallenge posed a high recurrence risk, indicating the complexity of managing DIILD. Future research is needed to identify individualized genomic predictors of lung toxicity. Citation Format: John Fanous, Farah Raheem, Alejandro Diaz-Arumir, Ana Zamora Martinez, Claire Yee, Lida Mina. Retrospective Study of Drug-Induced Interstitial Lung Disease in Breast Cancer Patients Treated at Mayo Clinic between the Years of 2018-2023 (Real World Experience) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-12-05.