Epidemiology of interstitial lung disease in patients with metastatic breast cancer at baseline and after treatment with HER2-directed therapy: a real-world data analysis

Abstract Purpose: Using real-world data, interstitial lung disease (ILD) prevalence before and after HER2-directed therapy was estimated. Potential ILD risk factors in patients receiving HER2-directed therapy for metastatic breast cancer (mBC) were evaluated. Methods: Adults with HER2-directed therapy for mBC initiated between September 25, 1998 and February 22, 2020 were included. ILD was defined broadly as one or more of 64 lung conditions. Patients were followed until incident ILD, death, last contact, or study end. Results: 533 patients were identified with median age at mBC of 57, 51% had de novo mBC, 43% ever smokers, 30% had lung metastases, 9% thoracic radiation, 6% chronic obstructive pulmonary disease (COPD), and 16% had prevalent ILD. ILD cumulative incidence at one year was 9% (95% CI: 6%, 12%), with a median follow-up of 23 months. Smoking (HR = 2.2, 95% CI: 1.1, 4.8) and Black/African-American race (HR = 3.4, 95% CI: 1.6, 7.5) were significantly associated with ILD; HRs for pre-existing lung conditions (HR = 1.8, 95% CI: 0.9, 3.8) and thoracic radiation (HR = 2.3, 95% CI: 0.8, 7.1) were not statistically significant. Prevalent ILD was associated with 13-fold greater occurrence of incident ILD. 85% of patients with prevalent or incident ILD were symptomatic. Conclusions: This real world population of patients with mBC had a high prevalence of ILD prior to HER2 directed therapy, reflecting the multifactorial causation of interstitial lung changes. The cumulative incidence of ILD in patients receiving HER2 directed therapy for mBC augment prior reports. Symptomatic presentation suggests an opportunity for early intervention.