Long-term lung cancer risk in breast cancer survivors: A 40-year comprehensive analysis.

Abstract

e12501 Background: Breast cancer survivors face an increased risk of secondary malignancies, with lung cancer being one of the most concerning long-term adverse effects. This study provides a comprehensive analysis of the incidence and survival outcomes of lung cancer in breast cancer patients treated with postoperative radiotherapy, emphasizing long-term risk assessment and temporal trends over four decades. Methods: This retrospective cohort study utilized data from the Breast Cancer Health Database, encompassing 304,550 breast cancer patients diagnosed between 1979 and 2020. The association between postoperative radiotherapy and secondary lung cancer risk was evaluated using Cox proportional hazards models, adjusting for confounding variables including surgery, chemotherapy, immunotherapy, endocrine therapy, and targeted therapy. Kaplan-Meier survival analyses were conducted to evaluate overall survival, stratified by treatment modalities and diagnosis periods. Temporal trends in survival and treatment efficacy were analyzed across decades to assess the evolution of risk-benefit profiles. Results: Among the cohort, 3,112 patients were diagnosed with secondary lung cancer. Postoperative radiotherapy was associated with a significant increase in lung cancer risk (hazard ratio [HR]: 1.61; 95% confidence interval [CI]: 1.414–1.691; p < 0.0001). The median time to secondary lung cancer diagnosis was 124 months, with risk influenced by radiation exposure levels. While radiotherapy was associated with a heightened lung cancer risk, it concurrently demonstrated improved overall survival in breast cancer patients. Temporal analysis revealed enhanced survival benefits for radiotherapy recipients during more recent periods (2010–2017) compared to earlier decades, reflecting advancements in radiotherapy techniques. Stratified analysis indicated that treatment combinations influenced outcomes: chemotherapy was associated with a reduced lung cancer risk (HR: 0.845; p = 0.0001), whereas targeted therapy significantly increased risk (HR: 2.033; p < 0.0001). Conclusions: Postoperative radiotherapy in breast cancer survivors is associated with an elevated long-term risk of secondary lung cancer but offers substantial overall survival benefits. Temporal improvements in radiotherapy delivery and personalized treatment strategies have likely contributed to a more favorable risk-benefit profile in recent years. These findings underscore the critical need for long-term surveillance and the development of tailored therapeutic approaches to balance the risks and benefits of radiotherapy in breast cancer management.