Sex-specific Survival Patterns in Korean Breast Cancer: Explainable AI Insights from K-CURE Cohort

Abstract Background: Male breast cancer (MBC) is rare, but its incidence is increasing worldwide. Evidence regarding survival differences compared with female breast cancer (FBC) is limited. This study aimed to characterize sex-specific survival patterns in Korean breast cancer and to identify key contributing factors using explainable artificial intelligence (XAI) methods. Methods: This study utilized data from the Korean Clinical Data Utilization for Research Excellence (K-CURE), a nationwide registry of all breast cancer cases in Korea. Patients diagnosed between 2012 and 2021 were analyzed by sex. Overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using multivariable Cox proportional hazards models. XAI techniques, including SHAP and LIME, were applied to identify sex-specific contributors to survival. Results: Among 200,222 patients (846 males, 199,376 females), males showed significantly poorer OS and BCSS than females (p<.001). This disparity persisted after adjustment (male OS HR ≈1.30-1.40; BCSS HR ≈1.40-1.50). Distant stage was associated with the highest mortality risk in both sexes (male HR ≈9-12; female HR ≈10-24). Distinct sex-specific patterns were observed. In males, metabolic indicators showed opposite associations with survival: higher hemoglobin was linked to lower mortality (HR ≈0.88), whereas higher fasting blood sugar was associated with increased mortality risk (HR ≈1.04). In females, hormone and targeted therapies were associated with reduced mortality (HR ≈0.30-0.55). XGBoost models achieved moderate predictive performance for both outcomes (OS AUC ≈0.85; BCSS AUC ≈0.87). SHAP and LIME analyses consistently supported these patterns, suggesting that metabolic profiles contributed more to risk estimation in males, whereas tumor stage and treatment factors were relatively more influential in females. Conclusion: These findings indicate that sex differences in breast cancer survival arise not only from differences in overall risk profiles but also from distinct prognostic factors specific to each sex. In males, metabolic indicators were more closely associated with survival, whereas in females, tumor stage and treatment factors had greater relevance. Overall, these results reflect differing underlying mechanisms by sex and highlight the need for tailored, sex-specific management strategies in breast cancer care. Citation Format: Seohyun Ahn, Juyeon Hwang, Sun-Young Kong, Jin Ho Park, So-Youn Jung, Hyun-Jin Kim. Sex-specific survival patterns in korean breast cancer: Explainable AI insights from K-CURE Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3562.