Abstract Purpose:This study was performed to analyze the risk of second non-breast primary cancers (2nd_PrimaryCa) among Korean women who had received curative treatment for breast cancer. Methods:By using data from the Korean National Health Insurance Service Database between 2002 and 2017, we identified 399,621 women with invasive breast cancer. To analyze the long-term risk of 2nd_PrimaryCa, we included 52,506 women who underwent curative surgery between 2003 and 2008, and no history of cancers before the date of breast cancer surgery. The cumulative incidence of 2nd_PrimaryCa was estimated using the Kaplan-Meier analysis. Cox regression analysis was used to analyze the association between 2nd_PrimaryCa occurrence and factors including age, income level, receipt of systemic treatment or radiotherapy, family history of cancers, alcohol intake, and BRCA gene mutations.Results:A total of 3,084 (5.87%) patients developed 2nd_PrimaryCa. The 10-year incidence of 2nd_PrimaryCa was 5.78% (range, 5.56 – 6.00%). The median time to 2nd_PrimaryCa was 7.61 years (range, 6.22 – 9.31 years). Types of organs involved by 2nd_PrimaryCa were as followings: thyroid (18.84%), gynecological organs (12.78%), hepatobiliary structures (12.48%), thorax (11.25%), lower gastrointestinal (GI) tract (9.63%), upper GI tract (9.18%), skin (4.22%), lymphoma or leukemia (4.09%), brain (3.15%), head and neck (2.56%), and others (11.84%). The risk of 2nd_PrimaryCa was significantly associated with ≥ 60 years of age (hazard ratio (HR) = 2.15, 95% confidence interval (CI) = 1.60 – 2.90, p < 0.01), Medical Aid recipients (HR = 8.79, 95% CI = 6.73 – 10.85, p < 0.01), and receipt of chemotherapy and endocrine therapy (HR = 1.27, 95% CI = 1.12 – 1.43, p < 0.01). Radiotherapy was related to lower incidence of 2nd_PrimaryCa (HR = 0.87, 95% CI = 0.81 – 0.94, p < 0.01). Alcohol intake, family history of cancer, or carrying BRCA gene mutations was not related to the risk of 2nd_PrimaryCa. Among the patients with 2nd_PrimaryCa, the 5-year overall survival (OS) rate was 67.28% after the diagnosis of 2nd_PrimaryCa. Age of ≥ 60 years (HR = 1.67, 95% CI = 1.01 – 2.78, p = 0.04) and receiving chemotherapy and endocrine therapy (HR = 1.88, 95% CI = 1.43 – 2.46, p < 0.01) were significantly related to inferior OS. Conclusions:The risk of 2nd_PrimaryCa was associated with personal and treatment factors in Korean patients with breast cancer. These factors are needed to be considered in the surveillance of breast cancer survivors. Citation Format: Haeyoung Kim, Su SSan Kim, Ji Sung Lee, Jae Sun Yoon, Hyuk Jai Shin, Jeong Eon Lee, Sei Kyung Lee, Il Yong Chung, So-Youn Jung, Young Jin Choi, Korean Breast Cancer Society. Risk of second primary cancers after curative treatment of breast cancer: A Korean nationwide population-based study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-25.