Warning factors of metachronous uterine cancer in patients with breast cancer: a real-world nationwide cohort study.

This study aimed to explore the risk factors for metachronous uterine cancer, including age at diagnosis, stage, body mass index (BMI), medical history and tamoxifen treatment in women with breast cancer to enable tailored risk-based gynecological surveillance. A nationwide population-based cohort study was conducted. Data were retrieved from the Taiwan National Health Insurance Research Database and Taiwan Cancer Registry from 2011 to 2019. The risk of metachronous uterine cancer was analyzed by Cox regression model. There were 307 patients identified with uterine cancer among 114,906 patients with breast cancer. The incidence was 37.46 cases per 100,000 person-years among tamoxifen non-users (69 cases per 184,207 person-years). Among tamoxifen users (n = 58,227), the incidence rates were 105.52 cases (79 cases per 74,869 person-years) for <1 year of use, 111.62 cases (111 cases per 99,444 person-years) for 1-3 years, 58.19 cases (31 cases per 53,276 person-years) for 3-5 years, and 62.12 cases (17 cases per 27,366 person-years) for ≥5 years. The hazard ratio (HR) for uterine cancer was 3.06 (95 % confidence interval [CI] 2.14-4.39), 3.03 (95 % CI 2.15-4.28), 1.61 (95 % CI 1.01-2.57), and 1.77 (95 % CI 1.00-3.13) for patients on tamoxifen for <1, 1-3, 3-5, and ≥5 years. High BMI (≥25 kg/m2) was associated with an increased risk (HR 2.46, 95 % CI 1.07-5.64). Abnormal uterine bleeding was a significant predictor regardless of the clinical or sonographic diagnosis of endometrial lesions. Routine ultrasound is not recommended for the detection of metachronous uterine cancer, and gynecologic investigations should focus on breast cancer patients with high BMI, tamoxifen use, and abnormal uterine bleeding.