Risk factors and specific cancer types of second primary malignancies in patients with breast cancer receiving adjuvant radiotherapy: a case-control cohort study based on the SEER database.

Patients with breast cancer can survive and live a long, cancer-free life; however, late complications of treatment, such as second primary malignancies (SPMs), have emerged as a competing cause of death and morbidity. We conducted a long-term population-based cohort study to identify the risk factors for SPMs and specific secondary cancer types after various latency periods of irradiated breast cancer. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) for independent risk factors for SPM. We also calculated the HR of each specific cancer type and the latency time to specific SPMs. The risk of SPM was statistically significantly higher in patients with adjuvant RT than in patients without adjuvant RT (adjusted HR [aHR]: 1.105, 95% CI: 1.013-1.206). Compared with the control group, the case group had significantly increased risks of contralateral breast cancer (aHR: 1.268, 95% CI: 1.112-1.445), lung cancer (aHR: 1.218, 95% CI: 1.049-1.565), and urinary system cancer (aHR: 1.702, 95% CI: 1.140-2.543). Adjuvant RT for breast cancer increases the risk of SPM. Contralateral breast cancer, lung cancer, and bladder cancer were significant SPMs after breast RT, although the cumulative risk of SPM was low, at approximately 6, 10, and 13 cancers per 1000 women with irradiated breasts at latency periods of 5, 10, and 15 years, respectively, after breast RT.