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Background Breast cancer is the most common cancer among women. Second primary malignancies (SPMs) related to radiotherapy are significant complications. This study aims to investigate the correlation between radiotherapy and the occurrence of SPMs in breast cancer patients with different estrogen receptor statuses. Methods We used data from the Surveillance, Epidemiology, and End Results (SEER) database, selecting estrogen receptor(+) and estrogen receptor(−) breast cancer patients from 1990 to 2015, with SPMs as the outcome measure. Fine-Gray competing risks regression and Poisson regression were employed to analyze the relationship between radiotherapy and the risk of SPMs in different estrogen receptor status groups. Results Radiotherapy was associated with an increased risk of lung cancer, melanoma, non-Hodgkin lymphoma, and leukemia in estrogen receptor(+) patients. In estrogen receptor(−) patients, radiotherapy was linked to an increased risk of brain cancer and leukemia. The cumulative incidence, standardized incidence ratio, and subgroup analyses showed consistent results. In the dynamic assessment of radiotherapy-related risks, estrogen receptor(+) patients aged 50–70 exhibited a higher risk of leukemia and melanoma. Lung cancer risk was highest during a latency period of 20–30 years, while melanoma, non-Hodgkin lymphoma, and leukemia risks peaked within the first 10 years. For estrogen receptor(−) patients, brain cancer risk was higher between ages 50 and 70, and leukemia risk was elevated between ages 20 and 50. Conclusion Postoperative radiotherapy for breast cancer is associated with an increased risk of SPMs, with risks varying by estrogen receptor status and SPM type. Further research into the prevention of radiotherapy-related SPMs in different estrogen receptor status groups is crucial.
Zhao et al. (Mon,) studied this question.