To assess risks of secondary malignancies in breast cancer patients who received radiation therapy compared to patients who did not.

The SEER database was used to identify females with a primary diagnosis of breast cancer as their first malignancy, during 1973-2008. We excluded patients with metastatic disease, age <18 years, no definitive surgical intervention, ipsilateral breast cancer recurrence, or who developed a secondary malignancy within 1 year of diagnosis. Standardized incidence ratios and absolute excess risk were calculated using SEER*Stat, version 8.2.1 and SAS, version 9.4.

There were 374,993 patients meeting the inclusion criteria, with 154,697 who received radiation therapy. With a median follow-up of 8.9 years, 13% of patients (49,867) developed a secondary malignancy. The rate of secondary malignancies was significantly greater than the endemic rate in breast cancer patients treated without radiation therapy, (O/E 1.2, 95% CI 1.19-1.22) and with radiation therapy (O/E 1.33, 95% CI 1.31-1.35). Approximately 3.4% of secondary malignancies were attributable to radiation therapy. The increased risk of secondary malignancies in breast cancer patients treated with radiation therapy compared to those without was significant regardless of age at breast cancer diagnosis (p < 0.01) and more pronounced with longer latency periods.

There was an increased risk of secondary malignancies for breast cancer patients both with and without radiation therapy compared to the general population. There was an increased risk in specific sites for patients treated with radiation therapy. This risk was most evident in young patients and who had longer latency periods.