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Background: For women with ductal carcinoma in situ (DCIS), radiation therapy after conservative surgery lowers the risk of recurrence. However, emerging evidence suggests that radiation therapy confers only a marginal absolute benefit for older women with DCIS. In a cohort of older women with DCIS, we sought to determine whether radiation therapy was associated with a clinically significant benefit. Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from January 1, 1992, through December 31, 1999, we identified 3409 women aged 66 years or older treated with conservative surgery for DCIS. A proportional hazards model tested whether radiation therapy was associated with a lower risk of a combined outcome, defined as a subsequent ipsilateral in situ or invasive breast cancer reported by SEER and/or a subsequent mastectomy reported by Medicare claims. The 5-year event risk was determined for patients without and with high-risk features, which were defined as at least one of the following: age 66–69 years, tumor larger than 2.5 cm, comedo histology, and/or high grade. All statistical tests were two-sided. Results: Radiation therapy was associated with a lower risk for each component of the combined outcome (hazard ratio = 0.32, 95% confidence interval [CI] = 0.24 to 0.44). For high-risk patients, the 5-year event risk was 13.6% without radiation therapy versus 3.8% with radiation therapy (difference = 9.8%, 95% CI = 6.5 to 13.2; P<.001). For low-risk patients, the 5-year event risk was 8.2% without radiation therapy versus 1.0% with radiation therapy (difference = 7.2%, 95% CI = 3.6 to 10.9; P<.001). Among healthy women aged 66–79 years, the number needed to treat with radiation therapy to prevent one event in 5 years was 11 for high-risk patients and 15–16 for low-risk patients. Conclusion: For older women with DCIS, radiation therapy appears to confer a substantial benefit that remains meaningful even among low-risk patients. [ABSTRACT FROM AUTHOR]