ABSTRACT: Brachytherapy after lumpectomy is an increasingly popular breast cancer treatment, but data concerning its effectiveness are conflicting. Recently proposed "suitability" criteria guiding patient selection for brachytherapy have never been empirically validated.Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we compared women aged 66 years or older with invasive breast cancer (n=28,718) or ductal carcinoma in situ (n=7229) diagnosed from 2002 to 2007, treated with lumpectomy alone, brachytherapy, or external beam radiation therapy (EBRT). The likelihood of breast preservation, measured by subsequent mastectomy risk, was compared by use of multivariate proportional hazards, further stratified by American Society for Radiation Oncology (ASTRO) brachytherapy suitability groups. We compared 1-year postoperative complications using the ?(2) test and 5-year local toxicities using the log-rank test.For patients with invasive cancer, the 5-year subsequent mastectomy risk was 4.7% after lumpectomy alone (95% confidence interval [CI], 4.1%-5.4%), 2.8% after brachytherapy (95% CI, 1.8%-4.3%), and 1.3% after EBRT (95% CI, 1.1%-1.5%) (P<.001). Compared with lumpectomy alone, brachytherapy achieved a more modest reduction in adjusted risk (hazard ratio [HR], 0.61; 95% CI, 0.40-0.94) than achieved with EBRT (HR, 0.22; 95% CI, 0.18-0.28). Relative risks did not differ when stratified by ASTRO suitability group (P=.84 for interaction), although ASTRO "suitable" patients did show a low absolute subsequent mastectomy risk, with a minimal absolute difference in risk after brachytherapy (1.6%; 95% CI, 0.7%-3.5%) versus EBRT (0.8%; 95% CI, 0.6%-1.1%). For patients with ductal carcinoma in situ, EBRT maintained a reduced risk of subsequent mastectomy (HR, 0.40; 95% CI, 0.28-0.55; P<.001), whereas the small number of patients treated with brachytherapy (n=179) precluded definitive comparison with lumpectomy alone. In all patients, brachytherapy showed a higher postoperative infection risk (16.5% vs 9.9% after lumpectomy alone vs 11.4% after EBRT, P<.001); higher incidence of breast pain (22.9% vs 11.2% vs 16.7%, P<.001); and higher incidence of fat necrosis (15.3% vs 5.3% vs 7.7%, P<.001).In this study era, brachytherapy showed lesser breast preservation benefit compared with EBRT. Suitability criteria predicted differential absolute, but not relative, benefit in patients with invasive cancer.