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The effect of caregiving roles on risk of elevated depressed mood over 12 months was examined in early-stage (0-IIA) breast cancer patients and same-aged women without breast cancer. Women were interviewed 4-6 weeks, 6 months, and 12 months following definitive surgical treatment (patients) or routine screening mammogram (controls). The Center for Epidemiologic Studies-Depression Scale was administered at each interview and dichotomized for analysis (<16 [little/no depressed mood] vs. ≥16 [elevated depressed mood]). Participants were categorized as having no caregiving responsibilities, caregiving for children or other persons, or caregiving for both children and others (multiple caregiving roles). Two multivariable marginal logistic regression models with repeated measures were fit (one each for patients and controls) to examine the effect of caregiving roles on elevated depressed mood, using generalized estimating equations to account for intra-individual correlations. Of 1096 participants (mean age 58; 76% white), 1019 with caregiving data were included in the analysis. Compared with baseline, patients with multiple caregiving roles (23/521 patients) were at increased risk of elevated depressed mood at 6 months (adjusted odds ratio [aOR], 7.20; 95% confidence interval [CI], 1.17-44.46; P = 0.034), and controls with multiple caregiving roles (15/498 controls) were at decreased risk of elevated depressed mood at 12-month follow-up (aOR, 0.12; 95% CI, 0.02-0.97; P = 0.047). Patients with multiple caregiving roles were more likely while controls were less likely to report elevated depressed mood over time, suggesting a need to identify patients with multiple caregiving roles early during their treatment.