Few studies have examined aromatase inhibitor therapy relating to role function in breast cancer survivors of working age. Our study sought to identify how pre-therapy sociodemographic and health/treatment-related characteristics, as well as patient-reported symptoms measured every six-months, influence role function during 18months of AI therapy for early-stage breast cancer. We performed a secondary analysis of longitudinal study data using linear mixed-effects modeling to examine role physical (RP) and role emotional (RE) functioning measured with the Medical Outcome Study Short Form 36 v2. The sample of postmenopausal women (N = 351) consisted of three cohorts: chemotherapy followed by anastrozole (CFAI), anastrozole only (AI only), and non-cancer controls. Our choice of variables and interpretation of findings was theoretically based on the Cancer Survivorship and Work Model. Stepwise backward deletion determined which predictors to include in the final model, accounting for treatment group. Both treatment groups were associated with greater limitations in RP functioning than controls. CFAI had twice the impact on RP compared to AI only. While the RP model displayed significant predictors across sociodemographic, health/treatment, and symptom characteristics, only symptoms were associated with greater limitations in RE functioning. Findings were significant at p < .05. Transitioning from acute to extended survivorship is a critical juncture in which multiple factors place breast cancer survivors at risk of diminished role function. Early interventions to address role function limitations during systemic treatment may lead to better work outcomes and improve the quality of long-term survivorship.