ABSTRACT: Importance:No comprehensive data are available regarding the frequency of breast biopsies performed during follow-up of treatment for invasive breast cancer. Objective:To determine how often patients treated for breast cancer require breast biopsies during follow-up. Design, Setting, and Participants:This nationwide population-based cohort study included 41 510 patients 64 years or younger in a commercial insurance database and 80 369 patients 66 years or older in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were diagnosed with incident invasive breast cancer (stages I-III) from January 1, 2000, through December 31, 2011. Diagnosis and procedural codes were used to identify biopsy rates during follow-up. Data were analyzed from March 3 through October 3, 2017. Main Outcomes and Measures:Cumulative incidence and adjusted risk of breast biopsy and subsequent breast cancer treatment were calculated using the Kaplan-Meier method and Cox proportional hazards regression. All statistical tests were 2 sided. Results:Among the 121 879 patients in the study population, 5- and 10-year overall incidences of breast biopsy were 14.7% and 23.4%, respectively, in the commercial insurance cohort and 11.8% and 14.9%, respectively, in the SEER-Medicare cohort. The 5-year estimated incidence of breast biopsy was higher among women treated with brachytherapy (24.0% in the commercial insurance and 25.0% in the SEER-Medicare cohorts) than among those treated with whole-breast irradiation (16.7% in the commercial insurance and 15.1% in the SEER-Medicare cohorts) and persisted after multivariate adjustment in the commercial insurance (hazard ratio [HR], 1.53; 95% CI, 1.38-1.70; P < .001) and SEER-Medicare (HR, 1.76; 95% CI, 1.63-1.91; P < .001) cohorts. Adjuvant chemotherapy use (HR, 1.31; 95% CI, 1.25-1.37; P < .001) and patient age (>85 vs 66-69 years; HR, 0.40; 95% CI, 0.36-0.44; P < .001) in the SEER-Medicare cohort and endocrine therapy in the commercial insurance (HR, 0.88; 95% CI, 0.82-0.93; P < .001) and SEER-Medicare (HR, 0.91; 95% CI, 0.85-0.97; P = .002) cohorts were independently associated with biopsy. After unilateral mastectomy, the estimated 5-year contralateral breast biopsy rates were 10.4% and 7.7% in the commercial insurance and SEER-Medicare cohorts, respectively. Of the patients with breast biopsy, 1239 of 4158 patients (29.8%) in the commercial insurance cohort and 2258 of 9747 patients (23.2%) in the SEER-Medicare cohort underwent subsequent cancer treatment. Conclusions and Relevance:These data on the need for breast biopsies during follow-up and subsequent treatments from a large cohort of women with commercial insurance and Medicare can be used in the context of therapy-planning discussions and survivorship expectations for patients with breast cancer.