Due to improved detection and treatment, survival rates among breast cancer survivors (BSC) have increased. However, BCS may experience cognitive impairment (CI) following treatment, which has been reported by BCS up to 10 years after chemotherapy (CT). There is limited evidence on whether stress- reducing interventions improve CI in BSC. The primary goal of this application is to establish the Mindfulness- Based Stress Reduction for Breast Cancer (MBSR(BC)) program as an effective treatment for CI in BCS. Specifically we aim to (1) evaluate the extent to which MBSR(BC) compared to the Breast Cancer-Education Support (BCES) program or Usual Care (UC) improves cognitive functioning among BCS off treatment; (2) determine if improvements in cognitive functioning achieved from MBSR(BC) are mediated through increased mindfulness and decreased rumination and stress; (3) evaluate genetic variants as moderators of MBSR(BC) on improvements in CI; and (4) determine the impact of MBSR(BC) on healthcare utilization and costs. To achieve these aims, we will conduct a randomized controlled trial (RCT) among 330 BCS with Stage I-III BC who have received adjuvant CT or CT and radiation. Within this RCT, MBSR(BC) will be delivered to a subpopulation of Spanish speaking BCS. Participants will be randomly assigned in a 1:1:1 ratio to (1) the 6- week MBSR(BC) program; (2) the 6-week BCES program; or (3) UC. The BCES program will match the MBSR(BC) program for time and attention and parallel the group support component of MBSR(BC). Assessments will take place at baseline, 6 weeks,12 weeks and 6 months and include clinical history and demographic information, objective neuropsychological assessments, subjective cognitive and symptom measurements, cost utilization surveys and a blood sample collection for genetic analyses. This study is highly innovative to be the first randomized trial to: 1) evaluate the efficacy of MBSR(BC) among BCS for objective neuropsychological and subjective improvements in cognitive functioning; 2) evaluate genetic profiles as moderators of MBSR(BC) on improving CI; 3) offer the MBSR trial in Spanish in addition to English for the purpose of improving cognition; and 4) determine the effect of MBSR(BC) on CT-induced CI among BCS related to health service utilization costs. MBSR(BC) provides training to promote stress reduction through self-regulation of attention and awareness to stressful events. Our preliminary results show that MBSR(BC) improves subjective cognitive functioning. If MBSR(BC) is found to be effective, it will provide evidence of a viable non-pharmacological method for managing CI in BCS. Additionally, the examination of the effects of the hypothesized mediators may yield new insights for tailoring MBSR(BC) and/or developing additional interventions to aid BCS. The assessment of genetic polymorphisms to explore if risk alleles are associated with improvement in cognitive functioning may demonstrate that specific genetic profiles may modify improvements in CI for those receiving MBSR(BC). Finally, if MBSR(BC) is shown to be effective, this may significantly impact healthcare utilization and cost and produce necessary evidence for clinicians, researchers and policymakers.