Purpose: Patients with breast cancer on adjuvant chemotherapy can experience weight gain and concurrent losses in muscle mass. Exercise interventions can prevent these changes, but time and travel pose barriers to participation. The Survivor Training for Enhancing Total Health (STRENGTH) trial assessed the feasibility and impact of 2 home-based interventions. Patients and Methods: Ninety premenopausal patients with breast cancer on adjuvant chemotherapy were randomized to a calcium-rich diet (CA) intervention (attention control) or to 2 experimental arms: a CA + exercise (EX) arm or a CA + EX and high fruit and vegetable, low-fat diet (FVLF) arm. Exercise arms included aerobic and strength-training exercises. Body composition, weight status, waist circumference, dietary intake, physical activity, quality of life, anxiety, depression, serum lipids, sex-hormone binding globulin, insulin, proinsulin, C-reactive protein, interleukin-1B, and tumor-necrosis factor receptor-II were measured at baseline and at 6-month follow-up. Results: Accrual targets were achieved and modest attrition was observed (8.8%). Self-reports suggest increased calcium intakes in all arms, and higher fruit and vegtable and lower fat intake in the CA + EX + FVLF arm; no differences in physical activity were observed. While measures of adiposity were generally lower in the CA + EX + FVLF arm, the only significant difference was in percentage of body fat (arms and legs); change in scores (mean ± standard deviation) were +0.7% ± 2.3% (CA); +1.2% ± 2.7% (CA + EX); and +0.1% ± 2% (CA + EX + FVLF; P = .047). Lean body mass was largely preserved, even in the control arm (net gain of 452 g ± 2395 g). No differences were observed in other endpoints. Conclusion: Diet and exercise interventions can prevent weight gain and adverse body composition changes, but more research is needed to determine optimally effective interventions that can be implemented during active treatment and that promote adherence.