The effects of Mediterranean diet, physical activity, and vitamin D on breast cancer recurrence and cardiometabolic health: A multicenter randomized trial.

511 Background: Low quality diets and physical inactivity are two modifiable lifestyle factors that together with vitamin D deficiency have been associated with unfavorable breast cancer (BC) outcomes and cardiometabolic health. We therefore tested the effect of a lifestyle program on BC recurrence and cardiometabolic risk factors on a background of vitamin D sufficiency. Methods: Women aged 30-74 years were enrolled in a phase III trial (NCT02786875) within 12 months of their primary BC diagnosis (stages I-III) in 7 oncologic centres in Italy. Consenting participants were randomized to one of two lifestyle treatments lasting 33 months: 1) positive control (n = 249), standard advice on a Mediterranean diet (MedDiet) and avoidance of sedentary behavior; 2) intervention (n = 243), high intensity advice on low-glycemic index MedDiet and 30-minute additional daily brisk walking. Oral vitamin D3 was administered throughout. Data were collected quarterly on health status, anthropometry, 7-day food records, daily steps, serum 25(OH)D concentrations and metabolic syndrome parameters. The primary outcome was BC recurrence (intention to treat analysis) at 33 months, with cardiometabolic risk factors as secondary outcomes. Hazard ratios (HR) and 95% confidence intervals (CI) for BC recurrence were computed using Cox proportional hazards models adjusted for recruitment center. One-year changes in treatment variables and cardiometabolic risk factors were tested by paired Student’s t-test within each treatment arm and by analysis of covariance between treatment arms, adjusted for baseline values. Results: Approximately 58% of patients were aged ≥50 years, 94% were postmenopausal, 86% had stages I-IIB and 75% hormone-positive BC. A total of 37 recurrences were observed with no differences between arms (HR = 0.94, 95%CI: 0.49-1.79). Independently of randomization arm, women with hormone-positive BC who were more adherent to the intervention program (41%), showed 76% lower risk of BC recurrence (HR = 0.24, 95% CI: 0.06-0.95). Weight loss of 3 kg, representing a 4.2% drop of initial body weight, was significantly greater in the test arm compared to 1.7 kg or 2.4% in the control arm (p = 0.0034). This translated in reductions of body mass index from 27.5±5.7 to 26.3±5.4 kg/m 2 in the intervention arm and from 27.2±5.1 to 26.6±5.1 kg/m 2 in controls (p = 0.0032). The presence of metabolic syndrome dropped by 65% in the intervention arm and 34% in controls (p = 0.008). The probability of metabolic syndrome remission was 2.5-fold higher in the intervention arm. Conclusions: A safe and low-cost lifestyle program with low-glycemic index MedDiet, daily brisk walking and oral vitamin D supplementation resulted in weight loss, reduced metabolic syndrome prevalence and was significantly associated with lower recurrences in women with hormone-positive BC. Clinical trial information: NCT02786875 .