Abstract
Simple SummaryUnmet clinical needs in women with deleterious mutations in the BRCA1/2 genes include lifestyle recommendations as adjuvant support and risk-reducing options. Insulin-like growth factor I (IGF-I), body weight and metabolic markers of insulin resistance may affect BRCA penetrance. Therefore, we conducted a multicenter prospective two-armed randomized controlled trial to investigate whether a Mediterranean dietary intervention with moderate protein restriction reduced IGF-I and other metabolic modulators of BRCA penetrance. Out of 502 randomized women with deleterious BRCA1/2 mutations, 416 (216 in the intervention group and 200 in the control group) concluded the six-month dietary intervention and participated in the final examinations. Women in the intervention group significantly lowered serum levels of IGF-I, weight, waist circumference, hip circumference, total cholesterol and triglycerides with respect to the control group. Our findings suggest that a Mediterranean diet with moderate protein restriction is effective in reducing potential modulators of BRCA penetrance.Background: Women carriers of BRCA1/2 mutations face a high lifetime risk (penetrance) of developing breast and/or ovarian cancer. Insulin-like growth factor I (IGF-I), body weight and markers of insulin resistance affect BRCA penetrance. We conducted a multicenter prospective two-armed (1:1) randomized controlled trial (NCT03066856) to investigate whether a Mediterranean dietary intervention with moderate protein restriction reduces IGF-I and other metabolic modulators of BRCA penetrance. Methods: BRCA carriers, with or without a previous cancer, aged 18–70 years and without metastases were randomly assigned to an active dietary intervention group (IG) or to a control group (CG). The primary endpoint of the intervention was the IGF-I reduction. Results: 416 women (216 in the IG and 200 in the CG) concluded the six-month dietary intervention. The IG showed significantly lowered serum levels of IGF-I (−11.3 ng/mL versus −1.3 ng/mL, p = 0.02), weight (−1.5 Kg versus −0.5 Kg, p < 0.001), waist circumference (−2 cm versus −0.7 cm, p = 0.01), hip circumference (−1.6 cm versus −0.5 cm, p = 0.01), total cholesterol (−10.2 mg/dL versus −3.6 mg/dL, p = 0.04) and triglycerides (−8.7 mg/dL versus + 5.5 mg/dL, p = 0.01) with respect to the CG. Conclusions: A Mediterranean dietary intervention with moderate protein restriction is effective in reducing IGF-I and other potential modulators of BRCA penetrance.
Highlights
Women with a deleterious mutation in the BRCA1/2 genes face a lifetime risk of developing breast cancer (BC) in the order of 55%, compared to 12% in the general population, and of developing ovarian cancer (OC) in the order of 16–59% [1,2,3]
The distribution of BRCA1/2 mutations significantly differed in the two groups (p = 0.01) (Table 1)
Compared to the control group (CG), intervention women had a significantly larger improvement in the Mediterranean Diet Adherence Screener (MEDAS) score (Table S2). Findings from this Italian randomized controlled trial show that a dietary intervention based on the Mediterranean diet (MedDiet) with moderate protein restriction is effective in reducing insulin-like growth factor I (IGF-I) and other potential modulators of BRCA penetrance
Summary
Women with a deleterious mutation in the BRCA1/2 genes face a lifetime risk (penetrance) of developing breast cancer (BC) in the order of 55%, compared to 12% in the general population, and of developing ovarian cancer (OC) in the order of 16–59% [1,2,3]. The lifetime risk of developing OC was 44% (95% CI, 36–55%) for BRCA1 and 17% (95% CI, 11–25%) for BRCA2 mutation carriers [4]. Obesity may affect BRCA penetrance through a number of mechanisms, including insulin resistance and insulin-like growth factor I (IGF-I) regulation. Women with BRCA1/2 mutations more frequently develop type-2 diabetes after a BC diagnosis [7] compared with carriers without cancer. Women carriers of BRCA1/2 mutations face a high lifetime risk (penetrance) of developing breast and/or ovarian cancer. Insulin-like growth factor I (IGF-I), body weight and markers of insulin resistance affect BRCA penetrance. We conducted a multicenter prospective two-armed (1:1) randomized controlled trial (NCT03066856) to investigate whether a Mediterranean dietary intervention with moderate protein restriction reduces IGF-I and other metabolic modulators of BRCA penetrance.
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