A Dietary Intervention to Lower Serum Levels of IGF-I in BRCA Mutation Carriers

Abstract

Background: Insulin-like growth factor I (IGF-I) and other markers of insulin resistance (IRm) might influence the penetrance of BRCA gene mutation. In a demonstration project on BRCA mutation carriers we tested the effect of the ‘Mediterranean diet’, with moderate protein restriction, on serum levels of IGF-I and IRm. Methods: BRCA mutation carriers, with or without breast cancer, aged 18–70 years and without metastases were eligible. After the baseline examinations, women were randomized to an active dietary intervention or to a control group. The intervention group attended six full days of life-style intervention activities (cookery classes followed by lunch, sessions of walking for 45 min and nutritional conferences) over the next six months. Results: 213 BRCA mutation carriers completed the six-month study. Women in the intervention group (110) showed major changes in all the parameters under study. They significantly lost weight (p < 0.001), fat mass (p = 0.002), with reduced hip circumference (p = 0.01), triglycerides (p = 0.02) and IGF-I (p = 0.02) compared with controls. They also had a significantly higher levels of insulin-like growth factor-binding protein 3 (IGFI-BP3) (p = 0.03) and a lower IGF-I/IGFI-BP3 ratio (p = 0.04). The reduction of serum levels of IGF-I was significantly associated with the reduction in the consumption of animal products (p = 0.04). Conclusions: Women in the intervention group showed significant improvements in IGF-I and in other IRm that might influence the penetrance of BRCA mutations.

A Mediterranean Dietary Intervention in Female Carriers of BRCA Mutations: Results from an Italian Prospective Randomized Controlled Trial

“…Women often inquire about less invasive risk-reducing options, including dietary and physical activity recommendations, and physicians need to be able to give them evidence-based answers regarding their lifestyle choices, especially for those who opt not to undergo surgery or chemoprevention. The present results and our previous findings [ 10 , 11 , 13 ] indicate that women carriers, if properly instructed, are capable of substantially improving their dietary habits, with significant reduction in their potential modulators of BRCA penetrance. In Germany, the LIBRE study has concluded its feasibility phase (LIBRE-1) confirming the practicability of an intervention involving Mediterranean diet and physical activity in BRCA mutation carriers [ 22 , 23 ].…”

“…We conducted a randomized controlled trial [ 10 , 11 , 12 , 13 , 14 ] of women with deleterious BRCA1 / 2 mutations to test whether a Mediterranean dietary intervention with moderate protein restriction significantly reduces IGF-I and other potential modulators of penetrance.…”

The Impact of Lifestyle Interventions in High-Risk Early Breast Cancer Patients: A Modeling Approach from a Single Institution Experience

“…There was a statistically significant difference between the basal blood glucose and insulin levels at T0 and at T2 ( p = 0.0405 and p < 0.0001 respectively); this is in accordance with the literature: Pasanisi et al conducted a randomized controlled trial evaluating the adhesion to MD and the IGF-1 levels and other markers of insulin resistance in BRCA mutation carriers. In the trial, 203 patients were randomized and those in the experimental arm showed a reduction in IGF-1 levels [ 47 ].…”

The Role of Circulating Adiponectin and SNP276G>T at ADIPOQ Gene in BRCA-mutant Women

“…Study design and patients. The multicenter dietary intervention trial on BRCA-mutant women has been described elsewhere (30,31). Briefly, that study investigated whether an active dietary intervention based on the 'Mediterranean diet' with moderate protein restriction -mainly milk and animal protein, down to 10-12% of total calorie intake -and recommendations for physical activity significantly reduced IGF-I and other markers of insulin resistance.…”

“…In a sample of BRCA-mutant women in a dietary intervention trial to reduce serum levels of IGF-I and other markers of insulin resistance (30,31), we explored the role of the baseline serum levels of adiponectin and leptin and their relation with the SNP276G>T as possible modulators of BRCA penetrance.…”