Eleonora Bruno1, Andreina Oliverio1, Angelo Paradiso2, Antonella Daniele3, Stefania Tommasi4, Daniela A Terribile5, Alessio Filippone6, Maria Digennaro2, Brunella Pilato4, Katia Danza4, Donatella Guarino6, Cristina Rossi7, Maria Maddalena Rossi7, Elisabetta Venturelli1, Marta Giussani8, Bernard Peissel9, Patrizia Pasanisi10. 1. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. 2. Experimental Oncology, Center for Study of Heredo-Familial Tumors, IRCCS Istituto Tumori "Giovanni Paolo II" Bari, Bari, Italy. 3. Experimental Oncology and Biobank Management Unit, IRCCS Istituto Tumori "Giovanni Paolo II" Bari, Bari, Italy. 4. Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumori "Giovanni Paolo II" Bari, Bari, Italy. 5. Department of Women Health Area, Università Cattolica, Rome, Italy; Department of Women and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 6. Department of Women Health Area, Università Cattolica, Rome, Italy. 7. Department of Women and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 8. Unit of Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. 9. Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. 10. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. Electronic address: patrizia.pasanisi@istitutotumori.mi.it.
Abstract
BACKGROUND: Women with deleterious mutations in BRCA1/2 have a high lifetime penetrance of developing breast cancer and/or ovarian cancer. Genetic and/or environmental factors may influence BRCA penetrance, and identifying modifiable exposures might be valuable for prevention. PATIENTS AND METHODS: We implemented a multicenter prospective 2-arm (1:1) randomized controlled trial to investigate whether a Mediterranean dietary intervention with moderate protein restriction would reduce potential modulators of BRCA penetrance such as insulin-like growth factor 1 (IGF-1), body weight, and metabolic risk factors. We studied the baseline characteristics of women with BRCA-positive disease who joined the trial cohort, focusing on the relationships between selected lifestyle exposures, metabolic/anthropometric parameters, and BRCA-related cancer. RESULTS: A total of 502 women (304 with a previous diagnosis of breast cancer and/or ovarian cancer and 198 unaffected) with deleterious BRCA mutations, with or without a previous cancer, aged 18 to 70 years and without metastases were included. Late age at menarche and pregnancy were negatively associated with BRCA-related cancer, especially in women with BRCA1-positive disease. Higher fat mass and the presence of 4 or 5 metabolic risk factors were significantly associated with BRCA-related cancer (hazard ratio, 1.87, 95% confidence interval, 1.21-2.88; and hazard ratio, 1.87, 95% confidence interval, 1.11-3.19, respectively), with greater effect in BRCA2-positive women. CONCLUSIONS: Our findings confirm previous observations about reproductive factors in women with BRCA disease and suggest a potential impact of metabolic factors in BRCA-related cancer. The prospective follow-up of the trial cohort will enable us to study the environmental modulators of BRCA penetrance and their impact in relation to the history of BRCA-related cancer. [ClinicalTrials.gov NCT03066856].
BACKGROUND: Women with deleterious mutations in BRCA1/2 have a high lifetime penetrance of developing breast cancer and/or ovarian cancer. Genetic and/or environmental factors may influence BRCA penetrance, and identifying modifiable exposures might be valuable for prevention. PATIENTS AND METHODS: We implemented a multicenter prospective 2-arm (1:1) randomized controlled trial to investigate whether a Mediterranean dietary intervention with moderate protein restriction would reduce potential modulators of BRCA penetrance such as insulin-like growth factor 1 (IGF-1), body weight, and metabolic risk factors. We studied the baseline characteristics of women with BRCA-positive disease who joined the trial cohort, focusing on the relationships between selected lifestyle exposures, metabolic/anthropometric parameters, and BRCA-related cancer. RESULTS: A total of 502 women (304 with a previous diagnosis of breast cancer and/or ovarian cancer and 198 unaffected) with deleterious BRCA mutations, with or without a previous cancer, aged 18 to 70 years and without metastases were included. Late age at menarche and pregnancy were negatively associated with BRCA-related cancer, especially in women with BRCA1-positive disease. Higher fat mass and the presence of 4 or 5 metabolic risk factors were significantly associated with BRCA-related cancer (hazard ratio, 1.87, 95% confidence interval, 1.21-2.88; and hazard ratio, 1.87, 95% confidence interval, 1.11-3.19, respectively), with greater effect in BRCA2-positive women. CONCLUSIONS: Our findings confirm previous observations about reproductive factors in women with BRCA disease and suggest a potential impact of metabolic factors in BRCA-related cancer. The prospective follow-up of the trial cohort will enable us to study the environmental modulators of BRCA penetrance and their impact in relation to the history of BRCA-related cancer. [ClinicalTrials.gov NCT03066856].