Lifestyle Characteristics in Women Carriers of BRCA Mutations: Results From an Italian Trial Cohort

Published:November 10, 2020DOI:



      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.


      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.


      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. [ NCT03066856]


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        • Lalloo F.
        • Evans D.G.
        Familial breast cancer.
        Clin Genet. 2012; 82: 105-114
        • Antoniou A.
        • Pharoah P.D.
        • Narod S.
        • et al.
        Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies.
        Am J Hum Genet. 2003; 72: 1117-1130
        • Berrino J.
        • Berrino F.
        • Francisci S.
        • et al.
        Estimate of the penetrance of BRCA mutation and the COS software for the assessment of BRCA mutation probability.
        Fam Cancer. 2015; 14: 117-128
        • Chen S.
        • Parmigiani G.
        Meta-analysis of BRCA1 and BRCA2 penetrance.
        J Clin Oncol. 2007; 25: 1329-1333
        • Mavaddat N.
        • Peock S.
        • Frost D.
        • et al.
        Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE.
        J Natl Cancer Inst. 2013; 105: 812-822
        • Antoniou A.C.
        • Beesley J.
        • McGuffog L.
        • et al.
        Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction.
        Cancer Res. 2010; 70: 9742-9754
        • Rebbeck T.R.
        • Mitra N.
        • Domchek S.M.
        • et al.
        Modification of BRCA1-associated breast and ovarian cancer risk by BRCA1-interacting genes.
        Cancer Res. 2011; 71: 5792-5805
        • Tryggvadottir L.
        • Sigvaldason H.
        • Olafsdottir G.H.
        • et al.
        Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000.
        J Natl Cancer Inst. 2006; 98: 116-122
        • Bruno E.
        • Manoukian S.
        • Venturelli E.
        • et al.
        Adherence to Mediterranean diet and metabolic syndrome in BRCA mutation carriers.
        Integr Cancer Ther. 2018; 17: 153-160
        • Pasanisi P.
        • Bruno E.
        • Manoukian S.
        • Berrino F.
        A randomized controlled trial of diet and physical activity in BRCA mutation carriers.
        Fam Cancer. 2014; 13: 181-187
        • Pasanisi P.
        • Bruno E.
        • Venturelli E.
        • et al.
        A dietary intervention to lower serum levels of IGF-I in BRCA mutation carriers.
        Cancers (Basel). 2018; 10: 309
        • Schroder H.
        • Fito M.
        • Estruch R.
        • et al.
        A short screener is valid for assessing Mediterranean diet adherence among older Spanish men and women.
        J Nutr. 2011; 141: 1140-1145
        • Alberti K.G.
        • Zimmet P.
        • Shaw J.
        The metabolic syndrome—a new worldwide definition.
        Lancet. 2005; 366: 1059-1062
        • Haftenberger M.
        • Lahmann P.H.
        • Panico S.
        • et al.
        Overweight, obesity and fat distribution in 50- to 64-year-old participants in the European Prospective Investigation into Cancer and Nutrition (EPIC).
        Public Health Nutr. 2002; 5: 1147-1162
        • Pan H.
        • He Z.
        • Ling L.
        • et al.
        Reproductive factors and breast cancer risk among BRCA1 or BRCA2 mutation carriers: results from ten studies.
        Cancer Epidemiol. 2014; 38: 1-8
        • Park B.
        • Hopper J.L.
        • Win A.K.
        • et al.
        Reproductive factors as risk modifiers of breast cancer in BRCA mutation carriers and high-risk non-carriers.
        Oncotarget. 2017; 8: 102110-102118
        • Kotsopoulos J.
        • Gronwald J.
        • Lynch H.T.
        • et al.
        Age at first full-term birth and breast cancer risk in BRCA1 and BRCA2 mutation carriers.
        Breast Cancer Res Treat. 2018; 171: 421-426
        • Russo J.
        • Russo I.H.
        Cellular basis of breast cancer susceptibility.
        Oncol Res. 1999; 11: 169-178
        • Russo J.
        • Lynch H.
        • Russo I.H.
        Mammary gland architecture as a determining factor in the susceptibility of the human breast to cancer.
        Breast J. 2001; 7: 278-291
        • Di L.J.
        • Fernandez A.G.
        • De S.A.
        • Longo D.L.
        • Gardner K.
        Transcriptional regulation of BRCA1 expression by a metabolic switch.
        Nat Struct Mol Biol. 2010; 17: 1406-1413
        • Esposito K.
        • Chiodini P.
        • Capuano A.
        • et al.
        Metabolic syndrome and postmenopausal breast cancer: systematic review and meta-analysis.
        Menopause. 2013; 20: 1301-1309
        • Key T.J.
        • Appleby P.N.
        • Reeves G.K.
        • Roddam A.W.
        Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies.
        Lancet Oncol. 2010; 11: 530-542
        • Pasanisi P.
        • Villarini A.
        • Raimondi M.
        • Bruno E.
        • Gargano G.
        • Berrino F.
        Nutritional advice to breast cancer survivors.
        Support Care Cancer. 2010; 18: 29-33
        • Iyengar N.M.
        • Arthur R.
        • Manson J.E.
        • et al.
        Association of body fat and risk of breast cancer in postmenopausal women with normal body mass index: a secondary analysis of a randomized clinical trial and observational study.
        JAMA Oncol. 2019; 5: 155-163
        • Shu X.
        • Wu L.
        • Khankari N.K.
        • et al.
        Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis.
        Int J Epidemiol. 2019; 48: 795-806
        • Pasanisi P.
        • Bruno E.
        • Venturelli E.
        • et al.
        Serum levels of IGF-I and BRCA penetrance: a case control study in breast cancer families.
        Fam Cancer. 2011; 10: 521-528
        • Hirschey M.D.
        • DeBerardinis R.J.
        • Diehl A.M.
        • et al.
        Dysregulated metabolism contributes to oncogenesis.
        Semin Cancer Biol. 2015; 35: S129-S150