Abstract PO5-08-02: Endocrine Disruptors and Life STILe in Patients Carrying BRCA Pathogenic VAriants With Breast and/or Ovarian CAncer and Women Without Neoplasm: the STILVARCA study

Abstract Background. Pathogenetic variants (PVs) in the BRCA1/2 genes can be found in 20% of patients with breast (BC) or/and ovarian (OC) cancers. In subjects carrying PVs in these genes, the absence of repair of damage to the DNA double helix causes its accumulation favoring neoplasm development. Exposure to environmental pollutants (e.g. Cadmium (Cd), through contaminated food and drinking water, cigarette smoke, dust and fumes inhalation) may play a role in the development of BC and OC. Cd acts as an “endocrine disruptor” through its binding to the estrogen receptor, promoting cell proliferation and increase in mutation rate. Individual lifestyle habits may be associated with cancer onset and progression in these patients. Our aim was to evaluate the interference of environmental factors in the development of BC and/or OC in women carrying PVs in BRCA1/2 genes. Methods. We conducted an observational, multicentric, case-control, retrospective study of patients with PV in BRCA1/2 genes and with BC, OC, or both diagnosed from 2012 to 2020 (Group 1, G1), or without cancer (Group 2, G2). 89 patients (82.4%) developed BC, 17 (15.8%) OC, and 2 (1.8%) experienced both BC and OCs. We collect data about demographics, body mass index (BMI), occupation (divided in employed, educative professions/students, healthcare professions, unemployed/retired and other), type of BRCA mutation (mBRCA), smoking habits (SH), pack/year index, estroprogestinic (EP) use and duration, adherence to Mediterranean diet (with PREDIMED questionnaire) and physical activity (using IPAQ questionnaire). Fisher's exact test and Anova were used to compare patient’s features among the two group. A univariate and multivariable model were fitted to investigate the relationship between adherence to Mediterranean diet, physical activity, Cd exposure through smoking habits (SH), EP use, and cancer development. Results. We evaluated 208 patients, 108 (51.9%) in Group 1 and 100 (48.1%) in Group 2. Table 1 shows ed the features of enrolled patients. 128 (61.5%) had a mBRCA1, 80 (38.5%) a mBRCA2. Analysis of the two groups revealed significative differences in age (47.2 vs 35.6years in G1 and G2, respectively; p .001), SH (38.9% in G1 and 20.0% in G2; p=.002), EP use (36.1% in G1 and 21.0% in G2; p=.021), and occupation (office workers develop cancer more easily, while professions associated with education/students have a lower possibility of developing cancer). No difference was found regarding pack/year index, EP intake duration, adherence to Mediterranean diet, and physical activity. At univariate analysis, predictive factors for cancer incidence were: SH (OR 2.545; 95% CI 1.363 – 4.752 - p=.003); EP use (OR 2.126; 95% CI 1.143 – 3.957 - p=.017); adherence to Mediterranean diet (OR 1.500; 95% CI 1.016 – 2.215 – p=.041). No relationship was found with BMI, occupation and physical activity. At multivariable analysis, SH (OR 2.606; 95% CI 1.370 – 4.959 - p=.004), EP use (2.340; 95% CI 1.224 – 4.474 - p=.010), and adherence to Mediterranean diet (OR 1.544; 95% CI 1-027 – 2.320 – p=.037) were predictive of cancer development. Conclusion. In this preliminary analysis, the risk of development of BC or/and OC in patients with BRCA mutation was influenced by SH, EP use, and adherence to Mediterranean diet. Many environmental factors seem to play a role in the carcinogenesis of mBRCA VP patients. Paths of lifestyle education are highly recommended in BRCAm-carrying women. Table 1. Characteristics of enrolled patients Citation Format: Antonio Franco, Alessandro Rossi, Daniela Andreina Terribile, Emanuela Lucci Cordisco, Ida Paris, Margherita Muratore, Elena Florio, Vanda Salutari, Francesco Pavese, Federica Francesca L'Erario, Antonella Palazzo, Enrico Di Guglielmo, Giulia Borghesiani, Ludovica Cardinali, Elisabetta Ferretti, Giovanni Terrana, Diana Giannarelli, Giovanni Scambia, Silvia Migliaccio, Alessandra Fabi. Endocrine Disruptors and Life STILe in Patients Carrying BRCA Pathogenic VAriants With Breast and/or Ovarian CAncer and Women Without Neoplasm: the STILVARCA study abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-08-02.