Endocrine Disruptors and Life STILe in Breast Cancer Development

Breast cancer (BC) is the most frequent neoplasm in women; the lifetime probability of developing invasive breast cancer is estimated to be 12.8%. Ovarian cancer (OC) represents the second most common type of gynecologic neoplasm, with an incidence of about 1.5%. A sedentary lifestyle and being overweight seem to play a role in the development of these diseases; an increase in body mass index (BMI) of 5 units is correlated with a 12% increased risk of developing BC and 7-10% increased risk of developing OC. Exposure to environmental toxic factors, such as Cadmium (Cd), has also been found to play a role in the development of BC and OC. Indeed, it has been shown that Cd is involved in the pathogenesis of these neoplasms as it would act as an endocrine disruptor: through binding to the estrogen receptor it would determine its activation thereby promoting cell proliferation. Cd is released into the soil, water and air from natural sources but, most importantly, as a result of industrial processing the processing of nonferrous metals, the production of batteries and paints, the production and application of phosphate-based artificial fertilizers, the use of coal and petroleum, incineration and waste disposal. The general population may be exposed to Cd through: contaminated food and drinking water; cigarette smoking (active and passive), as tobacco leaves accumulate Cd from the soil; and inhalation of dust and fumes, especially for people living near industries that process or emit Cd. At the same time, it is well known that genetic factors are also related to the pathogenesis of BC and OC. In about 20% of patients with triple-negative BC and 20-25% of women with high-grade serous OC, a pathogenetic variant of these genes can be found. In subjects carrying constitutional pathogenetic variants (VPs) in the BRCA1/2 (BRCA1/2m) genes, the absence of repair of damage to the DNA double helix causes its accumulation favoring the development of neoplasms. This results in individuals carrying these variants having a cumulative risk of developing BC of 72% in the case of BRCA1 and 62% in the case of BRCA2. With regard to OC, the risk associated with the presence of VP in the case of BRCA1 is 44% and 17% in the case of BRCA2. These observations are consistent with the hypothesis that genetic risk related to cancer development is modified by environmental or other molecular factors. Several studies have evaluated factors such as lifestyle, overweight, weight gain, and physical inactivity as potential risk elements of BC or OC in BRCA1/2m mutation carriers. The aim of this study is to evaluate the possible interference of environmental factors in the development of BC or OC in women VP carriers of BRCA 1 and BRCA 2