Breast cancer, the most diagnosed cancer in women, results from combined effects of genetic and environmental factors. Modification of DNA repair system activity and cell inability to restore damaged DNA determine the initiation of carcinogenesis. Mutated genes of the BRCA family lead to the formation of dysfunctional DNA repair proteins that are unable to perform the function. Non-repaired DNA initiates genetic instability with an increased risk of the oncogenic transformation of non-tumorigenic cells into malignant initiating cells. This suggests that personalized prevention strategies should be considered based on individual genetic profiles. An increasing amount of research indicates that genetic factors can influence the relationship between diet, exercise, obesity, and environmental factors and the risk of breast cancer. The genetic approach to secondary breast cancer prevention involves understanding how genetic factors, such as mutations in genes like BRCA, interact with environmental factors to increase the risk of breast cancer. By identifying individuals with specific genetic profiles that predispose them to a higher risk of developing breast cancer, targeted preventive strategies can be implemented. We have shown a high frequency of mutant alleles and 6-fold higher risk of mutation formation of the BRCA genes in residents of the observation zone where petrochemical production enterprises are concentrated. Studying gene–environment interaction offers the opportunity to obtain new knowledge on several aspects of breast cancer etiology and it may help to improve preventive strategies for personalized health care. These include behavior modification for high-risk subjects (primary prevention), early detection and extensive monitoring of genetically susceptible subjects and noninvasive treatment of early stage cancer cases (secondary prevention), and finally prophylactic and therapeutic intervention to slow diseases progression (tertiary prevention).