Germline Mutations in Latin American Women With Breast Cancer

PURPOSE Breast cancer is the most common form of cancer among women in Latin America. Limited health care access, late-stage diagnosis, and lack of knowledge on the mutation profile of cancer susceptibility genes in low- and middle-income country populations lead to higher mortality rates. To address this health disparity, this study analyzes the breast cancer mutation profile of women from Mexico and Guatemala. Results from this study can be used to improve breast cancer screenings in these countries and for Latin American women living in the United States. METHODS Genomic and clinical data of women with breast tumors were obtained at the Instituto Nacional de Salud Publica in Mexico and Instituto Nacional de Cancerologia in Guatemala. Mutations in known breast cancer susceptibility genes were identified using targeted sequencing and were validated by manual review in the Integrative Genomics Viewer and pathogenicity determined using online databases (ClinVar and Varsome). Finally, variants were compared with corresponding clinical data for population-wide trends. RESULTS The Mexico study identified 14% of cases with pathogenic mutations in a sample of 201 patients and the Guatemala study contained 11% pathogenic mutations in 673 patients. The most frequently mutated genes for both populations were BRCA1, BRCA2, PALB2, and TP53, with BRCA1/2 mutations accounting for 7% to 10% of all variants. Patients with pathogenic mutations were found to have a significantly younger age of onset than patients without mutations, and a family history of breast cancer was pronounced in patients with pathogenic mutations. CONCLUSION The results of this study increase our understanding of the molecular and pathologic characteristics of breast cancer in Latin American women. This list of pathogenic variants and their clinical characteristics should be used to inform cancer screening, diagnosis, and treatment in the United States and abroad.