315P High-penetrance breast and/or ovarian cancer susceptibility genes in Filipinos

Abstract

Breast cancer is the most common cancer seen in women worldwide. In the Philippines, 24,798 cases of breast cancer were diagnosed in 2018, making up 17.6% of 141,021 newly diagnosed cases of cancer in the country. Genetic counseling and testing for hereditary cancers is a relatively new undertaking for medical oncologists in the Philippines. Previous studies show that prevalence of BRCA mutations in Filipinos is 5.1% to 6.8%, which is consistent with data found in the Asian population. However, no studies have yet been done looking at multigene panel testing for Filipino patients who meet the testing criteria for high-penetrance breast and/or ovarian cancer susceptibility genes. From September 2019 to May 2020, we did multigene panel testing (Invitae Multi-Cancer Panel) for patients who met the testing criteria for high-penetrance breast and/or ovarian cancer susceptibility genes (NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020 – December 4, 2019). We tested 24 patients (23 females, 1 male; 29-81 years old), including 14 with breast cancer, 4 with ovarian cancer, 1 with both breast and ovarian cancer, 2 with pancreatic cancer, and 3 with no cancer but strong family history. Among the 24 patients tested, none had pathogenic BRCA1/2 mutations. However, one (4%) had a pathogenic PALB2 mutation (c.757_758del (p.Leu253Ilefs*3)), fourteen (58%) had one or more variants of uncertain significance (ALK, ATM, BARD1, BRCA2, CDKN1B, EGFR, KIT, MSH2, MSH6, MUTYH, NF1, NTHL1, POLE, RAD51D, RECQL4, SDHA, SDHB, SMARCA4, SMARCB1, TSC1), and nine (38%) had negative results. As cancer genetics becomes more mainstream, use of multigene panels has been increasing, and cost of testing has been decreasing, making this more accessible to the average Filipino cancer patient. This is the first study to document the presence of other high-penetrance breast and/or ovarian cancer susceptibility genes in Filipinos. However, more research has to be done as we still do not know all the genes that may cause hereditary breast cancer and use of multigene panels increases the rates of detecting variants of uncertain significance and other incidental findings.