Germline BRCA1/2 testing: Trend in Tan Tock Seng Hospital Singapore

Abstract Background Tan Tock Seng Hospital (TTSH) Cancer Genetics and Genomics Clinic (CGGC) was set up by the Personalised Medicine Services (PMS) and Department of Medical Oncology (DMO) in December 2017 to provide genetic counselling service for inherited cancer syndromes diagnosis, risk assessment and treatment recommendation. Patient’s affordability for genetic testing was noted as one of the greatest challenges. In January 2019, a diagnostic access program was established between AstraZeneca Singapore and PMS to reduce cost barriers for patients who fulfil clinical guidelines for BRCA1/2 testing. Methods This is a retrospective study of BRCA1/2 test utilisation by patients who were seen at CGGC. The oncologist made the decision on the use of a targeted BRCA1/2 or multi-gene panels for genetic testing. The objectives of this study were to examine the clinical utilisation of BRCA1/2 testing, and to determine the proportion of patients who benefited from the access program. Results To date, 101 out of 140 patients were seen at CGGC for BRCA-related testing. Patients’ referral are mainly from DMO and Breast Clinic. With the increased use of PARP inhibitors for germline BRCA-mutated cancers, the number of patients referred to CGGC has increased 20% per month. The percentage of breast, prostate, pancreatic and ovarian cancer patients seen are 75%, 11%, 10% and 5%, respectively. The introduction of the access program has greatly increased the testing rate from 50% to 85%. The positive detection rate was 11%. Among 65 that underwent testing, 7 patients were tested BRCA1/2 mutation positive, which resulted in protein truncation or disruption. However, the take up rate for carrier testing was low, probably due to fear of being affected and insurance discrimination. The variant of unknown significance rate for BRCA1/2 was 14%. Among the 75% tested BRCA1/2 negative, a genetic cause of their cancer cannot be ruled out. For example, 2 BRCA1/2 negative breast cancer patients were tested positive in CHEK2 and PALB2 genes. Conclusions CGGC service in TTSH is growing rapidly and has closed an important gap in our patient treatment journey. The sponsorship by AstraZeneca has greatly benefited our patients who might be at risk of inherited cancer syndromes and would potentially benefit from PARP inhibitors treatment. Legal entity responsible for the study Tan Tock Seng Hospital. Funding AstraZeneca Singapore. Disclosure All authors have declared no conflicts of interest.