The impact of expanded access to germline high penetrance genetic testing for women with a new diagnosis of invasive breast cancer or high-grade DCIS

Background Approximately 3% of patients with breast cancer have an inherited pathogenic variant in high-penetrance genes such as BRCA1, BRCA2 or PALB2 . Knowledge of genetic testing result may impact surgery undertaken at the time of index breast cancer treatment. The aim of this study was to evaluate the impact of a positive high penetrance genetic test (HPGT) on surgical decision-making. Methods Females >18 years with a diagnosis of invasive breast cancer or high-grade DCIS who had not had prior BRCA-gene testing were included. In patients with a germline pathogenic variant (GPV), further data were collected on surgical decision-making. Results 576 patients were included. Median time from consent to result was 33 days (IQR 25-45). The rate of GPV was 3.6% (21/576) - 11 BRCA1 (1.9%), 6 BRCA2 (1%), 4 PALB2 (0.7%). 5/21 (23.8%) with GPV would not have been eligible for HPGT on the UK National Health Service R208 pathway. 480/576 (83.3%) underwent primary breast cancer surgery. 121/480 (25.2%) received genetic test results pre-surgery, 359/480 (74.8%) post-surgery. Knowledge of a GPV pre-surgery significantly influenced the initial surgical procedure undertaken (p=0.002). Uptake of subsequent risk-reducing surgery was higher among women with a pre-operative result (100% vs 71.4%), although this difference was not statistically significant (p=0.24). Conclusions Early timing of positive HPGT results significantly influences surgical decision-making and pre-operatively increases uptake of bilateral mastectomy for risk reduction. Expanded access to HPGT in this study identified 24% additional patients with GPV that would not have been eligible for testing on current UK guidelines.