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.

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. Females >18 years diagnosed with invasive breast cancer or high-grade Ductal carcinoma in situ (DCIS) without prior BRCA-gene testing were included. In patients with a germline pathogenic variant (GPV) further data on surgical decision-making were collected. Five hundred seventy-six patients were included. Median time from consent to result was 33 days (inter-quartile range 25-45). GPV rate was 3.6% (21/576): 11 BRCA1 (1.9%), 6 BRCA2 (1%), 4 PALB2 (0.7%). Five (23.8%) of 21 patients with GPV would not have been eligible for HPGT on the UK National Health Service R208 pathway. Four hundred eighty (83.3%) of the 576 patients underwent primary breast cancer surgery; 121 (25.2%) of 480 patients received results pre-operatively, 359 (74.8%) post-operatively. Pre-operative GPV knowledge significantly influenced the initial surgical procedure undertaken (P = .002). Uptake of subsequent risk-reducing surgery was higher with a preoperative result (100% vs. 71.4%), although this difference was not statistically significant (P = .24). Early timing of positive HPGT results significantly influences surgical decision-making and increases pre-operative uptake of bilateral risk-reducing mastectomy. Expanded HPGT access in this study identified 24% additional patients with GPV who would not have met current UK testing criteria.