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.

Germline pathogenic variants in the high-penetrance genes BRCA1, BRCA2 and PALB2 identified at breast cancer diagnosis, with an impact on the initial surgical procedure.

About 3% of breast cancer patients carry an inherited pathogenic variant in a high-penetrance gene such as BRCA1, BRCA2 or PALB2. This study offered high-penetrance genetic testing to 576 women over 18 years newly diagnosed with invasive breast cancer or high-grade ductal carcinoma in situ and without prior BRCA testing. Median time from consent to result was 33 days (IQR 25-45) and the germline pathogenic variant rate was 3.6% (21/576): 11 BRCA1 (1.9%), 6 BRCA2 (1%) and 4 PALB2 (0.7%). Five of the 21 carriers (23.8%) would not have been eligible for testing under the UK NHS R208 pathway. Of the 480 patients undergoing primary surgery, 121 (25.2%) received their result preoperatively, and preoperative knowledge significantly influenced the initial procedure performed (P = .002); subsequent uptake of risk-reducing surgery was higher after a preoperative result (100% versus 71.4%) but not significantly so (P = .24).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The figure to remember is five carriers out of twenty-one outside R208 criteria: nearly a quarter of diagnoses escape the current filter, with a median turnaround of 33 days that remains compatible with scheduling surgery. The effect on risk-reducing surgery (100% versus 71.4%), by contrast, does not reach significance in only 21 carriers — the argument rests on the yield of expanded testing, not on that comparison. This is precisely the kind of data that should feed a revision of eligibility criteria rather than a debate about whether to test at all.

Analysis by Dr Thibaut Benquey