Nicoline Hoogerbrugge, Iris Nagtegaal and Marjolijn Lightenberg, theme Tumours of the digestive tract, published in the Journal of the National Cancer Institute that Universal tumor BRCA1/2 testing in all newly diagnosed OC patients is feasible, effective, and appreciated by patients and gynecologists.
BackgroundWomen with epithelial ovarian cancer (OC) have a higher chance to benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) therapy if their tumor has a somatic or hereditary BRCA1/2 pathogenic variant. Current guidelines advise BRCA1/2 genetic predisposition testing for all OC patients, though this does not detect somatic variants. We assessed the feasibility of a workflow for universal tumor DNA BRCA1/2 testing of all newly diagnosed OC patients as a prescreen for PARPi treatment and cancer predisposition testing.
MethodsFormalin-fixed paraffin-embedded tissue was obtained from OC patients in seven hospitals immediately after diagnosis or primary surgery. DNA was extracted, and universal tumor BRCA1/2 testing was then performed in a single site. Diagnostic yield, uptake, referral rates for genetic predisposition testing, and experiences of patients and gynecologists were evaluated.
ResultsTumor BRCA1/2 testing was performed for 315 (77.6%) of the 406 eligible OC samples, of which 305 (96.8%) were successful. In 51 of these patients, pathogenic variants were detected (16.7%). Most patients (88.2%) went on to have a genetic predisposition test. BRCA1/2 pathogenic variants were shown to be hereditary in 56.8% and somatic in 43.2% of patients. Participating gynecologists and patients were overwhelmingly positive about the workflow.
ConclusionsUniversal tumor BRCA1/2 testing in all newly diagnosed OC patients is feasible, effective, and appreciated by patients and gynecologists. Because many variants cannot be detected in DNA from blood, testing tumor DNA as the first step can double the identification rate of patients who stand to benefit most from PARP inhibitors.
Flowchart of the study showing the preferred universal tumor BRCA1/2 workflow on the left side in the dark boxes. n = 0 indicates that the test has been performed and no mutation was present. n = n/a indicates the test has not been performed or the test was unsuccessful and no result could be obtained. OC = epithelial ovarian cancer.
Uptake of universal BRCA1/2 tumor testing and referral for genetic predisposition testing over time. Error bars represent 95% confidence intervals.