Implementing HRD Testing in Routine Clinical Practice on Patients with Primary High-Grade Advanced Ovarian Cancer

Testing for a homologous recombination deficiency (HRD) in primary high-grade ovarian cancer is crucial for recommending the appropriate therapy. Patients with a BRCA germline mutation are defined as harboring an HRD deficiency. However, there is a group of approximately 20% of patients without a BRCA mutation which harbor an HRD deficiency based on tumor genomic analyses. In the current research, we wanted to share the experience of a high-volume tertiary cancer center with implementing central HRD testing-in another institution-to reduce doubts about logistic issues and to the highlight critical aspects that hinder HRD testing. We showed that the results of HRD testing became available in a timely manner for the therapy decision. However, it was important to obtain as much tumor tissue as possible during the first diagnosis-before any other intervention-as the tumor quantity and quality were critical for HRD testing. Additional BRCA germline testing further reduced the failures of HRD testing and should additionally be routinely conducted. The chemotherapy backbone for patients with high-grade advanced epithelial ovarian cancer (HG-AOC) is carboplatin and paclitaxel followed by a maintenance therapy either with bevacizumab, with a PARP inhibitor, or with a combination of both, which is defined by the presence of a homologous recombination deficiency (HRD) and by the BRCA1/2 status. This study included patients with a primary diagnosis of HG-AOC treated between December 2019 and December 2021. The HRD status was measured using the Myriad myChoice((R)) test on all the patients with an indication for tumor HRD testing. Germline testing was conducted on all the patients using the TruRisk((R)) panel as recommended by the national guidelines. HRD testing was requested for 190 patients, and, for 163 patients (85.8%), an HRD test result was available. An HRD test result could not be reported in 27 patients due to an insufficient tumor yield. The median time that it took to receive the HRD test results was 37 days (range of 8-97). In total, an HRD was present in 44.7% (73/163) of the patients based on a GIS >= 42 in 42.9% of the patients and based on a tumor BRCA1/2 mutation in 3 cases (all with a GIS < 42). The germline testing results were available for 148 patients, and, in 18 patients (12.2%), a deleterious germline mutation was detected. Of the 27 patients without sufficient HRD testing, BRCA1/2 germline testing results were available for 19 patients (70.4%), and a deleterious germline mutation was detected in 2 patients (7.4%). The implementation of HRD testing is feasible, and the results become available for treatment decisions in a timely manner for most patients. The prerequisite for HRD testing with the Myriad myChoice((R)) test is a sufficient amount of tumor tissue. The cotesting of HRD and BRCA1/2 germline testing should be aimed for in order to enable optimal and timely treatment decisions on maintenance therapy as well as to test patients on whom the HRD test will not be evaluable.