Locally Performed HRD Testing for Ovarian Cancer? Yes, We Can!

SIMPLE SUMMARY: Poly (ADP-ribose) polymerase inhibitors (PARPis) have been recently approved by international medicine agencies for the treatment of ovarian cancer patients with either BRCA pathogenic variants or homologous recombination deficiency (HRD), changing the ovarian cancer treatment landscape in both first-line and relapsed disease settings. Thus, assessing HRD is now crucial for patient management, making it a pressing need to offer an alternative to expensive and time-consuming outsourced analysis. The aim of the present study was to demonstrate the feasibility of locally performed HRD testing, using an easy and affordable CE-IVD NGS panel that enabled the analysis of HRD status within 5 days, with perfect concordance with Myriad results. Importantly, this strategy could also be applied in the near future to stratify patients with different tumor types, including breast cancer, pancreatic cancer, and prostatic cancer, thereby expanding the number of patients who could benefit from PARPi treatment. ABSTRACT: Assessment of HRD status is now essential for ovarian cancer patient management. A relevant percentage of high-grade serous carcinoma (HGSC) is characterized by HRD, which is caused by genetic alterations in the homologous recombination repair (HRR) pathway. Recent trials have shown that not only patients with pathogenic/likely pathogenic BRCA variants, but also BRCAwt/HRD patients, are sensitive to PARPis and platinum therapy. The most common HRD test is Myriad MyChoice CDx, but there is a pressing need to offer an alternative to outsourcing analysis, which typically requires high costs and lengthy turnaround times. In order to set up a complete in-house workflow for HRD testing, we analyzed a small cohort of HGSC patients using the CE-IVD AmoyDx HRD Focus Panel and compared our results with Myriad’s. In addition, to further deepen the mechanisms behind HRD, we analyzed the study cohort by using both a custom NGS panel that analyzed 21 HRR-related genes and FISH analysis to determine the copy numbers of PTEN and EMSY. We found complete concordance in HRD status detected by the Amoy and the Myriad assays, supporting the feasibility of internal HRD testing.