HRD genomic scar scores (GIS, LOH, HRDetect)

What they measure. When homologous recombination fails, the genome accumulates a characteristic pattern of large deletions, loss of heterozygosity and rearranged chromosome ends. Scar scores count these footprints from tumour sequencing. The Myriad myChoice genomic instability score adds up loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions; FoundationOne CDx reports a genome-wide loss of heterozygosity percentage; HRDetect (Nature Medicine 2017) weighs mutational signatures, including signature 3 and small deletions with microhomology, from whole-genome data; and academic and regional laboratories run their own versions on targeted panels or low-pass genomes. All are reported with a threshold that calls the tumour HRD positive or negative.

Who should have it. Guidelines recommend tumour HRD testing at diagnosis of advanced high-grade ovarian cancer to decide maintenance treatment. In PRIMA (niraparib) and PAOLA-1 (olaparib plus bevacizumab), the benefit of PARP inhibitor maintenance was concentrated in HRD-positive tumours, and the drug labels in Europe are written around that status. Use in breast, prostate and pancreatic cancer is investigational; there the decision still rests on BRCA and related gene mutations.

What changes. HRD positive without a BRCA mutation opens PARP inhibitor maintenance; HRD negative usually means bevacizumab alone or observation, though a share of HRD-negative patients still respond. The scar is permanent: it stays after the tumour restores repair and becomes resistant, so a positive score in relapsed disease overstates current sensitivity, which is where functional assays such as the RAD51 test aim to help. The thresholds differ between assays, so a tumour can be positive on one test and negative on another.

Regulatory status and cost. myChoice CDx is FDA approved as a companion diagnostic; several kit-based European tests are CE marked. The test is a tumour-tissue sequencing assay with a turnaround of two to four weeks, priced in the range of a comprehensive genomic panel, and covered by many health systems for ovarian cancer.