RAD51 foci assay (functional HRD test)

What it measures. RAD51 is the protein that carries out homologous recombination repair. When repair is working, cells that have replicated their DNA show nuclear RAD51 foci after damage; when BRCA1, BRCA2, PALB2 or another repair gene is lost, the foci do not form. The assay stains a routine formalin-fixed slide for RAD51 and geminin (a marker of the cells that should be repairing) and reports the share of geminin-positive cells with RAD51 foci. A low score is a functional read-out of homologous recombination deficiency at the moment of the biopsy.

Who should have it. It is being studied in the same settings as genomic HRD tests: high-grade serous ovarian cancer, triple-negative and BRCA-associated breast cancer, and metastatic prostate cancer, where the question is whether a PARP inhibitor or platinum will work. Unlike a genomic scar, which stays behind after resistance has developed, RAD51 foci return when repair is restored, so the assay may also identify patients whose tumours have become resistant.

Evidence. The Vall d'Hebron group showed that a RAD51 score measured in routine samples predicted PARP inhibitor response in patient-derived xenografts beyond BRCA mutation (EMBO Molecular Medicine 2018) and later linked low RAD51 to benefit from platinum in the GeparSixto breast cancer trial. Prospective trials selecting patients on RAD51 are ongoing. The assay is a research and academic laboratory test; no version has regulatory clearance as a companion diagnostic.

What changes. Today, nothing formally: treatment decisions still rest on BRCA sequencing and genomic scar scores. If validated, a low RAD51 score would widen PARP inhibitor use to tumours with no BRCA mutation and a negative scar score, and a high score after progression would argue against continuing them. Cost is that of an immunohistochemistry stain plus specialised scoring, and availability is limited to research centres.