BRCAness

BRCAness is a term used in oncology to describe tumors that exhibit a BRCA1/BRCA2-like impairment of the homologous recombination DNA repair pathway, even if BRCA genes themselves are not mutated. This HR deficiency leads to genomic instability and a characteristic sensitivity to DNA-damaging agents such as platinum chemotherapy and poly(ADP-ribose) polymerase (PARP) inhibitors, and it underpins a subset of breast, ovarian, pancreatic, and other cancers.

The basis is heterogeneous. It includes BRCA1/BRCA2 alterations, but also mutations in PALB2, RAD51 family, BRIP1, RAD51C/D, and epigenetic silencing like BRCA1 methylation. The HRD state may be detected by genomic scar patterns reflecting HR deficiency.

Detection and interpretation: Genomic scar assays measure HRD patterns such as LOH, telomeric imbalance, and large-scale transitions; composite HRD scores are used in some clinics. BRCA1/2 testing remains standard; broader HRD testing lacks universal standards.

Clinical implications: BRCAness predicts response to PARP inhibitors (olaparib, niraparib, rucaparib) and often to platinum therapy, particularly in high-grade serous ovarian cancer and BRCA1/2-mutant or HRD-defined breast cancers; it guides treatment and is being studied in other tumors.

Limitations: Not all HRD tumors respond; testing methods and cutoffs vary. Resistance can arise through reversion mutations restoring HR. Ongoing work aims to refine HRD detection and optimize combination therapies.