Homologous recombination deficiency (HRD) represents a pivotal concept in oncology, characterized by a functional loss in the homologous recombination repair (HRR) pathway. Essential for repairing DNA double-strand breaks (DSBs), the most severe forms of genetic damage, HRD arises from mutations in genes like BRCA1, BRCA2, and others.1 These mutations, whether inherited (germline) or acquired (somatic), impede the cell’s ability to repair DSBs. The concept of “BRCAness” extends this definition, describing tumours with similar molecular characteristics to BRCA mutation-induced HRD, caused by defects in other HRR pathway genes such as ATM, ATR, or RAD51c.
Currently, it’s estimated that a notable percentage of cancer patients, particularly those with triple-negative breast cancer (TNBC) and HER2-negative breast cancers, exhibit some form of HRD. However, due to the restricted criteria of current testing methodologies, a substantial number of these patients might be missed. This underdiagnosis means that many individuals who could benefit from targeted therapies like PARP inhibitors are not receiving them. Thus, HRD testing becomes instrumental in guiding treatment decisions and tailoring personalized cancer therapy strategies.
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