HRD stands for homologous recombination deficiency. It is a biological phenotype characterized by a cell’s inability to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway.
Key details regarding HRD from the sources include:
- Clinical Significance: Tumors with HRD are often more sensitive to platinum-based chemotherapy and PARP inhibitors (such as olaparib, rucaparib, and niraparib). Assessment of HRD status is used to guide maintenance therapy strategies in advanced ovarian cancer.
- Measurement and Testing: HRD is typically determined by identifying deleterious BRCA1 or BRCA2 mutations (germline or somatic) and/or by assessing “genomic instability”.
- HRD Score: Commercial tests, such as the Myriad myChoice CDx, calculate an HRD score by assessing three biomarkers of genomic instability: loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST).
- Thresholds: While definitions can vary by clinical trial, a score of > 42 is frequently reported as “positive” or HRD-deficient. Other sources mention an HRD score threshold of > 16 in specific contexts.
- Maintenance Therapy: For example, in the PAOLA-1 trial, the combination of bevacizumab and olaparib showed a significant progression-free survival benefit in patients who were HRD-positive, regardless of their BRCA mutation status.
Synonyms
HRD