Combined Homologous Recombination Deficiency (HRD) scores and response to neoadjuvant platinum-based chemotherapy in triple-negative and/or BRCA1/2 mutation-associated breast cancer.

1018 Background: The HRD-LOH (loss of heterozygosity) score is significantly associated with favorable response to neoadjuvant platinum-based therapy in PrECOG 0105. We set out here to assess the combined HRD score, an unweighted sum of LOH, telomeric allelic imbalance (TAI) and large-scale state transitions (LST) scores. In combination, these measures are a more robust predictor of HR deficiency than the individual components. Methods: The HRD threshold was previously established by analyzing scores in a training cohort of 497 breast and 561 ovarian chemotherapy naive tumors with known defects in HR, and defining a cut-off with 95% sensitivity to detect those HR deficient tumors. This threshold, along with BRCA1/2 tumor mutation data, was used to predefine tumors from the PrECOG 0105 cohort (N = 93; 72 with molecular data) as either HR deficient (HRD score ≥ the threshold OR a tumor BRCA1/2 mutation) or HR non-deficient (HRD score < the threshold and no tumor BRCA1/2 mutation). Results: In univariate ana...