Abstract PS4-46: Homologous recombination deficiency score predicts patient characteristics and outcomes of triple negative breast cancer in China

BackgroundPrevious studies found homologous recombination deficiency (HRD) score could predict response to platinum-containing neoadjuvant chemotherapy in patients with triple negative breast cancer (TNBC), but its predictive effects of adjuvant chemotherapy is unexplored. Methods We developed the 3DMed-HRD algorithm, which combines loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI) and large-scale state transition score (LST) to characterize genomic instability using over 10000 SNPs, adjusted by tumor ploidy and purity. HRD positive is defined by deleterious mutation in BRCA1/2 or HRD score above the threshold (cut-off ≥30). Tumor samples were retrospectively obtained from 149 TNBC patients who received platinum-based (paclitaxel and cisplatin, TP) or platinum-free (cyclophosphamide and adriamycin, EC) adjuvant chemotherapy after surgery. All patients underwent the 3DMed-HRD testing. ResultsIn 25.5% (38/149) of TNBC patients deleterious germline or somatic mutation in BRCA 1/2 was detected. HRD results were available for all patients and 81of the 149 patients (54.4%) were defined as HRD positive. HRD-positive patients had younger age at diagnosis (median 46.7 years vs 51.5 years, P=0.002), higher differentiated (59.8% vs 39.5%; p=0.037), lower N-stage (55.7% vs 33.3%; p=0.006) and more common at high expression of Ki67 (64.7% vs 39.0%; p=0.015). In TP treatment group, patients with HRD positive tumors had a lower 5-year recurrence rate although the difference was not statistically significant (8.82% vs 16.1%; p=0.463). Patients in EC treatment cohort, 5-year recurrence rate was comparable between HRD positive and negative subgroups (15.4% vs 13.3%; p=1.0). In the 81 patients in HRD-positive cohort, patients in TP treatment group showed a numerical lower 5-year recurrence rates compared with patients in EC treatment group (8.82% vs 15.4%; p=0.489). Conclusions54.5% patients were characterized as HRD positive in TNBC patients in our cohort. HRD was associated with clinicopathologic characteristics. Our results suggested that HRD status mightguide chemotherapy treatment decisions. Prospective validation with larger sample size is needed. Citation Format: Xue Wang, Feng Du, Jian Yue, Yiran Si, Lina Cui, Peng Yuan. Homologous recombination deficiency score predicts patient characteristics and outcomes of triple negative breast cancer in China [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-46.