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Given the recent FDA-approval of two PARP inhibitors for prostate cancer, HRD score analysis could help to refine treatment selection. J Clin Oncol 2019 37:abstract 202.The homologous recombination deficiency (HRD) score integrates three DNA-based measures of genomic instability, and has been understudied in prostate cancer. Phase II study of niraparib in patients with metastatic castration-resistant prostate cancer (mCRPC) and biallelic DNA-repair gene defects (DRD): Preliminary results of GALAHAD. Smith MR, Sandhu SK, Kelly WK, Scher HI, Efstathiou E, Lara P, et al. Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study. N Engl J Med 2020 382:2091–102.Ībida W, Campbell D, Patnaik A, Shapiro JD, Sautois B, Vogelzang NJ, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2015 373:1697–708.ĭe Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. Prospective Comprehensive Genomic Profiling of Primary and Metastatic Prostate Tumors. Germline BRCA2-altered cases have significantly higher HRD scores than germline ATM-altered or CHEK2-altered cases, consistent with the lower efficacy of PARP inhibitors among the latter.Ĭhung JH, Dewal N, Sokol E, Mathew P, Whitehead R, Millis SZ, et al. We conclude that HRD scores are low in primary prostate cancer and higher in cases with germline BRCA2 or somatic TP53 mutations. Finally, among eight BRCA2-altered patients who received olaparib, progression-free survival trended longer in those with HRD scores above versus below the median (14.9 vs. 11 p = 0.015) this finding was confirmed in the PROGENE cohort (24 vs.

In the absence of HR gene mutations, the median HRD score was unexpectedly higher among prostate cancers with TP53 mutations versus those without (17 vs. For TCGA tumors without underlying HR pathway mutations, the median HRD score was 11, significantly lower than ovarian carcinoma lacking BRCA1/2 mutations (median = 28). In the JHU cohort, tumors with germline BRCA2 mutations had higher HRD scores (median = 27) than those with germline ATM or CHEK2 mutations (median = 16.5 and 9, respectively). We assessed HRD score (defined as the sum of loss-of-heterozygosity, telomeric allelic imbalance, and large-scale state transitions) in three cohorts of primary prostate cancer, including a Johns Hopkins University (JHU) cohort with germline mutations in BRCA2, ATM, or CHEK2 (n = 64), the TCGA cohort (n = 391), and the PROGENE cohort (n = 102). Given the recent FDA approval of two PARP inhibitors for prostate cancer, HRD score analysis could help to refine treatment selection.

homologous recombination deficiency (HRD) score integrates three DNA-based measures of genomic instability, and has been understudied in prostate cancer. 12 Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

11 Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

10 CeRePP Sorbonne Université, Paris, France.

9 Department of Urology and Predictive Onco-Urology Group, APHP-Sorbonne University, Paris, France.

8 Division of Cancer and Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London, UK.

7 Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

6 Myriad Genetics, Salt Lake City, UT, USA.

5 Department of Urology, Northwestern University, Chicago, IL, USA.

4 Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA. 3 Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 2 Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

1 Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.