Modification of homologous recombination deficiency score threshold and association with long‐term survival in epithelial ovarian cancer

Jeffrey A. How, Amir A. Jazaeri, Bryan Fellman, Molly S. Daniels, Suzanna Penn, Cara Solimeno, Ying Yuan, Kathleen Schmeler, Jerry S. Lanchbury, Kirsten Timms, Karen H. Lu, Melinda S. Yates

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

New therapies, such as poly‐ADP ribose polymerase inhibitors (PARPi), and immuno-therapy treatments have generated great interest in enhancing individualized molecular profiling of epithelial ovarian cancer (EOC) to improve management of the disease. In EOC patients, putative biomarkers for homologous recombination deficiency (HRD), microsatellite instability (MSI), and tumor mutational burden (TMB) were characterized and correlated with survival outcomes. A se-ries of 300 consecutive EOC patients were enrolled. Patients underwent neoadjuvant chemotherapy (n = 172) or primary cytoreductive surgery (n = 128). Molecular profiling and survival analyses were restricted to the primary cytoreductive surgery cohort due to tissue availability. All patients underwent germline testing for HRD‐ and MSI‐related gene mutations. When sufficient tissue was avail-able, screening for somatic BRCA1/2 mutations, BRCA1 promoter methylation, HRD score (a meas-ure of genomic instability), MSI, and TMB testing were performed. HRD score ≥33 was associated with improved overall survival on multivariable analysis. In the era of biomarker‐driven clinical care, HRD score ≥33 may be a useful adjunctive prognostic tool and should be evaluated in future studies to predict PARPi benefits.

Original languageEnglish (US)
Article number946
Pages (from-to)1-18
Number of pages18
JournalCancers
Volume13
Issue number5
DOIs
StatePublished - Mar 1 2021

Keywords

  • Epithelial ovarian cancer
  • Homologous recombination deficiency
  • Homologous recombination deficiency score
  • Microsatellite instability
  • Survival
  • Tumor mutational burden

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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