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Open AccessArticle

Modification of Homologous Recombination Deficiency Score Threshold and Association with Long-Term Survival in Epithelial Ovarian Cancer

1
Department of Gynecologic Oncology and Reproductive Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2
Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
3
Department of Clinical Cancer Genetics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
4
Myriad Genetics, Salt Lake City, UT 84108, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Kimberly K. Leslie, David G. Mutch, Doris M. Benbrook and Kristina W. Thiel
Cancers 2021, 13(5), 946; https://doi.org/10.3390/cancers13050946
Received: 1 February 2021 / Revised: 19 February 2021 / Accepted: 19 February 2021 / Published: 24 February 2021
Knowledge of ovarian cancer molecular characteristics is increasingly crucial to individualizing and optimizing treatment strategies for this heterogeneous disease. Molecular features such as germline or somatic mutations, homologous recombination deficiency (HRD) status, microsatellite instability, and tumor mutational burden are associated with increased susceptibility to poly-ADP ribose polymerase inhibitors (PARPi) or immunotherapy. Our aim was to characterize these molecular features among ovarian cancer patients and determine their association with survival. Two different HRD score thresholds were evaluated: one currently used in clinics (≥42) and another proposed as a new threshold (≥33). An HRD score ≥33 was associated with improved overall survival in ovarian cancer. As HRD assays are increasingly used for treatment planning, future studies should evaluate an HRD score threshold of ≥33 compared to the currently used threshold of ≥42 for PARPi use.
New therapies, such as poly-ADP ribose polymerase inhibitors (PARPi), and immunotherapy 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 series 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 available, screening for somatic BRCA1/2 mutations, BRCA1 promoter methylation, HRD score (a measure 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. View Full-Text
Keywords: epithelial ovarian cancer; homologous recombination deficiency; homologous recombination deficiency score; microsatellite instability; tumor mutational burden; survival epithelial ovarian cancer; homologous recombination deficiency; homologous recombination deficiency score; microsatellite instability; tumor mutational burden; survival
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MDPI and ACS Style

How, J.A.; Jazaeri, A.A.; Fellman, B.; Daniels, M.S.; Penn, S.; Solimeno, C.; Yuan, Y.; Schmeler, K.; Lanchbury, J.S.; Timms, K.; Lu, K.H.; Yates, M.S. Modification of Homologous Recombination Deficiency Score Threshold and Association with Long-Term Survival in Epithelial Ovarian Cancer. Cancers 2021, 13, 946. https://doi.org/10.3390/cancers13050946

AMA Style

How JA, Jazaeri AA, Fellman B, Daniels MS, Penn S, Solimeno C, Yuan Y, Schmeler K, Lanchbury JS, Timms K, Lu KH, Yates MS. Modification of Homologous Recombination Deficiency Score Threshold and Association with Long-Term Survival in Epithelial Ovarian Cancer. Cancers. 2021; 13(5):946. https://doi.org/10.3390/cancers13050946

Chicago/Turabian Style

How, Jeffrey A.; Jazaeri, Amir A.; Fellman, Bryan; Daniels, Molly S.; Penn, Suzanna; Solimeno, Cara; Yuan, Ying; Schmeler, Kathleen; Lanchbury, Jerry S.; Timms, Kirsten; Lu, Karen H.; Yates, Melinda S. 2021. "Modification of Homologous Recombination Deficiency Score Threshold and Association with Long-Term Survival in Epithelial Ovarian Cancer" Cancers 13, no. 5: 946. https://doi.org/10.3390/cancers13050946

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