Clinical significance of homologous recombination deficiency score testing in endometrial Cancer
| Autor: | Anil K. Sood, Robert L. Coleman, Selanere Mangala, Placede Tshiaba, Keith A. Baggerly, Wei Hu, Thomas P. Conrads, Kirsten Timms, Chris Neff, Ying Wang, Kari L. Ring, Shannon N. Westin, Karen H. Lu, K.M. Darcy, R.L. Dood, G.L. Maxwell, Russell Broaddus, Gabriel Lopez-Berestein, Shannon Gallagher, Jean H. Siedel |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Article Olaparib 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Uterine cancer Internal medicine Humans Medicine Clinical significance Homologous Recombination Receiver operating characteristic business.industry Endometrial cancer Obstetrics and Gynecology Microsatellite instability Middle Aged medicine.disease Endometrial Neoplasms 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cohort Female business Homologous Recombination Deficiency |
| Zdroj: | Gynecol Oncol |
| ISSN: | 0090-8258 |
| DOI: | 10.1016/j.ygyno.2020.12.010 |
| Popis: | BACKGROUND: Homologous recombination deficiency (HRD) score is related to chemotherapy response in some cancers, but its role in endometrial cancer in not known. We determined frequency and clinical significance of alterations in the HR pathway in endometrial cancer. METHODS: 253 endometrioid endometrial adenocarcinoma (EEA) samples from two independent cohorts (discovery and replication) were tested for HRD score using the Myriad HRD assay, microsatellite instability (MSI) and tumor mutation burden (TMB) using a next generation sequencing assay. HRD scores were also generated on endometrial cancer cell lines and in vivo response to olaparib was assessed. RESULTS: ROC curves were employed to determine optimal cutoffs of HRD in relation to survival impact in endometrial cancer and a cutoff of HRD ≥ 4 was suggested for DFS using discovery cohort. Patients from two independent cohorts with HRD score ≥ 4 trended toward worse survival as compared to those with HRD score |
| Databáze: | OpenAIRE |
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