Clinicopathological features of homologous recombination-deficient epithelial ovarian cancers: Sensitivity to PARP inhibitors, platinum, and survival

Asima Mukhopadhyay, Elizabeth R Plummer, Ahmed Elattar, San Soohoo, Bisha Uzir, Jennifer Quinn-O'Brien, W Glenn McCluggage, Perry Maxwell, Harriet Aneke, Nicola J Curtin, Richard J Edmondson

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Abstract

Up to 50% of epithelial ovarian cancers (EOC) display defects in the homologous recombination (HR) pathway. We sought to determine the ramifications of the homologous recombination-deficient (HRD) status on the clinicopathologic features, chemotherapy response, and survival outcomes of patients with EOCs. HR status was determined in primary cultures from ascitic fluid in 50 chemotherapy-naïve patients by a functional RAD51 immunofluorescence assay and correlated with in vitro sensitivity to the PARP inhibitor (PARPi), rucaparib. All patients went on to receive platinum-based chemotherapy; platinum sensitivity, tumor progression, and overall survival were compared prospectively in HR-competent versus HRD patients. Compared with HR-competent patients, the HRD group was predominantly serous with a higher median CA125 at presentation. HRD was associated with higher ex vivo PARPi sensitivity and clinical platinum sensitivity. Median follow-up duration was 14 months; patients in the HRD group had lower tumor progression rates at 6 months, lower overall/disease-specific death rates at 12 months, and higher median survival. We therefore suggest that HRD as predicted by a functional RAD51 assay correlates with in vitro PARPi sensitivity, clinical platinum sensitivity, and improved survival outcome.
Original languageEnglish
Pages (from-to)5675-82
Number of pages8
JournalCancer Research
Volume72
Issue number22
DOIs
Publication statusPublished - 2012

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    Mukhopadhyay, A., Plummer, E. R., Elattar, A., Soohoo, S., Uzir, B., Quinn-O'Brien, J., McCluggage, W. G., Maxwell, P., Aneke, H., Curtin, N. J., & Edmondson, R. J. (2012). Clinicopathological features of homologous recombination-deficient epithelial ovarian cancers: Sensitivity to PARP inhibitors, platinum, and survival. Cancer Research, 72(22), 5675-82. https://doi.org/10.1158/0008-5472.CAN-12-0324