Clinicopathological features of homologous recombination deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum and survival
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 clinicopathological features, chemotherapy response and survival outcomes of EOC patie...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Association of Cancer Research
2012
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/33769/ http://irep.iium.edu.my/33769/ http://irep.iium.edu.my/33769/ http://irep.iium.edu.my/33769/1/33769.pdf |
| Summary: | 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 clinicopathological features,
chemotherapy response and survival outcomes of EOC patients. 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 vs. HR deficient patients. Compared to HR
competent patients, the HRD group was predominantly serous with a higher median
CA125 at presentation. HRD was associated with higher ex vivo PARP inhibitor
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. |
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