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

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...

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Main Authors: Mukhophadyay, Asima, Plummer, Elizabeth R, Elattar, Ahmed, San, SooHoo, Uzir, Bisha Fathamah, Quinn, Jennifer E, Edmondson, Richard J, Curtin, Nicola J, Harriet, Aneke, Maxwell, Perry, McCluggage, W Glenn
Format: Article
Language:English
Published: American Association of Cancer Research 2012
Subjects:
RB Pathology
RG Gynecology and obstetrics
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
id iium-33769
recordtype eprints
spelling iium-337692015-09-04T08:18:49Z http://irep.iium.edu.my/33769/ Clinicopathological features of homologous recombination deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum and survival Mukhophadyay, Asima Plummer, Elizabeth R Elattar, Ahmed San, SooHoo Uzir, Bisha Fathamah Quinn, Jennifer E Edmondson, Richard J Curtin, Nicola J Harriet, Aneke Maxwell, Perry McCluggage, W Glenn RB Pathology RG Gynecology and obstetrics 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. American Association of Cancer Research 2012-10-11 Article PeerReviewed application/pdf en http://irep.iium.edu.my/33769/1/33769.pdf Mukhophadyay, Asima and Plummer, Elizabeth R and Elattar, Ahmed and San, SooHoo and Uzir, Bisha Fathamah and Quinn, Jennifer E and Edmondson, Richard J and Curtin, Nicola J and Harriet, Aneke and Maxwell, Perry and McCluggage, W Glenn (2012) Clinicopathological features of homologous recombination deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum and survival. Cancer Research, 72 (22). pp. 5675-5682. ISSN 1538-7445 (O), 0008-5472 (P) (Unpublished) http://cancerres.aacrjournals.org/content/early/2012/10/11/0008-5472.CAN-12-0324.abstract 10.1158/0008-5472.CAN-12-0324
repository_type Digital Repository
institution_category Local University
institution International Islamic University Malaysia
building IIUM Repository
collection Online Access
language English
topic RB Pathology
RG Gynecology and obstetrics
spellingShingle RB Pathology
RG Gynecology and obstetrics
Mukhophadyay, Asima
Plummer, Elizabeth R
Elattar, Ahmed
San, SooHoo
Uzir, Bisha Fathamah
Quinn, Jennifer E
Edmondson, Richard J
Curtin, Nicola J
Harriet, Aneke
Maxwell, Perry
McCluggage, W Glenn
Clinicopathological features of homologous recombination deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum and survival
description 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.
format Article
author Mukhophadyay, Asima
Plummer, Elizabeth R
Elattar, Ahmed
San, SooHoo
Uzir, Bisha Fathamah
Quinn, Jennifer E
Edmondson, Richard J
Curtin, Nicola J
Harriet, Aneke
Maxwell, Perry
McCluggage, W Glenn
author_facet Mukhophadyay, Asima
Plummer, Elizabeth R
Elattar, Ahmed
San, SooHoo
Uzir, Bisha Fathamah
Quinn, Jennifer E
Edmondson, Richard J
Curtin, Nicola J
Harriet, Aneke
Maxwell, Perry
McCluggage, W Glenn
author_sort Mukhophadyay, Asima
title Clinicopathological features of homologous recombination deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum and survival
title_short Clinicopathological features of homologous recombination deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum and survival
title_full Clinicopathological features of homologous recombination deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum and survival
title_fullStr Clinicopathological features of homologous recombination deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum and survival
title_full_unstemmed Clinicopathological features of homologous recombination deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum and survival
title_sort clinicopathological features of homologous recombination deficient epithelial ovarian cancers: sensitivity to parp inhibitors, platinum and survival
publisher American Association of Cancer Research
publishDate 2012
url 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
first_indexed 2023-09-18T20:48:50Z
last_indexed 2023-09-18T20:48:50Z
_version_ 1777409857646755840

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