Imperial College London
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ProfessorBobBrown

Faculty of Medicine, Department of Surgery & Cancer

Senior Research Investigator
 
 
 
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Contact

 

+44 (0)20 7594 1804b.brown Website

 
 
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Assistant

 

Ms Sophie Lions +44 (0)20 7594 2792

 
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Location

 

1 007Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Stronach:2018:10.1158/1541-7786.MCR-18-0034,
author = {Stronach, EA and Paul, J and Timms, KM and Hughes, E and Brown, K and Neff, C and Perry, M and Gutin, A and El-Bahrawy, M and Steel, JH and Liu, X and Lewsley, L-A and Siddiqui, N and Gabra, H and Lanchbury, JS and Brown, R},
doi = {10.1158/1541-7786.MCR-18-0034},
journal = {Molecular Cancer Research},
pages = {1103--1111},
title = {Biomarker assessment of HR deficiency, tumor BRCA1/2 mutations and CCNE1 copy number in ovarian cancer: associations with clinical outcome following platinum monotherapy},
url = {http://dx.doi.org/10.1158/1541-7786.MCR-18-0034},
volume = {16},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The current study evaluated three biomarkers [homologous recombination deficiency (HRD), tumor BRCA1/2 (tBRCA) mutations, and CCNE1 copy number variation (CNV)] in ovarian tumors from patients enrolled on the SCOTROC4 clinical trial for associations with outcome following carboplatinum monotherapy. Ovarian tumors (n=250), with high-grade serous (HGSOC) subgroup analysis (n=179), were classified as HRD positive (HRD score ≥42 or tBRCA mutation) and as CCNE1 amplification positive (CCNE1 CNV score >2.4). Seventy-four (30%) tumors were HRD positive, including 34 (14%) with tBRCA mutations. Forty-seven (19%) were CCNE1 amplification positive, all of which were tBRCA wild-type. HRD and tBRCA, but not CCNE1 amplification, were significantly associated with CA125 complete response in the entire cohort (HRD, p=0.00015; tBRCA p=0.0096), and the HGSOC subgroup (HRD, p= 0.0016; tBRCA p=0.032). HRD and lack of CCNE1 amplification were associated with improved progression free survival (PFS) and overall survival (OS) in the full cohort and HGSOC subgroup (HRD, p=0.00021; CCNE1 status p=0.038). HRD remained significant for OS and PFS after adjusting for clinical factors, while CCNE1 status only remained significant for PFS. Patients with HRD positive tumors had greater PFS and OS benefit from platinum dose intensification than HRD negative tumors (p=0.049 and p=0.035, respectively). An alternative exploratory HRD score threshold (≥33 or tBRCA mutation) was also significantly associated with both PFS and OS in the HGSOC subset. IMPLICATIONS: HRD, tumor BRCA1/2 mutations and absence of CCNE1 amplification are associated with improved survival of ovarian cancer patients treated with platinum monotherapy and HRD positive patients may benefit from platinum dose intensification.
AU  - Stronach,EA
AU  - Paul,J
AU  - Timms,KM
AU  - Hughes,E
AU  - Brown,K
AU  - Neff,C
AU  - Perry,M
AU  - Gutin,A
AU  - El-Bahrawy,M
AU  - Steel,JH
AU  - Liu,X
AU  - Lewsley,L-A
AU  - Siddiqui,N
AU  - Gabra,H
AU  - Lanchbury,JS
AU  - Brown,R
DO  - 10.1158/1541-7786.MCR-18-0034
EP  - 1111
PY  - 2018///
SN  - 1541-7786
SP  - 1103
TI  - Biomarker assessment of HR deficiency, tumor BRCA1/2 mutations and CCNE1 copy number in ovarian cancer: associations with clinical outcome following platinum monotherapy
T2  - Molecular Cancer Research
UR  - http://dx.doi.org/10.1158/1541-7786.MCR-18-0034
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29724815
UR  - http://mcr.aacrjournals.org/content/16/7/1103
UR  - http://hdl.handle.net/10044/1/59251
VL  - 16
ER  -
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