Annals of Oncology 22: 1127–1132, 2011
Published online 17 November 2010
Survival in epithelial ovarian cancer: a multivariate
analysis incorporating BRCA mutation status and
D. J. Gallagher1,2, J. A. Konner1, K. M. Bell-McGuinn1, J. Bhatia2, P. Sabbatini1,
C. A. Aghajanian1, K. Offit2, R. R. Barakat3, D. R. Spriggs1& N. D. Kauff2,3*
1Gynecologic Medical Oncology Service, Division of Solid Tumor Oncology, Department of Medicine;2Clinical Genetics Service, Division of Solid Tumor Oncology,
Department of Medicine;3Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA
Received 13 July 2010; revised 17 August 2010; accepted 18 August 2010
Background: Patients with BRCA-associated ovarian cancer (OC) have a survival advantage over those with
sporadic OC. To further explore this, we examined the impact of prognostic factors on disease-free survival (DFS) and
overall survival (OS) in patients with known BRCA mutation status.
Patients and methods: We reviewed stage III–IV OC patients treated at our institution between 1 December 1996
and 30 September 2006 and also tested on protocol for BRCA mutations. Impact on DFS and OS was determined by
Kaplan–Meier analysis and a Cox proportional hazards model.
Results: Of the 110 patients, 36 had deleterious BRCA mutations [BRCA (+)] and 74 were BRCA wild type [BRCA(2)].
Thirty-one of 36 (86%) BRCA (+) and 60 of 74 (81%) BRCA (2) patients were platinum sensitive (P = 0.60). Median OS
was longer for BRCA (+) patients (not reached versus 67.8 months; P = 0.02), but DFS was similar (26.9 versus 24.0,
P = 0.3). On multivariate analysis, OS correlated with primary platinum sensitivity [HR = 0.15; 95% CI (confidence
interval) 0.06–0.34] and BRCA (+) mutation status (HR = 0.33; 95% CI 0.12–0.86).
Conclusions: BRCA mutation status predicted OS independent of primary platinum sensitivity, suggesting that
underlying tumor biology contributes to disease outcome and may be worthy of consideration in future clinical trial
Key words: BRCA, ovarian cancer, platinum sensitivity, survival
Almost 22 000 new cases of epithelial ovarian cancer (OC) are
expected in the United States in 2009 . Between 8% and 13%
of these will be due to a hereditary susceptibility [2–4], with
mutations in BRCA1 or BRCA2 accounting for the majority.
BRCA-associated cancers are typically of serous histology,
moderate to high grade, advanced stage, and diagnosed at
a younger age than sporadic OCs .
Rubin et al.  first reported in 1996 that BRCA-associated
OC had a better prognosis than sporadic OC. Close to a dozen
studies have since investigated this finding but interpretation of
results has been limited by inadequate adjustment for known
prognostic factors, retrospective design, short follow-up, and
nonuniform treatment of cases and controls . A large study
of 779 Israeli women reported, with a median follow-up of 6.2
years, that BRCA-associated OC was associated with improved
survival compared with sporadic disease (median survival, 55.7
versus 37.9 months, P = 0.002) . A previous study reported
a similar survival advantage for BRCA(+) OC and additionally
analyzed survival by BRCA mutation type . In this series of
88 BRCA-associated cancers (67 BRCA1 and 21 BRCA2) and
101 sporadic cancers, median survival in BRCA1(+) patients
was significantly longer than sporadic cases (P = 0.008), and
there was a nonsignificant trend toward better survival for
BRCA2-associated cases (P = 0.09). The authors postulated that
this better prognosis was due to either a different biology or
a better response to treatment.
Preclinical data suggest that BRCA-associated OC is
particularly sensitive to platinum-based chemotherapy [9, 10],
and clinical data appear to support this hypothesis. Tan et al.
 reported significantly greater response to first-, second-,
and third-line platinum-based chemotherapy for BRCA-
associated OC compared with sporadic disease, and upon
relapse, BRCA-associated OC appears to progress more slowly.
To examine if the improved outcome of BRCA-associated OC
is due to enhanced chemosensitivity or to other biologic
differences, we investigated whether known prognostic factors,
including platinum sensitivity, explained any observed
differences in survival, between BRCA(+) and BRCA(2)
*Correspondence to: Dr N. D. Kauff, Clinical Genetics and Gynecology Services, Memorial
Sloan-Kettering Cancer Center, 1275 York Avenue, Box 295, New York, NY 10065,
USA. Tel: +1-646-888-4082; Fax: +1-646-888-4075; E-mail: firstname.lastname@example.org
ª The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: email@example.com
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Annals of Oncology
1132 | Gallagher et al. Volume 22|No. 5|May 2011
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