Improved survival for BRCA2-associated serous ovarian cancer compared with both BRCA-negative and BRCA1-associated serous ovarian cancer Journal Article


Authors: Hyman, D. M.; Zhou, Q.; Iasonos, A.; Grisham, R. N.; Arnold, A. G.; Phillips, M. F.; Bhatia, J.; Levine, D. A.; Aghajanian, C.; Offit, K.; Barakat, R. R.; Spriggs, D. R.; Kauff, N. D.
Article Title: Improved survival for BRCA2-associated serous ovarian cancer compared with both BRCA-negative and BRCA1-associated serous ovarian cancer
Abstract: BACKGROUND: Multiple observational studies have suggested that breast cancer gene (BRCA)-associated ovarian cancers have improved survival compared with BRCA-negative ovarian cancers. However, most of those studies combined BRCA1 and BRCA2 patients or evaluated only BRCA1 patients. The objective of the current study was to examine whether BRCA1-associated and BRCA2-associated ovarian cancers were associated with different outcomes. METHODS: This was a single-institution, retrospective analysis of patients who had a new diagnosis of histologically confirmed stage III or IV serous ovarian, fallopian tube, or primary peritoneal cancer between January 1, 1996 and February 1, 2011 and who underwent BRCA mutation testing on 1 of 2 institutional review board-approved follow-up studies. Patients who had been tested for BRCA mutations beyond 24 months of diagnosis were excluded from analysis to minimize selection bias from including patients who were referred for genetic testing because of long survival. RESULTS: Data from 190 patients (143 BRCA-negative patients, 30 BRCA1-positive patients, and 17 BRCA2-positive patients) were analyzed. During the study period, 73 deaths were observed (60 BRCA-negative patients, 10 BRCA1-positive patients, 3 BRCA2-positive patients). The median follow-up for the remaining 117 survivors was 2.5 years. At 3 years, 69.4%, 90.7%, and 100% of BRCA-negative patients, BRCA1-positive patients, and BRCA2-positive patients were alive, respectively. On univariate analysis, age, BRCA2 mutations, debulking status, and type of first-line therapy (intravenous or intraperitoneal) were significant predictors of overall survival. On multivariate analysis, BRCA2 mutations (hazard ratio, 0.20; 95% confidence interval, 0.06-0.65; P =.007), but not BRCA1 mutations (hazard ratio, 0.70; 95% confidence interval, 0.36-1.38; P =.31), predicted for improved overall survival compared with BRCA-negative patients. When carriers of BRCA2 mutations were directly compared with carriers of BRCA1 mutations, BRCA2 mutations appeared to confer improved overall survival (hazard ratio, 0.29; 95% confidence interval, 0.08-1.05; P =.060), although this finding did not reach significance. CONCLUSIONS: The current data suggests that BRCA2 mutations confer an overall survival advantage compared with either being BRCA-negative or having a BRCA1 mutation in high-grade serous ovarian cancer. This finding may have important implications for clinical trial design. Copyright © 2011 American Cancer Society.
Keywords: adult; cancer survival; controlled study; aged; middle aged; primary tumor; major clinical study; overall survival; mutation; histopathology; cytotoxic agent; cancer patient; cancer staging; follow up; cancer grading; ovarian cancer; cytoreductive surgery; ovarian neoplasms; ovary cancer; peritoneum cancer; mutational analysis; brca1 protein; brca2 protein; heterozygote; retrospective study; cancer mortality; cancer survivor; genes, brca1; genes, brca2; age distribution; genetic screening; brca1; brca2; patient referral; uterine tube tumor; survival prediction; poly(adp-ribose); polymerase inhibitors; serous ovarian cancer
Journal Title: Cancer
Volume: 118
Issue: 15
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2012-08-01
Start Page: 3703
End Page: 3709
Language: English
DOI: 10.1002/cncr.26655
PROVIDER: scopus
PUBMED: 22139894
PMCID: PMC3625663
DOI/URL:
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 4 September 2012" - "CODEN: CANCA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Kenneth Offit
    507 Offit
  2. Richard R Barakat
    586 Barakat
  3. Noah Kauff
    122 Kauff
  4. Douglas A Levine
    356 Levine
  5. Qin Zhou
    120 Zhou
  6. Alexia Elia Iasonos
    179 Iasonos
  7. Rachel Nicole Grisham
    35 Grisham
  8. David Hyman
    181 Hyman
  9. David R Spriggs
    309 Spriggs
  10. Jasmine Bhatia
    11 Bhatia
  11. Angela Arnold
    24 Arnold