Journal Mobile Options
Table of Contents
Vol. 85, No. 2, 2013
Issue release date: August 2013
Oncology 2013;85:122-127

The Different Impact of BRCA Mutations on the Survival of Epithelial Ovarian Cancer Patients: A Retrospective Single-Center Experience

Lorusso D. · Cirillo F. · Mancini M. · Spatti G.B. · Grijuela B. · Ditto A. · Raspagliesi F.
Gynecologic Oncology Unit, Fondazione ‘IRCCS' National Cancer Institute, Milan, Italy

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Objectives: The objective of this study was to examine whether the oncologic outcomes of BRCA1-associated and BRCA2-associated ovarian cancers correlate differently. Methods: Genetic data and clinical characteristics were correlated with progression-free survival (PFS) and overall survival (OS). Results: Data from 147 BRCA-mutated patients (119 BRCA1-positive and 28 BRCA2-positive) were analyzed. At a median follow-up of 69 months, the median PFS was 27.2 and 45.46 months for BRCA1 and BRCA2 patients, respectively (p = 0.03). Median OS was 77.23 and 111.47 months for BRCA1 and BRCA2 patients, respectively (p = 0.08). Conclusion:BRCA2 mutations confer PFS and a trend to OS advantage compared with the BRCA1 mutation in BRCA-mutated epithelial ovarian cancer patients.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer Statistics, 2009. CA Cancer J Clin 2009;59:225-249.
  2. Lynch HT, Snyder CL, Lynch JF, Riley BD, Rubinstein WS: Hereditary breast-ovarian cancer at the bedside: role of the medical oncologist. J Clin Oncol 2003;21:740-753.
  3. Sinilnikova OM, Mazoyer S, Bonnardel C, Lynch HT, Narod SA, Lenoir GM: BRCA1 and BRCA2 mutations in breast and ovarian cancer syndrome: reflection on the Creighton University historical series of high-risk families. Fam Cancer 2006;5:15-20.
  4. Simon MS, Petrucelli N: Hereditary breast and ovarian cancer syndrome: the impact of race on uptake of genetic counseling and testing. Methods Mol Biol 2009;471:487-500.
  5. Quinn JE, Carser JE, James CR, Kennedy RD, Harkin DP: BRCA1 and implications for response to chemotherapy in ovarian cancer. Gynecol Oncol 2009;113:134-142.
  6. O'Donovan PJ, Livingston DM: BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair. Carcinogenesis 2010;31:961-967.
  7. Tutt A, Ashworth A: The relationship between the roles of BRCA genes in DNA repair and cancer predisposition. Trends Mol Med 2002;8:571-576.
  8. Venkitaraman AR: Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 2002;108:171-182.
  9. Tan DS, Rothermundt C, Thomas K, et al: ‘BRCAness' syndrome in ovarian cancer: a case-control study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations. J Clin Oncol 2008;26:5530-5536.
  10. Cass I, Baldwin RL, Varkey T, Moslehi R, Narod SA, Karlan BY: Improved survival in women with BRCA-associated ovarian carcinoma. Cancer 2003;97:2187-2195.
  11. Foulkes WD: BRCA1 and BRCA2: chemosensitivity, treatment outcomes and prognosis. Fam Cancer 2006;5:135-142.
  12. Chetrit A, Hirsh-Yechezkel G, Ben-David Y, Lubin F, Friedman E, Sadetzki S: Effect of BRCA1/2 mutations on long-term survival of patients with invasive ovarian cancer: the National Israeli Study of Ovarian Cancer. J Clin Oncol 2008;26:20-25.
  13. Boyd J, Sonoda Y, Federici MG, et al: Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 2000;283:2260-2265.
  14. Buller RE, Shahin MS, Geisler JP, Zogg M, De Young BR, Davis CS: Failure of BRCA1 dysfunction to alter ovarian cancer survival. Clin Cancer Res 2002;8:1196-1202.

    External Resources

  15. Pharoah PD, Easton DF, Stockton DL, Gayther S, Ponder BA, United Kingdom Coordinating Committee for Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group: Survival in familial, BRCA1-associated, and BRCA2-associated epithelial ovarian cancer. Cancer Res 1999;59:868-871.

    External Resources

  16. Antoniou A, Pharoah PD, Narod S, et al: Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 2003;72:1117-1130.
  17. Risch HA, McLaughlin JR, Cole DE, et al: Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 2001;68:700-710.
  18. Foulkes WD, Metcalfe K, Sun P, et al: Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological type. Clin Cancer Res 2004;10:2029-2034.
  19. Yang D, Khan S, Sun Y, et al: Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 2011;306:1557-1565.
  20. Bolton KL, Chenevix-Trench G, Goh C, et al: Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. Cancer Genome Atlas Research Network. JAMA 2012;307:382-390.
  21. Szabo C, Masiello A, Ryan JF, Brody LC: The breast cancer information core: database design, structure, and scope. Hum Mutat 2000;16:123-131.
  22. Antoniou AC, Sinilnikova OM, Simard J, et al: RAD51 135G->C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies. Am J Hum Genet 2007;81:1186-1200.
  23. Buisson M, Anczuków O, Zetoune AB, Ware MD, Mazoyer S: The 185delAG mutation (c.68_69delAG) in the BRCA1 gene triggers translation reinitiation at a downstream AUG codon. Hum Mutat 2006;27:1024-1029.
  24. Perrin-Vidoz L, Sinilnikova OM, Stoppa-Lyonnet D, Lenoir GM, Mazoyer S: The nonsense-mediated mRNA decay pathway triggers degradation of most BRCA1 mRNAs bearing premature termination codons. Hum Mol Genet 2002;11:2805-2814.
  25. The Breast Cancer Linkage Consortium: Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999;91:1310-1316.
  26. Thompson D, Easton DF, Breast Cancer Linkage Consortium: Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 2002;94:1358-1365.
  27. Davies AA, Masson JY, McIlwraith MJ, et al: Role of BRCA2 in control of the RAD51 recombination and DNA repair protein. Mol Cell 2001;7:273-282.
  28. Kim H, Chen J, Yu X: Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science 2007;316:1202-1205.
  29. Kim H, Huang J, Chen J: CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage response. Nat Struct Mol Biol 2007;14:710-715.
  30. Liu Z, Wu J, Yu X: CCDC98 targets BRCA1 to DNA damage sites. Nat Struct Mol Biol 2007;14:716-720.
  31. Wang B, Matsuoka S, Ballif BA, et al: Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science 2007;316:1194-1198.
  32. Yarden RI, Pardo-Reoyo S, Sgagias M, Cowan KH, Brody LC: BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage. Nat Genet 2002;30:285-289.
  33. Joukov V, Groen AC, Prokhorova T, et al: The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly. Cell 2006;127:539-552.
  34. Lou Z, Minter-Dykhouse K, Chen J: BRCA1 participates in DNA decatenation. Nat Struct Mol Biol 2005;12:589-593.
  35. Sankaran S, Crone DE, Palazzo RE, Parvin JD: BRCA1 regulates gamma-tubulin binding to centrosomes. Cancer Biol Ther 2007;6:1853-1857.
  36. Starita LM, Machida Y, Sankaran S, et al: BRCA1-dependent ubiquitination of gamma-tubulin regulates centrosome number. Mol Cell Biol 2004;24:8457-8466.
  37. Quinn JE, James CR, Stewart GE, et al: BRCA1 mRNA expression levels predict for overall survival in ovarian cancer after chemotherapy. Clin Cancer Res 2007;13:7413-7420.
  38. Quinn JE, Kennedy RD, Mullan PB, et al: BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res 2003;63:6221-6228.

    External Resources

  39. Byrski T, Gronwald J, Huzarski T, et al: Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers. Breast Cancer Res Treat 2008;108:289-296.
  40. Yang D, Khan S, Sun Y, et al: Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 2011;306:1557-1565 (erratum published in JAMA 2012;307:363).
  41. Hyman DM, Zhou Q, Iasonos A, et al: Improved survival for BRCA2-associated serous ovarian cancer compared with both BRCA-negative and BRCA1-associated serous ovarian cancer. Cancer 2012;118:3703-8709.
  42. Liu J, Cristea MC, Frankel P, et al: Clinical characteristics and outcomes of BRCA-associated ovarian cancer: genotype and survival. Cancer Genet 2012;205:34-41.
  43. Dann RB, DeLoia JA, Timms KM, et al: BRCA1/2 mutations and expression: response to platinum chemotherapy in patients with advanced stage epithelial ovarian cancer. Gynecol Oncol 2012;125:677-682.
  44. Cancer Genome Atlas Research Network: Integrated genomic analyses of ovarian carcinoma. Nature 2011;474:609-615.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50