Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 787143, 11 pages
http://dx.doi.org/10.1155/2014/787143
Review Article

BRCA-Associated Ovarian Cancer: From Molecular Genetics to Risk Management

1Dipartimento di Scienze Mediche e Chirurgiche, Unità di Genetica Medica, Università di Bologna, Policlinico S. Orsola-Malpighi, Via Massarenti 9 [Pad. 11, 2° Piano], 40138 Bologna, Italy
2SSD Oncologia Ginecologica, AOU di Bologna, Policlinico S. Orsola-Malpighi, 40138 Bologna, Italy
3UO Anatomia Patologica, AOU di Bologna, Policlinico S. Orsola-Malpighi, 40138 Bologna, Italy
4SSD Oncologia Medica, AOU di Bologna, Policlinico S. Orsola-Malpighi, 40138 Bologna, Italy
5Dipartimento Di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, 73100 Lecce, Italy
6UO Genetica Medica, AOU di Bologna, Policlinico S. Orsola-Malpighi, 40138 Bologna, Italy

Received 21 January 2014; Revised 8 July 2014; Accepted 10 July 2014; Published 22 July 2014

Academic Editor: YongSang Song

Copyright © 2014 Giulia Girolimetti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Staples and A. Goodman, “PARP inhibitors in ovarian cancer,” in Ovarian Cancer—A Clinical and Translational Update, I. Díaz-Padilla, Ed., chapter 14, InTech, 2013. View at Google Scholar
  2. K. Yoshida and Y. Miki, “Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage,” Cancer Science, vol. 95, no. 11, pp. 866–871, 2004. View at Publisher · View at Google Scholar · View at Scopus
  3. A. Ashworth, “A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair,” Journal of Clinical Oncology, vol. 26, no. 22, pp. 3785–3790, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. S. Banerjee and S. Kaye, “PARP inhibitors in BRCA gene-mutated ovarian cancer and beyond,” Current Oncology Reports, vol. 13, no. 6, pp. 442–449, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. R. Scully and D. M. Livingston, “In search of the tumour-suppressor functions of BRCA1 and BRCA2,” Nature, vol. 408, no. 6811, pp. 429–432, 2000. View at Publisher · View at Google Scholar · View at Scopus
  6. S. Banerjee, S. B. Kaye, and A. Ashworth, “Making the best of PARP inhibitors in ovarian cancer,” Nature Reviews Clinical Oncology, vol. 7, no. 9, pp. 508–519, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. C. Deng and F. Scott, “Role of the tumor suppressor gene Brca1 in genetic stability and mammary gland tumor formation,” Oncogene, vol. 19, no. 8, pp. 1059–1064, 2000. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Kraakman-van der Zwet, W. J. I. Overkamp, R. E. E. van Lange et al., “Brca2 (XRCC11) deficiency results in radioresistant DNA synthesis and a higher frequency of spontaneous deletions,” Molecular and Cellular Biology, vol. 22, no. 2, pp. 669–679, 2002. View at Publisher · View at Google Scholar · View at Scopus
  9. K. J. Patel, V. P. Yu, H. Lee et al., “Involvement of Brca2 in DNA repair,” Molecular Cell, vol. 1, no. 3, pp. 347–357, 1998. View at Publisher · View at Google Scholar · View at Scopus
  10. A. Tutt, D. Bertwistle, J. Valentine et al., “Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences,” EMBO Journal, vol. 20, no. 17, pp. 4704–4716, 2001. View at Publisher · View at Google Scholar · View at Scopus
  11. Y. B. David, A. Chetrit, G. Hirsh-Yechezkel et al., “Effect of BRCA mutations on the length of survival in epithelial ovarian tumors,” Journal of Clinical Oncology, vol. 20, no. 2, pp. 463–466, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. D. S. P. Tan, C. Rothermundt, K. Thomas 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,” Journal of Clinical Oncology, vol. 26, no. 34, pp. 5530–5536, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. A. C. Magwood, M. M. Mundia, and M. D. Baker, “High levels of wild-type BRCA2 suppress homologous recombination,” Journal of Molecular Biology, vol. 421, no. 1, pp. 38–53, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. P. L. Welcsh, K. N. Owens, and M. C. King, “Insights into the functions of BRCA1 and BRCA2,” Trends in Genetics, vol. 16, no. 2, pp. 69–74, 2000. View at Publisher · View at Google Scholar · View at Scopus
  15. D. S. Shin, L. Pellegrini, D. S. Daniels et al., “Full-length archaeal Rad51 structure and mutants: mechanisms for RAD51 assembly and control by BRCA2,” EMBO Journal, vol. 22, no. 17, pp. 4566–4576, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. K. Somasundaram, “Breast cancer gene 1 (BRCA1): role in cell cycle regulation and DNA repair—perhaps through transcription,” Journal of Cellular Biochemistry, vol. 88, no. 6, pp. 1084–1091, 2003. View at Publisher · View at Google Scholar · View at Scopus
  17. T. T. Paull, E. P. Rogakou, V. Yamazaki, C. U. Kirchgessner, M. Gellert, and W. M. Bonner, “A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage,” Current Biology, vol. 10, no. 15, pp. 886–895, 2000. View at Publisher · View at Google Scholar · View at Scopus
  18. K. Yamane, E. Katayama, and T. Tsuruo, “The BRCT regions of tumor suppressor BRCA1 and of XRCC1 show DNA end binding activity with a multimerizing feature,” Biochemical and Biophysical Research Communications, vol. 279, no. 2, pp. 678–684, 2000. View at Publisher · View at Google Scholar · View at Scopus
  19. A. N. A. Monteiro, “BRCA1: exploring the links to transcription,” Trends in Biochemical Sciences, vol. 25, no. 10, pp. 469–474, 2000. View at Publisher · View at Google Scholar · View at Scopus
  20. D. P. Harkin, J. M. Bean, D. Miklos et al., “Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1,” Cell, vol. 97, no. 5, pp. 575–586, 1999. View at Publisher · View at Google Scholar · View at Scopus
  21. W. D. Foulkes and A. Y. Shuen, “In brief: BRCA1 and BRCA2,” The Journal of Pathology, vol. 230, no. 4, pp. 347–349, 2013. View at Publisher · View at Google Scholar · View at Scopus
  22. P. L. Welcsh and M. C. King, “BRCA1 and BRCA2 and the genetics of breast and ovarian cancer,” Human Molecular Genetics, vol. 10, no. 7, pp. 705–713, 2001. View at Publisher · View at Google Scholar · View at Scopus
  23. T. M. Smith, M. K. Lee, C. I. Szabo et al., “Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1,” Genome Research, vol. 6, no. 11, pp. 1029–1049, 1996. View at Publisher · View at Google Scholar · View at Scopus
  24. J. R. Korenberg and M. C. Rykowski, “Human genome organization: Alu, lines, and the molecular structure of metaphase chromosome bands,” Cell, vol. 53, no. 3, pp. 391–400, 1988. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Nordling, P. Karlsson, J. Wahlström, Y. Engwall, A. Wallgren, and T. Martinsson, “A large deletion disrupts the exon 3 transcription activation domain of the BRCA2 gene in a breast/ovarian cancer family,” Cancer Research, vol. 58, no. 7, pp. 1372–1375, 1998. View at Google Scholar · View at Scopus
  26. M. A. Unger, K. L. Nathanson, K. Calzone et al., “Screening for genomic rearrangements in families with breast and ovarian cancer identifies BRCA1 mutations previously missed by conformation-sensitive gel electrophoresis or sequencing,” American Journal of Human Genetics, vol. 67, no. 4, pp. 841–850, 2000. View at Publisher · View at Google Scholar · View at Scopus
  27. M. Esteller, J. M. Silva, G. Dominguez et al., “Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors,” Journal of the National Cancer Institute, vol. 92, no. 7, pp. 564–569, 2000. View at Publisher · View at Google Scholar · View at Scopus
  28. F. Cai, I. Ge, M. Wang, E. Biskup, X. Lin, and X. Zhong, “Pyrosequencing analysis of BRCA1 methylation level in breast cancer cells,” Tumor Biology, vol. 35, no. 4, pp. 3839–3844, 2013. View at Publisher · View at Google Scholar
  29. Z. X. Yeo, M. Chan, Y. S. Yap, P. Ang, S. Rozen, and A. S. G. Lee, “Improving indel detection specificity of the Ion Torrent PGM benchtop sequencer,” PLoS ONE, vol. 7, no. 9, Article ID e45798, 2012. View at Publisher · View at Google Scholar · View at Scopus
  30. A. M. Augustyn, N. M. Agostino, T. L. Namey, S. Nair, and M. A. Martino, “Two patients with germline mutations in both BRCA1 and BRCA2 discovered unintentionally: a case series and discussion of BRCA testing modalities,” Breast Cancer Research and Treatment, vol. 129, no. 2, pp. 629–634, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Ready, A. M. Gutierrez-Barrera, C. Amos et al., “Cancer risk management decisions of women with BRCA1 or BRCA2 variants of uncertain significance,” The Breast Journal, vol. 17, no. 2, pp. 210–212, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. D. E. Goldgar, D. F. Easton, G. B. Byrnes, A. B. Spurdle, E. S. Iversen, and M. S. Greenblatt, “Genetic evidence and integration of various data sources for classifying uncertain variants into a single model,” Human Mutation, vol. 29, no. 11, pp. 1265–1272, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. A. B. Spurdle, “Clinical relevance of rare germline sequence variants in cancer genes: evolution and application of classification models,” Current Opinion in Genetics and Development, vol. 20, no. 3, pp. 315–323, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. M. P. Vallée, T. C. Francy, M. K. Judkins et al., “Classification of missense substitutions in the BRCA genes: a database dedicated to Ex-UVs,” Human Mutation, vol. 33, no. 1, pp. 22–28, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. E. Beristain, C. Martínez-Bouzas, I. Guerra et al., “Differences in the frequency and distribution of BRCA1 and BRCA2 mutations in breast/ovarian cancer cases from the Basque country with respect to the Spanish population: implications for genetic counselling,” Breast Cancer Research and Treatment, vol. 106, no. 2, pp. 255–262, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. T. S. Frank, A. M. Deffenbaugh, J. E. Reid et al., “Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals,” Journal of Clinical Oncology, vol. 20, no. 6, pp. 1480–1490, 2002. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Konecny, M. Milly, K. Zavodna et al., “Comprehensive genetic characterization of hereditary breast/ovarian cancer families from Slovakia,” Breast Cancer Research and Treatment, vol. 126, no. 1, pp. 119–130, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. F. Marroni, P. Aretini, E. D’Andre et al., “Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations,” European Journal of Human Genetics, vol. 12, no. 11, pp. 899–906, 2004. View at Publisher · View at Google Scholar · View at Scopus
  39. R. Nanda, L. P. Schumm, S. Cummings et al., “Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry,” Journal of the American Medical Association, vol. 294, no. 15, pp. 1925–1933, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. I. J. Seymour, S. Casadei, V. Zampiga et al., “Results of a population-based screening for hereditary breast cancer in a region of North-Central Italy: contribution of BRCA1/2 germ-line mutations,” Breast Cancer Research and Treatment, vol. 112, no. 2, pp. 343–349, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. J. N. Weitzel, V. Lagos, K. R. Blazer et al., “Prevalence of BRCA mutations and founder effect in high-risk Hispanic families,” Cancer Epidemiology, Biomarkers & Prevention, vol. 14, no. 7, pp. 1666–1671, 2005. View at Publisher · View at Google Scholar · View at Scopus
  42. S. A. Gayther, P. Russell, P. Harrington, A. C. Antoniou, D. F. Easton, and B. A. J. Ponder, “The contribution of germline BRCA1 and BRCA2 mutations to familial ovarian cancer: no evidence for other ovarian cancer-susceptibility genes,” American Journal of Human Genetics, vol. 65, no. 4, pp. 1021–1029, 1999. View at Publisher · View at Google Scholar · View at Scopus
  43. H. Anton-Culver, P. P. Cohen, M. E. Gildea, and A. Ziogas, “Characteristics of BRCA1 mutations in a population-based case series of breast and ovarian cancer,” European Journal of Cancer, vol. 36, no. 10, pp. 1200–1208, 2000. View at Publisher · View at Google Scholar · View at Scopus
  44. S. A. Janezic, A. Ziogas, L. M. Krumroy et al., “Germline BRCA1 alterations in a population-based series of ovarian cancer cases,” Human Molecular Genetics, vol. 8, no. 5, pp. 889–897, 1999. View at Publisher · View at Google Scholar · View at Scopus
  45. H. A. Risch, J. R. McLaughlin, D. E. C. Cole et al., “Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada,” Journal of the National Cancer Institute, vol. 98, no. 23, pp. 1694–1706, 2006. View at Publisher · View at Google Scholar · View at Scopus
  46. J. F. Stratton, S. A. Gayther, P. Russell et al., “Contribution of BRCA1 mutations to ovarian cancer,” The New England Journal of Medicine, vol. 336, no. 16, pp. 1125–1130, 1997. View at Google Scholar
  47. K. Alsop, S. Fereday, C. Meldrum et al., “BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian ovarian cancer study group,” Journal of Clinical Oncology, vol. 30, no. 21, pp. 2654–2663, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. S. Zhang, R. Royer, S. Li et al., “Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer,” Gynecologic Oncology, vol. 121, no. 2, pp. 353–357, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. A. V. Stavropoulou, F. Fostira, M. Pertesi et al., “Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer cases,” PLoS ONE, vol. 8, no. 3, Article ID e58182, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. K. de Leeneer, I. Coene, B. Crombez et al., “Prevalence of BRCA1/2 mutations in sporadic breast/ovarian cancer patients and identification of a novel de novo BRCA1 mutation in a patient diagnosed with late onset breast and ovarian cancer: implications for genetic testing,” Breast Cancer Research and Treatment, vol. 132, no. 1, pp. 87–95, 2012. View at Publisher · View at Google Scholar
  51. I. Brozek, K. Ochman, J. Debniak et al., “High frequency of BRCA1/2 germline mutations in consecutive ovarian cancer patients in Poland,” Gynecologic Oncology, vol. 108, no. 2, pp. 433–437, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. T. Y. Smirnova, N. I. Pospekhova, L. N. Lyubchenko et al., “High incidence of mutations in BRCA1 and BRCA2 genes in ovarian cancer,” Bulletin of Experimental Biology and Medicine, vol. 144, no. 1, pp. 83–85, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. M. C. Lim, S. Kang, S. Seo et al., “BRCA1 and BRCA2 germline mutations in Korean ovarian cancer patients,” Journal of Cancer Research and Clinical Oncology, vol. 135, no. 11, pp. 1593–1599, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Boyd, Y. Sonoda, M. G. Federici et al., “Clinicopatholic features of BRCA-linked and sporadic ovarian cancer,” The Journal of the American Medical Association, vol. 283, no. 17, pp. 2260–2265, 2000. View at Publisher · View at Google Scholar · View at Scopus
  55. A. Berchuck, K. Heron, M. E. Carney et al., “Frequency of germline and somatic BRCA1 mutations in ovarian cancer,” Clinical Cancer Research, vol. 4, no. 10, pp. 2433–2437, 1998. View at Google Scholar · View at Scopus
  56. S. R. Lakhani, S. Manek, F. Penault-Llorca et al., “Pathology of ovarian cancers in BRCA1 and BRCA2 carriers,” Clinical Cancer Research, vol. 10, no. 7, pp. 2473–2481, 2004. View at Publisher · View at Google Scholar · View at Scopus
  57. S. C. Rubin, I. Benjamin, K. Behbakht et al., “Clinical and pathological features of ovarian cancer in women with germ- line mutations of BRCA1,” The New England Journal of Medicine, vol. 335, no. 19, pp. 1413–1416, 1996. View at Publisher · View at Google Scholar · View at Scopus
  58. P. A. Shaw, J. R. McLaughlin, R. P. Zweemer et al., “Histopathologic features of genetically determined ovarian cancer,” International Journal of Gynecological Pathology, vol. 21, no. 4, pp. 407–411, 2002. View at Publisher · View at Google Scholar · View at Scopus
  59. B. A. Werness, S. J. Ramus, A. S. Whittemore et al., “Histopathology of familial ovarian tumors in women from families with and without germline BRCA1 mutations,” Human Pathology, vol. 31, no. 11, pp. 1420–1424, 2000. View at Publisher · View at Google Scholar · View at Scopus
  60. N. Mavaddat, D. Barrowdale, I. L. Andrulis et al., “Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: Results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA),” Cancer Epidemiology Biomarkers and Prevention, vol. 21, no. 1, pp. 134–147, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. R. Vang, I. M. Shih, and R. J. Kurman, “Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems,” Advances in Anatomic Pathology, vol. 16, no. 5, pp. 267–282, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. A. Osorio, M. De La Hoya, R. Rodríguez-López et al., “Loss of heterozygosity analysis at the BRCA loci in tumor samples from patients with familial breast cancer,” International Journal of Cancer, vol. 99, no. 2, pp. 305–309, 2002. View at Publisher · View at Google Scholar · View at Scopus
  63. I. J. Jacobs, M. F. Kohler, R. W. Wiseman et al., “Clonal origin of epithelial ovarian carcinoma: analysis by loss of heterozygosity, p53 mutation, and X-chromosome inactivation,” Journal of the National Cancer Institute, vol. 84, no. 23, pp. 1793–1798, 1992. View at Google Scholar · View at Scopus
  64. A. Saleemuddin, A. K. Folkins, L. Garrett et al., “Risk factors for a serous cancer precursor (“p53 signature”) in women with inherited BRCA mutations,” Gynecologic Oncology, vol. 111, no. 2, pp. 226–232, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. N. Turner, A. Tutt, and A. Ashworth, “Hallmarks of “BRCAness” in sporadic cancers,” Nature Reviews Cancer, vol. 4, no. 10, pp. 814–819, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. J. L. Hilton, J. P. Geisler, J. A. Rathe, M. A. Hattermann-Zogg, B. Deyoung, and R. E. Buller, “Inactivation of BRCA1 and BRCA2 in ovarian cancer,” Journal of the National Cancer Institute, vol. 94, no. 18, pp. 1396–1406, 2002. View at Publisher · View at Google Scholar · View at Scopus
  67. C. Wang, A. Horiuchi, T. Imai et al., “Expression of BRCA1 protein in benign, borderline, and malignant epithelial ovarian neoplasms and its relationship to methylation and allelic loss of the BRCA1 gene,” The Journal of Pathology, vol. 202, no. 2, pp. 215–223, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. K. A. Foster, P. Harrington, J. Kerr et al., “Somatic and germline mutations of the BRCA2 gene in sporadic ovarian cancer,” Cancer Research, vol. 56, no. 16, pp. 3622–3625, 1996. View at Google Scholar · View at Scopus
  69. Cancer Genome Atlas Research Network, “Integrated genomic analyses of ovarian carcinoma,” Nature, vol. 474, no. 7353, pp. 609–615, 2011. View at Publisher · View at Google Scholar
  70. B. T. J. Hennessy, K. M. Timms, M. S. Carey et al., “Somatic mutations in BRCA1 and BRCA2could expand the number of patients that benefit from poly (ADP ribose) polymerase inhibitors in ovarian cancer,” Journal of Clinical Oncology, vol. 28, no. 22, pp. 3570–3576, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. P. A. Russell, P. D. Pharoah, K. de Foy et al., “Frequent loss of BRCA1 mRNA and protein expression in sporadic ovarian cancers,” International Journal of Cancer, vol. 87, no. 3, pp. 317–321, 2000. View at Publisher · View at Google Scholar
  72. R. L. Baldwin, E. Nemeth, H. Tran et al., “BRCA1 promoter region hypermethylation in ovarian carcinoma: a population-based study,” Cancer Research, vol. 60, no. 19, pp. 5329–5333, 2000. View at Google Scholar · View at Scopus
  73. J. W. Chiang, B. Y. Karlan, L. Cass, and R. L. Baldwin, “BRCA1 promoter methylation predicts adverse ovarian cancer prognosis,” Gynecologic Oncology, vol. 101, no. 3, pp. 403–410, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. M. W. Beckmann, F. Picard, H. X. An et al., “Clinical impact of detection of loss of heterozygosity of BRCA1 and BRCA2 markers in sporadic breast cancer,” British Journal of Cancer, vol. 73, no. 10, pp. 1220–1226, 1996. View at Publisher · View at Google Scholar · View at Scopus
  75. D. J. Gallagher, J. A. Konner, K. M. Bell-McGuinn et al., “Survival in epithelial ovarian cancer: a multivariate analysis incorporating BRCA mutation status and platinum sensitivity,” Annals of Oncology, vol. 22, no. 5, pp. 1127–1132, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Kwa, S. Edwards, A. Downey et al., “Ovarian cancer in BRCA mutation carriers: improved outcome after intraperitoneal (IP) cisplatin,” Annals of Surgical Oncology, vol. 21, no. 5, pp. 1468–1473, 2014. View at Google Scholar
  77. S. F. Adams, E. B. Marsh, W. Elmasri et al., “A high response rate to liposomal doxorubicin is seen among women with BRCA mutations treated for recurrent epithelial ovarian cancer,” Gynecologic Oncology, vol. 123, no. 3, pp. 486–491, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. S. B. Kaye, J. Lubinski, U. Matulonis et al., “Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer,” Journal of Clinical Oncology, vol. 30, no. 4, pp. 372–379, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. T. Safra, L. Borgato, M. O. Nicoletto et al., “BRCA mutation status and determinant of outcome in women with recurrent epithelial ovarian cancer treated with pegylated liposomal doxorubicin,” Molecular Cancer Therapeutics, vol. 10, no. 10, pp. 2000–2007, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. D. J. Stewart, “Mechanisms of resistance to cisplatin and carboplatin,” Critical Reviews in Oncology/Hematology, vol. 63, no. 1, pp. 12–31, 2007. View at Publisher · View at Google Scholar · View at Scopus
  81. H. Farmer, H. McCabe, C. J. Lord et al., “Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy,” Nature, vol. 434, no. 7035, pp. 917–921, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. D. D'Amours, S. Desnoyers, I. D'Silva, and G. G. Poirier, “Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions,” Biochemical Journal, vol. 342, part 2, pp. 249–268, 1999. View at Publisher · View at Google Scholar · View at Scopus
  83. H. E. Bryant, N. Schultz, H. D. Thomas et al., “Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase,” Nature, vol. 434, no. 7035, pp. 913–917, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. M. W. Audeh, J. Carmichael, R. T. Penson et al., “Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial,” The Lancet, vol. 376, no. 9737, pp. 245–251, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. J. A. Ledermann, P. Harter, C. Gourley et al., “Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer (SOC) and a BRCA mutation (BRCAm),” in Proceedings of the ASCO Annual Meeting, 2013.
  86. J. Ledermann, P. Harter, C. Gourley et al., “Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer,” The New England Journal of Medicine, vol. 366, no. 15, pp. 1382–1392, 2012. View at Publisher · View at Google Scholar · View at Scopus
  87. A. M. Oza, D. Cibula, A. Oaknin et al., “Olaparib plus paclitaxel plus carboplatin (P/C) followed by olaparib maintenance treatment in patients (pts) with platinum-sensitive recurrent serous ovarian cancer (PSR SOC): a randomized, open-label phase II study,” Journal of Clinical Oncology (Meeting Abstracts), vol. 30, no. 15, supplement, article 5001, 2012, ASCO Annual Meeting Abstracts. View at Google Scholar
  88. K. L. Bolton, G. Chenevix-Trench, C. Goh et al., “Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer,” Journal of the American Medical Association, vol. 307, no. 4, pp. 382–390, 2012. View at Publisher · View at Google Scholar · View at Scopus
  89. T. Safra, W. C. Lai, L. Borgato et al., “BRCA mutations and outcome in epithelial ovarian cancer (EOC): experience in ethnically diverse groups,” Annals of Oncology, vol. 24, supplement 8, pp. viii63–viii68, 2013. View at Google Scholar
  90. J. Liu, M. C. Cristea, P. Frankel et al., “Clinical characteristics and outcomes of BRCA-associated ovarian cancer: genotype and survival,” Cancer Genetics, vol. 205, no. 1-2, pp. 34–41, 2012. View at Publisher · View at Google Scholar · View at Scopus
  91. D. Lorusso, F. Cirillo, M. Mancini et al., “The different impact of BRCA mutations on the survival of epithelial ovarian cancer patients: a retrospective single-center experience,” Oncology, vol. 85, no. 2, pp. 122–127, 2013. View at Publisher · View at Google Scholar · View at Scopus
  92. D. M. Hyman, Q. Zhou, A. Iasonos et al., “Improved survival for BRCA2-associated serous ovarian cancer compared with both BRCA-negative and BRCA1-associated serous ovarian cancer,” Cancer, vol. 118, no. 15, pp. 3703–3709, 2012. View at Publisher · View at Google Scholar · View at Scopus
  93. D. M. Hyman, K. C. Long, E. J. Tanner et al., “Outcomes of primary surgical cytoreduction in patients with BRCA-associated high-grade serous ovarian carcinoma,” Gynecologic Oncology, vol. 126, no. 2, pp. 224–228, 2012. View at Publisher · View at Google Scholar · View at Scopus
  94. U. E. Martinez-Outschoorn, R. Balliet, Z. Lin et al., “BRCA1 mutations drive oxidative stress and glycolysis in the tumor microenvironment: implications for breast cancer prevention with antioxidant therapies,” Cell Cycle, vol. 11, no. 23, pp. 4402–4413, 2012. View at Publisher · View at Google Scholar · View at Scopus
  95. AA. Arbini, F. Guerra, M. Greco et al., “Mitochondrial DNA depletion sensitizes cancer cells to PARP inhibitors by translational and post-translational repression of BRCA2,” Oncogenesis, vol. 2, article e82, 2013. View at Google Scholar
  96. S. Chen and G. Parmigiani, “Meta-analysis of BRCA1 and BRCA2 penetrance,” Journal of Clinical Oncology, vol. 25, no. 11, pp. 1329–1333, 2007. View at Publisher · View at Google Scholar · View at Scopus
  97. A. Antoniou, P. D. Pharoah, S. Narod 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,” The American Journal of Human Genetics, vol. 72, no. 5, pp. 1117–1130, 2003. View at Publisher · View at Google Scholar · View at Scopus
  98. H. A. Risch, J. R. McLaughlin, D. E. C. Cole et al., “Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer,” American Journal of Human Genetics, vol. 68, no. 3, pp. 700–710, 2001. View at Publisher · View at Google Scholar · View at Scopus
  99. M. Sekine, H. Nagata, S. Tsuji et al., “Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population,” Clinical Cancer Research, vol. 7, no. 10, pp. 3144–3150, 2001. View at Google Scholar · View at Scopus
  100. NCCN Guideline Version 4, “NCCN NCCN: Genetic/Familiar High Risk Assessment: breast and Ovarian,” in NCCN Clinical Practice Guidelines in Oncology, 2003. View at Google Scholar
  101. A. Gadducci, C. Sergiampietri, and R. Tana, “Alternatives to risk-reducing surgery for ovarian cancer,” Annals of Oncology, vol. 24, supplement 8, pp. viii47–viii53, 2013. View at Publisher · View at Google Scholar
  102. W. Burke, M. Daly, J. Garber et al., “Recommendations for follow-up care of individuals with an inherited predisposition to cancer: II. BRCA1 and BRCA2,” The Journal of the American Medical Association, vol. 277, no. 12, pp. 997–1003, 1997. View at Publisher · View at Google Scholar · View at Scopus
  103. S. S. Buys, E. Partridge, A. Black et al., “Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening randomized controlled trial,” Journal of the American Medical Association, vol. 305, no. 22, pp. 2295–2303, 2011. View at Publisher · View at Google Scholar · View at Scopus
  104. H. Kobayashi, Y. Yamada, T. Sado et al., “A randomized study of screening for ovarian cancer: a multicenter study in Japan,” International Journal of Gynecological Cancer, vol. 18, no. 3, pp. 414–420, 2008. View at Publisher · View at Google Scholar · View at Scopus
  105. U. Menon, A. Gentry-Maharaj, R. Hallett et al., “Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS),” The Lancet Oncology, vol. 10, no. 4, pp. 327–340, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. D. L. Stan, L. T. Shuster, M. J. Wick, C. L. Swanson, S. Pruthi, and J. N. Bakkum-Gamez, “Challenging and complex decisions in the management of the BRCA mutation carrier,” Journal of Women's Health, vol. 22, no. 10, pp. 825–834, 2013. View at Google Scholar
  107. A. Finch, G. Evans, and S. A. Narod, “BRCA carriers, prophylactic salpingo-oophorectomy and menopause: clinical management considerations and recommendations,” Women's Health, vol. 8, no. 5, pp. 543–555, 2012. View at Publisher · View at Google Scholar · View at Scopus
  108. A. Finch, M. Beiner, J. Lubinski et al., “Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation,” The Journal of the American Medical Association, vol. 296, no. 2, pp. 185–192, 2006. View at Publisher · View at Google Scholar
  109. M. J. Casey, C. Synder, C. Bewtra, S. A. Narod, P. Watson, and H. T. Lynch, “Intra-abdominal carcinomatosis after prophylactic oophorectomy in women of hereditary breast ovarian cancer syndrome kindreds associated with BRCA1 and BRCA2 mutations,” Gynecologic Oncology, vol. 97, no. 2, pp. 457–467, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. H. W. Lafferty, R. Angioli, J. Rudolph, and M. A. Penalver, “Ovarian remnant syndrome: experience at Jackson Memorial Hospital, University of Miami, 1985 through 1993,” American Journal of Obstetrics and Gynecology, vol. 174, no. 2, pp. 641–645, 1996. View at Publisher · View at Google Scholar · View at Scopus
  111. N. D. Kauff and R. R. Barakat, “Risk-reducing salpingo-oophorectomy in patients with germline mutations in BRCA1 or BRCA2,” Journal of Clinical Oncology, vol. 25, no. 20, pp. 2921–2927, 2007. View at Publisher · View at Google Scholar · View at Scopus
  112. M. E. Beiner, A. Finch, B. Rosen et al., “The risk of endometrial cancer in women with BRCA1 and BRCA2 mutations: a prospective study,” Gynecologic Oncology, vol. 104, no. 1, pp. 7–10, 2007. View at Publisher · View at Google Scholar · View at Scopus
  113. O. Lavie, A. Ben-Arie, Y. Segev et al., “BRCA germline mutations in women with uterine serous carcinoma—still a debate,” International Journal of Gynecological Cancer, vol. 20, no. 9, pp. 1531–1534, 2010. View at Google Scholar · View at Scopus
  114. R. J. Kurman, “Origin and molecular pathogenesis of ovarian high-grade serous carcinoma,” Annals of Oncology, vol. 24, supplement 10, pp. x16–x21, 2013. View at Publisher · View at Google Scholar
  115. E. Leblanc, F. Narducci, I. Farre et al., “Radical fimbriectomy: a reasonable temporary risk-reducing surgery for selected women with a germ line mutation of BRCA 1 or 2 genes? Rationale and preliminary development,” Gynecologic Oncology, vol. 121, no. 3, pp. 472–476, 2011. View at Publisher · View at Google Scholar · View at Scopus
  116. P. F. Escobar, D. C. Starks, A. N. Fader, M. Barber, and L. Rojas-Espalliat, “Single-port risk-reducing salpingo-oophorectomy with and without hysterectomy: surgical outcomes and learning curve analysis,” Gynecologic Oncology, vol. 119, no. 1, pp. 43–47, 2010. View at Publisher · View at Google Scholar · View at Scopus
  117. A. Finch, P. Shaw, B. Rosen, J. Murphy, S. A. Narod, and T. J. Colgan, “Clinical and pathologic findings of prophylactic salpingo-oophorectomies in 159 BRCA1 and BRCA2 carriers,” Gynecologic Oncology, vol. 100, no. 1, pp. 58–64, 2006. View at Publisher · View at Google Scholar · View at Scopus
  118. J. E. Hirst, G. B. Gard, K. Mcillroy, D. Nevell, and M. Field, “High rates of occult fallopian tube cancer diagnosed at prophylactic bilateral salpingo-oophorectomy,” International Journal of Gynecological Cancer, vol. 19, no. 5, pp. 826–829, 2009. View at Publisher · View at Google Scholar · View at Scopus
  119. R. I. Olivier, M. aan Beurden, M. A. C. Lubsen et al., “Clinical outcome of prophylactic oophorectomy in BRCA1/BRCA2 mutation carriers and events during follow-up,” British Journal of Cancer, vol. 90, no. 8, pp. 1492–1497, 2004. View at Publisher · View at Google Scholar · View at Scopus