Udayana University, Indonesia
Udayana University, Indonesia
* Corresponding author

Article Main Content

Ovarian cancer is a diverse disease with several cellular subtypes, the most common of which are high-grade serous ovarian cancer (HGSOC). Ovarian cancer is still primarily treated with chemotherapy and surgery. Recent advances in the hereditary understanding of this disease have revealed that the BRCA gene plays an important role. While only a small percentage of HGSOC patients will have a germline BRCA mutation, many more will have tumor genetic aberrations within BRCA or other homologous recombination proteins. Improved preventative measures and therapeutic development have resulted from genetic screening for these BRCA mutations. This review focuses on BRCA mutations and their relationship to the development of ovarian cancer, as well as future therapeutic targets.

References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics. CA Cancer J Clin. 2021; 71(1): 7-33.
    DOI  |   Google Scholar
  2. Wright AA, Cronin A, Milne DE, Bookman MA, Burger RA, Cohn DE, et al. Use and Effectiveness of Intraperitoneal Chemotherapy for Treatment of Ovarian Cancer. J Clin Oncol. 2015; 33(26): 2841-2847.
    DOI  |   Google Scholar
  3. Adambekov S, Lopa S, Edwards RP, Lemon L, Wang S, Taylor SE, et al. Survival and recurrence after intraperitoneal chemotherapy use: Retrospective review of ovarian cancer hospital registry data. Cancer Med. 2020; 9(20): 7388-7397.
    DOI  |   Google Scholar
  4. Huertas P. DNA resection in eukaryotes: deciding how to fix the break. Nat Struct Mol Biol. 2010; 17(1): 11-16.
    DOI  |   Google Scholar
  5. Hartlerode AJ, Scully R. Mechanisms of double-strand break repair in somatic mammalian cells. Biochem J. 2009; 423(2): 157-168.
    DOI  |   Google Scholar
  6. Murmann-Konda T, Soni A, Stuschke M, Iliakis G. Analysis of chromatid-break-repair detects a homologous recombination to non-homologous end-joining switch with increasing load of DNA double-strand breaks. Mutat Res Genet Toxicol Environ Mutagen. 2021; 867: 503372.
    DOI  |   Google Scholar
  7. Castro E, Goh C, Olmos D, Saunders E, Leongamornlert D, Tymrakiewicz M, et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol. 2013; 31(14): 1748-1757.
    DOI  |   Google Scholar
  8. Alsop K, Fereday S, Meldrum C, DeFazio A, Emmanuel C, George J, 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. J Clin Oncol. 2012; 30(21): 2654-2663.
    DOI  |   Google Scholar
  9. Lancaster JM, Powell CB, Chen LM, Richardson DL. SGO Clinical Practice Committee. Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol. 2015; 136(1): 3-7.
    DOI  |   Google Scholar
  10. Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2016; 387(10022): 945-956.
    DOI  |   Google Scholar
  11. Desmond A, Kurian AW, Gabree M, Mills MA, Anderson MJ, Kobayashi Y. Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment. JAMA Oncol. 2015; 1(7): 943-951.
    DOI  |   Google Scholar
  12. Robson ME, Bradbury AR, Arun B, Domchek SM, Ford JM, Hampel HL, et al. American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility. J Clin Oncol. 2015; 33(31): 3660-3667.
    DOI  |   Google Scholar
  13. Buys SS, Partridge E, Black A, Johnson CC, Lamerato L, Isaacs C, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011; 305(22): 2295-2303.
    DOI  |   Google Scholar
  14. Eleje GU, Eke AC, Ezebialu IU, Ikechebelu JI, Ugwu EO, Okonkwo OO. Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. Cochrane Database Syst Rev. 2018; 8(8): CD012464.
    DOI  |   Google Scholar
  15. Rebbeck TR. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002; 346(21): 1616-1622.
    DOI  |   Google Scholar
  16. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101(2):80-87. doi:10.1093/jnci/djn442
    DOI  |   Google Scholar
  17. Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002; 346(21): 1609-1615.
    DOI  |   Google Scholar
  18. Falconer H, Yin L, Grönberg H, Altman D. Ovarian cancer risk after salpingectomy: a nationwide population-based study. J Natl Cancer Inst. 2015; 107(2): dju410.
    DOI  |   Google Scholar
  19. Kim SH, Frey MK, Blank SV. Occult tubal carcinoma found at risk reducing salpingectomy in a BRCA1 carrier. Gynecol Oncol Case Rep. 2014; 9: 1-2.
    DOI  |   Google Scholar
  20. Narod SA, Risch H, Moslehi R, Dorum A, Neuhausen S, Olsson H. Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med. 1998; 339(7): 424-428.
    DOI  |   Google Scholar
  21. Moorman PG, Havrilesky LJ, Gierisch JM, Coeytaux RR, Lowery WJ, Peragallo Urrutia R, et al. Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis. J Clin Oncol. 2013; 31(33): 4188-4198.
    DOI  |   Google Scholar
  22. Walsh T, Casadei S, Lee MK. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A. 2011; 108(44): 18032-18037.
    DOI  |   Google Scholar
  23. Tung N, Domchek SM, Stadler Z, Nathanson KL, Couch F, Garber JE, et al. Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol. 2016; 13(9): 581-588.
    DOI  |   Google Scholar
  24. Rubin SC, Benjamin I, Behbakht K, Takahashi H, Morgan MA, LiVolsi VA, et al. Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA1. N Engl J Med. 1996; 335(19): 1413-1416.
    DOI  |   Google Scholar
  25. Kotsopoulos J, Rosen B, Fan I, Moody J, McLaughlin JR, Risch H, et al. Ten-year survival after epithelial ovarian cancer is not associated with BRCA mutation status. Gynecol Oncol. 2016; 140(1): 42-47.
    DOI  |   Google Scholar
  26. Purnell MR, Whish WJ. Novel inhibitors of poly(ADP-ribose) synthetase. Biochem J. 1980; 185(3): 775-777.
    DOI  |   Google Scholar
  27. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009; 361(2): 123-134.
    DOI  |   Google Scholar
  28. Fong PC, Yap TA, Boss DS, Carden CP, Mergui-Roelvink M, Gourley C, et al. Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol. 2010; 28(15): 2512-2519.
    DOI  |   Google Scholar
  29. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012; 366(15): 1382-1392.
    DOI  |   Google Scholar
  30. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014; 15(8): 852-861.
    DOI  |   Google Scholar
  31. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015; 33(3): 244-250.
    DOI  |   Google Scholar
  32. Korpanty G, Timms K, Abkevich V, Carey M, Gutin A, Li Y, et al. Loss of heterozygosity (LOH) as a measure of whole-genome instability in ovarian cancer correlates with clinical outcomes. J Clin Oncol. 2011; 19(15): 5027.
    DOI  |   Google Scholar
  33. Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun JE et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017; 18(1): 75-87.
    DOI  |   Google Scholar
  34. Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, et al. A Phase I-II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clin Cancer Res. 2017; 23(15): 4095-4106.
    DOI  |   Google Scholar
  35. Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016; 375(22): 2154-2164.
    DOI  |   Google Scholar
  36. Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014; 15(11): 1207-1214.
    DOI  |   Google Scholar


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