Gynecological Care and Prevention of Gynecological Malignancies in BRCA1 and BRCA2 Mutation Carriers

Czech version

Authors: Michal Zikán
Authors‘ workplace: Onkogynekologické centrum, Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze
Published in: Klin Onkol 2016; 29(Supplementum 1): 22-30
Category: Review
doi: https://doi.org/10.14735/amko2016S22

Overview

This paper summarizes the current knowledge of gynecological care aspects in women with inherited predisposition to breast and ovarian cancer, i.e. BRCA1 and BRCA2 mutation carriers, and proposes guidelines for furher management of these women, addressing follow-up recommendations, prophylactic surgery indications and preimplantation genetic conseling. It evaluates cancer risk and severity of ovarian cancer in particular with regards to its high mortality resulting from aggressive biological behavior of the tumor and late detection rates. BRCA-positive women should be enrolled in prevention programs including carefull surveillance, prophylactic surgery or pre-implantation genetic counseling. Follow-up care consists of gynecological examination, expert oncogynecological ultrasound and tumor marker CA125 examination every six months. However, the most effective strategy for mortality reduction in ovarian cancer is prophylactic surgery – salpingo-oophorectomy (and hysterectomy). The optimal age for surgery is between 35 to 40 years. Prophylactic salpingo-oophorectomy performed in premenopausal women was proved to reduce the risk of ovarian as well as breast cancer. Symptoms of estrogen deficiency after prophylactic surgery can be suppressed by administration of hormone replacement therapy without increasing the risk of breast cancer. Preimplantation genetic diagnosis is an effective way to prevent the trans-mission of hereditary predisposition to the next generation. The management of patients with hereditary suspceptibility to ovarian cancer should be confined to specialized centres.

Key words:
hereditary breast and ovarian cancer syndrome – ovarian neoplasms – BRCA1 gene – BRCA2 gene

The author declares he has no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
14. 7. 2015

Accepted:
3. 9. 2015

Sources

1. 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(3): 700– 710.

2. King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003; 302(5645): 643– 646.

3. Zikan M. Hereditární syndromy. In: Cibula D, Petruželka L(eds). Onkogynekologie. Praha: Grada 2009: 614.

4. Bolton KL, Chenevix-Trench G, Goh C et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA 2012; 307(4): 382– 390. doi: 10.1001/ jama.2012.20.

5. Plevova P, Novotny J, Petrakova K et al. Hereditary breast and ovarian cancer syndrome. Klin Onkol 2009; 22 (Suppl): S8– S11.

6. Hogg R, Friedlander M. Biology of epithelial ovarian cancer: implications for screening women at high genetic risk. J Clin Oncol 2004; 22(7): 1315– 1327.

7. Buys SS, Partridge E, Black A 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: 10.1001/ jama.2011.766.

8. Buys SS, Partridge E, Greene MH et al. Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial: findings from the initial screen of a randomized trial. Am J Obstet Gynecol 2005; 193(5): 1630– 1639.

9. Kobayashi H, Yamada Y, Sado T et al. A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer 2008; 18(3): 414– 420.

10. Menon U, Gentry-Maharaj A, Hallett R 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). Lancet Oncol 2009; 10(4): 327– 340. doi: 10.1016/ S1470-2045(09)70026-9.

11. Menon U, Griffin M, Gentry-Maharaj A. Ovarian cancer screening – current status, future directions. Gynecol Oncol 2014; 132(2): 490– 495. doi: 10.1016/ j.ygyno.2013.11.030.

12. Hermsen BB, Olivier RI, Verheijen RH et al. No efficacy of annual gynaecological screening in BRCA1/ 2 mutation carriers; an observational follow-up study. Br J Cancer 2007; 96(9): 1335– 1342.

13. Stirling D, Evans DG, Pichert G et al. Screening for familial ovarian cancer: failure of current protocols to detect ovarian cancer at an early stage according to the international Federation of gynecology and obstetrics system. J Clin Oncol 2005; 23(24): 5588– 5596.

14. Rosenthal AN, Fraser L, Manchanda R et al. Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule. J Clin Oncol 2013; 31(1): 49– 57. doi: 10.1200/ JCO.2011.39.7638.

15. Skates SJ, Mai P, Horick NK et al. Large prospective study of ovarian cancer screening in high-risk women: CA125 cut-point defined by menopausal status. Cancer Prev Res 2011; 4(9): 1401– 1408. doi: 10.1158/ 1940-6207.CAPR-10-0402.

16. Greene MH, Piedmonte M, Alberts D et al. A prospective study of risk-reducing salpingo-oophorectomy and longitudinal CA-125 screening among women at increased genetic risk of ovarian cancer: design and baseline characteristics: a Gynecologic Oncology Group study. Cancer Epidemiol Biomarkers Prev 2008; 17(3): 594– 604. doi: 10.1158/ 1055-9965.EPI-07-2703.

17. Van Calster B, Timmerman D, Bourne T et al. Discrimination between benign and malignant adnexal masses by specialist ultrasound examination versus serum CA-125.J Natl Cancer Inst 2007; 99(22): 1706– 1714.

18. Valentin L, Jurkovic D, Van Calster B et al. Adding a single CA 125 measurement to ultrasound imaging performed by an experienced examiner does not improve preoperative discrimination between benign and malignant adnexal masses. Ultrasound Obstet Gynecol 2009; 34(3): 345– 354. doi: 10.1002/ uog.6415.

19. Antoniou AC, Rookus M, Andrieu N et al. Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: results from the International BRCA1/ 2 Carrier Cohort Study. Cancer Epidemiol Biomarkers Prev 2009; 18(2): 601– 610. doi: 10.1158/ 1055-9965.EPI-08-0546.

20. McLaughlin JR, Risch HA, Lubinski J et al. Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study. Lancet Oncol 2007; 8(1): 26– 34.

21. Modan B, Hartge P, Hirsh-Yechezkel G et al. Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. N Engl J Med 2001; 345(4): 235– 240.

22. Narod SA, Risch H, Moslehi R et al. Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med 1998; 339(7): 424– 428.

23. Narod SA, Dube MP, Klijn J et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 2002; 94(23): 1773– 1779.

24. Cibula D, Zikan M, Dusek L et al. Oral contraceptives and risk of ovarian and breast cancers in BRCA mutation carriers: a meta-analysis. Export Rev Anticancer Ther 2011; 11(8): 1197– 1207. doi: 10.1586/ era.11.38.

25. Antoniou AC, Shenton A, Maher ER et al. Parity and breast cancer risk among BRCA1 and BRCA2 mutation carriers. Breast Cancer Res 2006; 8(6): R72.

26. Cullinane CA, Lubinski J, Neuhausen SL et al. Effect of pregnancy as a risk factor for breast cancer in BRCA1/ BRCA2 mutation carriers. Int J Cancer 2005; 117(6): 988– 991.

27. Kotsopoulos J, Lubinski J, Salmena L et al. Breastfeeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res 2012; 14(2): R42.

28. Vashi R, Hooley R, Butler R et al. Breast imaging of the pregnant and lactating patient: physiologic changes and common benign entities. AJR Am J Roentgenol 2013; 200(2): 329– 336. doi: 10.2214/ AJR.12.9845.

29. Vashi R, Hooley R, Butler R et al. Breast imaging of the pregnant and lactating patient: imaging modalities and pregnancy-associated breast cancer. AJR Am J Roentgenol 2013; 200(2): 321– 328.

30. Kotsopoulos J, Librach CL, Lubinski J et al. Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations: a case control study. Cancer Causes Control 2008; 19(10): 1111– 1119. doi: 10.1007/ s10552-008-9175-0.

31. Norquist BM, Garcia RL, Allison KH et al. The molecular pathogenesis of hereditary ovarian carcinoma: alterations in the tubal epithelium of women with BRCA1 and BRCA2 mutations. Cancer 2010; 116(22): 5261– 5271. doi: 10.1002/ cncr.25439.

32. Kauff ND, Domchek SM, Friebel TM et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol 2008; 26(8): 1331– 1337.

33. Rebbeck TR, Lynch HT, Neuhausen SL et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002; 346(21): 1616– 1622.

34. Mitrunen K, Hirvonen A. Molecular epidemiology of sporadic breast cancer. The role of polymorphic genes involved in oestrogen biosynthesis and metabolism. Mutat Res 2003; 544(1): 9– 41.

35. Heemskerk-Gerritsen BA, Seynaeve C, van Asperen CJet al. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/ 2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst 2015; 107(9): pii: djv217. doi: 10.1093/ jnci/ djv217.

36. Domchek SM, Friebel TM, Neuhausen SL et al. Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study. Lancet Oncol 2006; 7(3): 223– 229.

37. Ford D, Easton DF, Stratton M et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 1998; 62(3): 676– 689.

38. Struewing JP, Hartge P, Wacholder S et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 1997; 336(20): 1401– 1408.

39. Cibula D, Widschwendter M, Majek O et al. Tubal ligation and the risk of ovarian cancer: review and meta-analysis. Hum Reprod Update 2011; 17(1): 55– 67. doi: 10.1093/ humupd/ dmq030.

40. Beiner ME, Finch A, Rosen B et al. The risk of endometrial cancer in women with BRCA1 and BRCA2 mutations: a prospective study. Gynecol Oncol 2007; 104(1): 7– 10.

41. Schorge JO, Modesitt SC, Coleman RL et al. SGO White Paper on ovarian cancer: etiology, screening and surveillance. Gynecol Oncol 2010; 119(1): 7– 17. doi: 10.1016/ j.ygyno.2010.06.003.

42. Radosa JC, Meyberg-Solomayer G, Kastl C et al. Influences of different hysterectomy techniques on patients’ postoperative sexual function and quality of life. J Sex Med 2014; 11: 2342– 2350. doi: 10.1111/ jsm.12623.

43. Pauls RN. Impact of gynecological surgery on female sexual function. Int J Impot Res 2010; 22(2): 105– 114. doi: 10.1038/ ijir.2009.63.

44. Duru C, Jha S, Lashen H. Urodynamic outcomes after hysterectomy for benign conditions: a systematic review and meta-analysis. Obstet Gynecol Surv 2012; 67(1): 45– 54. doi: 10.1097/ OGX.0b013e318240aa28.

45. de Jong D, Rosen BF, Finch A et al. Low incidence of ovarian cancer established by prophylactic hysterectomy and BSO in patients with BRCA1 and BRCA2 mutations. IGCS 2008. Bangkok 2008.

46. Kurman RJ, Shih IE M. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 2010; 34(3): 433– 443. doi: 10.1097/ PAS.0b013e3181cf3d79.

47. Falconer H, Yin L, Gronberg H et al. Ovarian cancer risk after salpingectomy: a nationwide population-based study. J Natl Cancer Inst 2015; 107(2): pii: dju410. doi: 10.1093/ jnci/ dju410.

48. Powell CB, Chen LM, McLennan J et al. Risk-reducing salpingo-oophorectomy (RrSO) in BRCA mutation carriers: experience with a consecutive series of 111 patients using a standardized surgical-pathological protocol. Int J Gynecol Cancer 2011; 21(5): 846– 851. doi: 10.1097/ IGC.0b013e31821bc7e3.

49. Manchanda R, Abdelraheim A, Johnson M et al. Outcome of risk-reducing salpingo-oophorectomy in BRCA carriers and women of unknown mutation status. BJOG 2011; 118(7): 814– 824.

50. Madalinska JB, Hollenstein J, Bleiker E et al. Quality-of-life effects of prophylactic salpingo-oophorectomy versus gynecologic screening among women at increased risk of hereditary ovarian cancer. J Clin Oncol 2005; 23(28): 6890– 6898.

51. Holmberg L, Anderson H. HABITS (hormonal replacement therapy after breast cancer – is it safe?), a randomized comparison: trial stopped. Lancet 2004; 363(9407): 453– 455.

52. Bundred NJ, Kenemans P, Yip CH et al. Tibolone increases bone mineral density but also relapse in breast cancer survivors: LIBERATE trial bone substudy. Breast Cancer Res 2012; 14(1): R13.

53. Kenemans P, Bundred NJ, Foidart JM et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomized, non-inferiority trial. Lancet Oncol 2009; 10(2): 135– 146. doi: 10.1016/ S1470-2045(08)70341-3.

54. Chlebowski RT, Kuller LH, Prentice RL et al. Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med 2009; 360(6): 573– 587. doi: 10.1056/ NEJMoa0807684.

55. Rebbeck TR, Friebel T, Wagner T et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2005; 23(31): 7804– 7810.

56. Medeiros F, Muto MG, Lee Y et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 2006; 30(2): 230– 236.

57. Quinn GP, Vadaparampil ST, Bower B et al. Decisions and ethical issues among BRCA carriers and the use of preimplantation genetic diagnosis. Minerva Med 2009; 100(5): 371– 383.

58. Hüttelova R, Kleibl Z, Rezatova J et al. Prerequisites for preimplantation genetic diagnosis (PGD) in carriers of mutations responsible for hereditary cancers. Klin Onkol 2009; 22 (Suppl): S69– S74.

59. Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSs): a review. Hum Reprod Update 2002; 8(6): 559– 577.

60. McArthur SJ, Leigh D, Marshall JT et al. Pregnancies and live births after trophectoderm biopsy and preimplantation genetic testing of human blastocysts. Fertil Steril 2005; 84(6): 1628– 1636.