Managing a woman with &lt;i&gt;BRCA&lt;/i&gt; mutations? Shared decision-making is key

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doi:10.12788/jfp.0003

Applied Evidence

Managing a woman with BRCA mutations? Shared decision-making is key

J Fam Pract. 2020 June;69(5):237-243 | 10.12788/jfp.0003

By

Sarina Schrager, MD, MS

Emily Torell, MD

Kate Ledford, DO, MPH

Mae Elezaby, MD

Lisa Barroleit, MD

Elizabeth Sadowski, MD

A collaborative assessment of options and trade-offs—perhaps using visual decision aids—can help.

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PRACTICE RECOMMENDATIONS

› Recommend genetic screening for the BRCA mutation if a patient’s family history includes a breast cancer diagnosis before age 50, occurrences of both breast and ovarian cancers, or other suggestive features. C

› Advise women with the BRCA gene to return for a clinical breast exam every 6 to 12 months starting at age 25, and to start radiologic screening at age 30. C

› Consider recommending bilateral salpingo-oophorectomy to prevent ovarian cancer in women 35 to 40 years of age with a BRCA1 mutation who have completed childbearing. C

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

References

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14. Lakhani SR, Manek S, Penault-Llorca F, et al. Pathology of ovarian cancers in BRCA1 and BRCA2 carriers. Clin Cancer Res. 2004;10:2473-2481.

15. Kurian AW. BRCA1 and BRCA2 mutations across race and ethnicity: distribution and clinical implications. Curr Opin Obstet Gynecol. 2010;22:72-78.

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19. Yerushalmi R, Rizel S, Zoref D, et al. A dedicated follow-up clinic for BRCA mutation carriers. Isr Med Assoc J. 2016;18:549-552.

20. Pichert G, Jacobs C, Jacobs I, et al. Novel one-stop multidisciplinary follow-up clinic significantly improves cancer risk management in BRCA1/2 carriers. Fam Cancer. 2010;9:313-319.

21. Owens DK, Davidson KW, Krist AH, et al; US Preventive Services Task Force. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2019;322:652-665.

22. Evans D, Eccles D, Rahman N, et al. A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO. J Med Genet. 2004;41:474-480.

23. Bellcross CA, Lemke AA, Pape LS, et al. Evaluation of a breast/ovarian cancer genetics referral screening tool in a mammography population. Genet Med. 2009;11:783-789.

24. Hoskins KF, Zwaagstra A, Ranz M. Validation of a tool for identifying women at high risk for hereditary breast cancer in population based screening. Cancer. 2006;107:1769-1776.

25. Gilpin CA, Carson N, Hunter AG. A preliminary validation of a family history assessment form to select women at risk for breast or ovarian cancer for referral to a genetics center. Clin Genet. 2000;58:299-308.

26. Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin No 182: Hereditary Breast and Ovarian Cancer Syndrome. Obstet Gynecol. 2017;130:e110-e126.

27. Paluch-Shimon S, Cardoso F, Sessa C, et al. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol. 2016;27(suppl 5):v103-v110.

28. National Comprehensive Cancer Network. Genetic/familial high-risk assessment: breast and ovarian. 2019. NCCN Clinical Practice Guidelines in Oncology. www2.tri-kobe.org/nccn/guideline/gynecological/english/genetic_familial.pdf. Accessed May 22, 2020.

29. Phillips KA, Milne RL, Rookus MA, et al. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2013;31:3091-3099.

30. Foulkes WD, Goffin J, Brunet JS, et al. Tamoxifen may be an effective adjuvant treatment for BRCA1-related breast cancer irrespective of estrogen receptor status. J Natl Cancer Inst. 2002;94:1504-1506.

31. Gronwald J, Tung N, Foulkes WD, et al. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer. 2006;118:2281-2284.

32. Ludwig KK, Neuner J, Butler A, et al. Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers, a systematic review. Am J Surgery. 2016;212:660-669.

33. Bougie O, Weberpals JI. Clinical considerations of BRCA1- and BRCA2-mutation carriers: a review. Int J Surg Oncol. 2011;2011:374012.

34. Rosenthal AN, Fraser LSM, Philpott S, et al. Evidence of stage shift in women diagnosed with ovarian cancer during phase II of the United Kingdom Familial Ovarian Cancer Screening Study. J Clin Oncol. 2017;35:1411-1420.

35. Skates SJ, Greene MH, Buys SS, et al. Early detection of ovarian cancer using the Risk of Ovarian Cancer Algorithm with frequent CA125 testing in women at increased familial risk—combined results from two screening trials. Clin Cancer Res. 2017;23:3628-3637.

36. Daly MB, Pilarski R, Berry M, et al. NCCN guidelines insights: genetic/familial high-risk assessment: breast and ovarian, version 2.2017. J Natl Compr Canc Netw. 2017;15:9-20.

37. Grossman DC, Curry SJ, Owens DK, et al. Screening for ovarian cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:588-594.

38. Marchetti C, De Felice F, Palaia I, et al. Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all cause mortality in BRCA 1 and BRCA 2 mutation carriers. BMC Womens Health. 2014;14:150.

39. Nelson HD, Pappas M, Zakher B, et al. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the US Preventive Services Task Force recommendation. Ann Intern Med. 2014;160:255-266.

40. Parker WH, Feskanich D, Broder MS, et al. Long-term mortality associated with oophorectomy compared with ovarian conservation in the nurses’ health study. Obstet Gynecol. 2013;121:709-716.

41. Faubion SS, Kuhle CL, Shuster LT, et al. Long-term health consequences of premature or early menopause and considerations for management. Climacteric. 2015;18:483-491.

42. Menon U, Karpinskyj C, Gentry-Maharaj A. Ovarian cancer prevention and screening. Obstet Gynecol. 2018;131:909-927.

43. Crum CP, Drapkin R, Miron A, et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol. 2007;19:3-9.

44. Kwon JS, Tinker A, Pansegrau G, et al. Prophylactic salpingectomy and delayed oophorectomy as an alternative for BRCA mutation carriers. Obstet Gynecol. 2013;121:14-24.

45. Holman LL, Friedman S, Daniels MS, et al. Acceptability of prophylactic salpingectomy with delayed oophorectomy as risk-reducing surgery among BRCA mutation carriers. Gynecol Oncol. 2014;133:283-286.

46. MD Anderson Cancer Center. Prophylactic salpingectomy with delayed oophorectomy, risk-reducing salpingo-oophorectomy, and ovarian cancer screening among BRCA mutation carriers: a proof-of-concept study. www.mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2013-0340.html. Accessed May 22, 2020.

47. Iodice S, Barile M, Rotmensz N, et al. Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. Eur J Cancer. 2010;46:2275-2284.

48. Moorman PG, Havrilesky LJ, Gierisch JM, 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;31:4188-4198.

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50. Haile RW, Thomas DC, McGuire V, et al. BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev. 2006;15:1863-1870.

51. Lee E, Ma H, McKean-Cowdin R, et al. Effect of reproductive factors and oral contraceptives on breast cancer risk in BRCA1/2 mutation carriers and noncarriers: results from a population-based study. Cancer Epidemiol Biomarkers Prev. 2008;17:3170-3178.

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CASE

Sara T* recently moved back to the area to be closer to her family. The 34-year-old patient visited our office to discuss the benefits and potential risks of genetic counseling. She explained that her aunt had just died at age 64 of ovarian cancer. Also, her maternal cousin had been diagnosed at age 42 with breast cancer, and her maternal grandmother had died at age 45 of an unknown “female cancer.” She was scared to find out if she had high-risk genes because she felt it would change her life forever. However, if she ignored the issue, she thought she might worry too much.

We discussed the implications of a positive result, such as having to live with the knowledge and to make decisions about potential screening and risk-reducing surgery. On the other hand, not knowing could allow for the undetected growth of cancer that might otherwise be mitigated to some degree if she knew her risk status and pursued an aggressive screening program.

We worked with Ms. T to map out her next steps.

*The patient’s name has been changed to protect her identity.

Breast cancer is the most commonly diagnosed cancer in women worldwide, representing nearly one-quarter of all female cancer diagnoses in 2018.¹ It is the second-leading cause of cancer death in women in developed nations and the leading cause of cancer death in women in developing nations.¹ In the United States, 1 in 8 women will develop breast cancer in her lifetime.² By comparison, the rate of ovarian cancer is much lower, with a lifetime prevalence of 1 in 70 to 80 women.^3,4 Although ovarian cancer is less common than breast cancer, its associated mortality is high, and most cases are discovered at advanced stages.

The outsized threat of BRCA mutations. It is estimated that 5% to 10% of all breast cancers are hereditary, with 80% of these attributable to BRCA1 (45%) and BRCA2 (35%).⁵ These autosomal dominant mutations occur at the germline level, within the egg or sperm, and are therefore incorporated into the DNA of every cell and passed from one generation to the next. Families with BRCA mutations have much higher lifetime rates of cancer. The lifetime risk of breast cancer due to BRCA mutations is estimated at > 80% (BRCA1) and 45% (BRCA2).⁵BRCA mutations account for between 10% and 18% of all ovarian cancers⁶ and convey a lifetime risk of 40% (BRCA1) and 15% (BRCA2) to carriers.⁵

USPSTF now also recommends BRCA1/2 screening for any woman with a family history of tubal or peritoneal cancer.

Male BRCA carriers have a lifetime breast cancer risk of 1% to 5% with BRCA1 and 5% to 10% with BRCA2,^7,8 compared with about 1:1000 lifetime incidence in the unselected male population. Male carriers are also at risk for more aggressive prostate cancers.^7,8

Continue to: Certain populatiosn carry undue burden of BRCA-related disease