Current Oncology Reports

, Volume 10, Issue 1, pp 47–53

The clinical management of BRCA1 and BRCA2 mutation carriers



Mutations in the cancer susceptibility genes BRCA1 and BRCA2 are associated with significantly increased risks of breast and ovarian cancer. Fortunately, effective strategies are available to reduce these risks, including genetic testing, which is an important consideration in determining management of patients with a strong family history of cancer. This article reviews the current evidence for risk-reducing strategies in BRCA1 and BRCA2 mutation carriers and outlines future research directions. In particular, screening controversies and current guidelines are discussed, as are issues related to prophylactic mastectomy and oophorectomy.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    King MC, Marks JH, Mandell JB: Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003, 302:643–646.PubMedCrossRefGoogle Scholar
  2. 2.
    Antoniou AC, Pharoah PD, Narod S, et al.: Breast and ovarian cancer risks to carriers of the BRCA 5382insC and 185delAG and BRCA2 6171delT mutations: a combined analysis of 22 population based studies. J Med Genet 2005, 42:602–603.PubMedCrossRefGoogle Scholar
  3. 3.
    Gaarenstroom KN, van der Hiel B, Tollenaar RA, et al.: Efficacy of screening women at high risk of hereditary ovarian cancer: results of an 11-year cohort study. Int J Gynecol Cancer 2006, 16:54–59.PubMedCrossRefGoogle Scholar
  4. 4.
    Oei AL, Massuger LF, Bulten J, et al.: Surveillance of women at high risk for hereditary ovarian cancer is inefficient. Br J Cancer 2006, 94:814–819.PubMedCrossRefGoogle Scholar
  5. 5.
    Olivier RI, Lubsen-Brandsma MA, Verhoef S, et al.: CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer. Gynecol Oncol 2006, 100:20–26.PubMedCrossRefGoogle Scholar
  6. 6.
    Narod SA, Risch H, Moslehi R, et al.: Oral contraceptives and the risk of hereditary ovarian cancer. N Engl J Med 1998, 339:424–428.PubMedCrossRefGoogle Scholar
  7. 7.
    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, 8:26–34.PubMedCrossRefGoogle Scholar
  8. 8.
    Whittemore AS, Balise RR, Pharoah PD, et al.: Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations. Br J Cancer 2004, 91:1911–1915.PubMedCrossRefGoogle Scholar
  9. 9.
    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, 94:1773–1779.PubMedGoogle Scholar
  10. 10.
    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.PubMedCrossRefGoogle Scholar
  11. 11.
    Brohet RM, Goldgar DE, Easton DF, et al.: Oral contraceptives and breast cancer risk in the International BRCA1/2 Carrier Cohort Study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group. J Clin Oncol 2007, [Epub ahead of print].Google Scholar
  12. 12.
    Rebbeck TR, Lynch HT, Neuhausen SL, et al.: Prophylactic oophorectomy in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 2002, 346:1616–1622.PubMedCrossRefGoogle Scholar
  13. 13.
    Kauff ND, Satagopan JM, Robson ME, et al.: Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2002, 346:1609–1615.PubMedCrossRefGoogle Scholar
  14. 14.
    Rutter JL, Wacholder S, Chetrit A, et al.: Gynecologic surgeries and risk of ovarian cancer in women with BRCA1 and BRCA2 Ashkenazi founder mutations: an Israeli population-based case-control study. J Natl Cancer Inst 2003, 95:1072–1078.PubMedCrossRefGoogle Scholar
  15. 15.
    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, 7:223–229.PubMedCrossRefGoogle Scholar
  16. 16.
    Eisen A, Lubinski J, Klijn J, et al.: Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol 2005, 23:7491–7496.PubMedCrossRefGoogle Scholar
  17. 17.
    Kramer JL, Velazquez IA, Chen BE, et al.: Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers. J Clin Oncol 2005, 23:8629–8635.PubMedCrossRefGoogle Scholar
  18. 18.
    Finch A, Beiner M, Lubinski J, et al.: Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. JAMA 2006, 296:185–192.PubMedCrossRefGoogle Scholar
  19. 19.
    Lu K, Garber JE, Cramer DW, et al.: Occult ovarian tumors in women with BRCA1 or BRCA2 mutations undergoing prophylactic oophorectomy. J Clin Oncol 2000, 18:2728–2732.PubMedGoogle Scholar
  20. 20.
    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. J Clin Oncol 2005, 23:7804–7810.PubMedCrossRefGoogle Scholar
  21. 21.
    Anderson GL, Limacher M, Assaf AR, et al.: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized control trial. JAMA 2004, 291:1701–1712.PubMedCrossRefGoogle Scholar
  22. 22.
    Rossouw JE, Anderson GL, Prentice RL, et al.: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002, 288:321–333.PubMedCrossRefGoogle Scholar
  23. 23.
    Kriege M, Brekelmans CT, Boetes C, et al.: Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 2004, 351:427–437.PubMedCrossRefGoogle Scholar
  24. 24.
    Warner E, Plewes DB, Hill KA, et al.: Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 2004, 292:1317–1325.PubMedCrossRefGoogle Scholar
  25. 25.
    Leach MO, Boggis, CR, Dixon AK, et al.: Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 2005, 365:1769–1778.PubMedCrossRefGoogle Scholar
  26. 26.
    Gudmundsdottir K, Ashworth A: The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene 2006, 25:5864–5874.PubMedCrossRefGoogle Scholar
  27. 27.
    Ronkers CM, Erdmann CA, Land CE: Radiation and breast cancer: a review of current evidence. Breast Cancer Res 2005, 7:21–32.CrossRefGoogle Scholar
  28. 28.
    Land CE, Tokunaga M, Koyoma K, et al.: Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950–1990. Radiat Res 2003, 160:707–717.PubMedCrossRefGoogle Scholar
  29. 29.
    Narod SA, Lubinski J, Ghadirian P, et al.: Screening mammography and risk of breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Lancet Oncol 2006, 7:402–406.PubMedCrossRefGoogle Scholar
  30. 30.
    Goldfrank D, Chuai S, Bernstein J, et al.: Effect of mammography on breast cancer risk in women with mutations in BRCA1 or BRCA2. Cancer Epidemiol Biomarkers Prev 2006, 15:2311–2313.PubMedCrossRefGoogle Scholar
  31. 31.
    Andrieu N, Easton D, Chang-Claude J, et al.: Effect of chest x-rays on the risk of breast cancer among BRCA1/2 mutation carriers in the international BRCA1/2 carrier cohort study: a report from the EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators’ Group. J Clin Oncol 2006, 24:3328–3330.CrossRefGoogle Scholar
  32. 32.
    John E, Phipps A, Knight J, et al.: Medical radiation exposure and breast cancer risk: findings from the breast cancer family registry. Int J Cancer 2007, 121:386–394.PubMedCrossRefGoogle Scholar
  33. 33.
    Kauff ND, Domchek SM, Friebel TM, et al.: Multi-center prospective analysis of risk-reducing salpingo-oophorectomy to prevent BRCA-associated breast and ovarian cancer. J Clin Oncol 2007, [In press].Google Scholar
  34. 34.
    Narod SA, Brunet JS, Ghadirian P, et al.: Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Hereditary Breast Cancer Clinical Study Group. Lancet 2000, 356:1876–1881.PubMedCrossRefGoogle Scholar
  35. 35.
    Grunwald J, Tung N, Foulkes WD: Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer 2006, 118:2281–2284.CrossRefGoogle Scholar
  36. 36.
    Fisher B, Costantino JP, Wicherham DL, et al.: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998, 90:1371–1388.PubMedCrossRefGoogle Scholar
  37. 37.
    King MC, Wieand S, Hale K, et al.: Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 2001, 286:2251–2256.PubMedCrossRefGoogle Scholar
  38. 38.
    Vogel VG, Constantino JP, Wickerham DL, et al.: Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: The NSABP study of tamoxifen and raloxifene (STAR) P-2 trial. JAMA 2006, 295:2727–2741.PubMedCrossRefGoogle Scholar
  39. 39.
    Hartmann LC, Schaid DJ, Woods JE, et al.: Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999, 240:77–84.CrossRefGoogle Scholar
  40. 40.
    Hartmann LC, Sellers TA, Schaid DJ, et al.: Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst 2001, 93:1633–1637.PubMedCrossRefGoogle Scholar
  41. 41.
    Rebbeck TR, Friebel T, Lynch HT, et al.: Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2004, 22:981–983.CrossRefGoogle Scholar
  42. 42.
    Walsh T, Casadei S, Hale Coats K, et al.: Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 2006, 10:2981–2921.Google Scholar
  43. 43.
    Genetic testing for hereditary cancer syndromes resource guide. Myriad Genetic Laboratories, Inc. website. Accessed October 16, 2007.
  44. 44.
    Pierce LJ, Strawderman M, Narod SA, et al.: Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J Clin Oncol 2000, 18;3360–3369.PubMedGoogle Scholar
  45. 45.
    Pierce LJ, Levin AM, Rebbeck TR, et al.: Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol 2006, 24:2437–2443.PubMedCrossRefGoogle Scholar
  46. 46.
    Schwartz MD, Lerman C, Brogan B, et al.: Impact of BRCA1/BRCA2 counseling and testing on newly diagnosed breast cancer patients. J Clin Oncol 2004, 22:1823–1829.PubMedCrossRefGoogle Scholar
  47. 47.
    Lakhani SR, Van De Vijver MJ, Jacquemier J, et al.: The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol 2002, 20:2310–2318.PubMedCrossRefGoogle Scholar
  48. 48.
    Rennert G, Bisland-Naggan S, Barnett-Griness O, et al.: Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 2007, 357:115–123.PubMedCrossRefGoogle Scholar
  49. 49.
    Cass I, Baldwin RL, Varkey T, et al.: Improved survival in women with BRCA-associated ovarian carcinoma. Cancer 2003, 97:2187–2195.PubMedCrossRefGoogle Scholar
  50. 50.
    Venkitaraman AR: Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 2002, 108:171–182.PubMedCrossRefGoogle Scholar
  51. 51.
    Kennedy RD, Quinn JE, Mullan PB, et al.: The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst 2004, 96:1659–1668.PubMedGoogle Scholar
  52. 52.
    Yap TA, Boss DS, Fong PC, et al.: Phase I study of AZD2281 (KU-0059436), a poly ADP-ribose polymerase (PARP) inhibitor in cancer patients, including BRCA1/2 mutation carriers. J Clin Oncol 2007, 25:145S.Google Scholar

Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  1. 1.Cancer Risk Evaluation ProgramUniversity of Pennsylvania, Abramson Cancer CenterPhiladelphiaUSA

Personalised recommendations