Abstract
Multiple studies have shown that risk-reducing salpingo-oophorectomy (RRSO) not only reduces the risk of gynecologic cancer (ovarian, fallopian tube, and primary peritoneal) cancer in women with mutations in either BRCA1 or BRCA2, but that if performed premenopausally, RRSO also reduces the risk of breast cancer. It has, however, become apparent that mutations in BRCA1 and BRCA2 cause related, but distinct, cancer susceptibility syndromes. For example, BRCA1-associated breast cancer is markedly more likely to be estrogen receptor negative than BRCA2-associated breast cancer. Similarly, the ovarian cancer penetrance is substantially lower for carriers of BRCA2 mutations than for carriers of BRCA1 mutations. These differences raise the question as to whether RRSO may have different impacts on cancer risk depending on the specific gene mutated. This article reviews what is known about RRSO for reducing BRCA-associated breast and gynecologic cancer risk, as well as early data suggesting RRSO may have differential effects depending upon whether BRCA1 or BRCA2 is mutated.
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References and Recommended Reading
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, 336:1401–1408.
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, 62:676–689.
Antoniou A, Pharoah PD, Narod S, et al.: Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 2003, 72:1117–1130.
King MC, Marks JH, Mandell JB, et al.: Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003, 302:643–646.
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.
Foulkes WD, Metcalfe K, Sun P, et al.: Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: The influence of age, grade, and histological type. Clin Cancer Res 2004, 10:2029–2034.
Kauff ND, Satagopan JM, Robson ME, et al.: Risk-reducing salpingo-oophorectomy in women with at BRCA1 or BRCA2 mutation. N Engl J Med 2002, 346:1609–1615.
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.
Nunn TW: On Cancer of the Breast. London: J & A Churchill; 1882:71.
Love RR, Philips J: Oophorectomy for breast cancer: history revisited. J Natl Cancer Inst 2002, 94:1433–1434.
Liber AM: Ovarian cancer in a mother and five daughters. Arch Pathol 1950, 49:280–290.
Feinleib M: Breast cancer and artificial menopause: A cohort Study. J Natl Cancer Inst 1968, 41:315–329.
Brinton LA, Schairer C, Hoover RN, et al.: Menstrual factors and risk for breast cancer. Cancer Invest 1988, 6:245–254.
Tobacman JK, Greene MH, Tucker MS, et al.: Intraabdominal carcinomatosis after prophylactic oophorectomy in ovarian-cancer prone families. Lancet 1982, 2:795–797.
Piver MS, Jishi MF, Tsukada Y, et al.: Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer: A report of the Gilda Radner Familial Ovarian Cancer Registry. Cancer 1993, 71:2751–2755.
Strewing JP, Watson P, Easton DF, et al.: Prophylactic oophorectomy in inherited breast/ovarian cancer families. J Natl Cancer Inst Monogra 1995, 17:33–35.
Miki y, Swensen J, Shattuck-Eidends D, et al.: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994, 266:66–71.
Wooster R, Bignell G, Lancaster J, et al.: Identification of the breast cancer susceptibility gene BRCA2. Nature 1995, 378:789–792.
Burke W, Daly M, Garber J, et al.: Recommendations for follow-up care individuals with an inherited predisposition to cancer: II; BRCA1 and BRCA2—Cancer Genetics Studies Consortium. JAMA 1997, 277:997–1003.
Kauff ND, Barakat RR: Risk reducing salpingo-oophorectomy in patients with germline mutations in BRCA1 or BRCA2. J Clin Oncol 2007, 25:2921–2927.
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.
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.
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.
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.
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, 26:1331–1337.
Anglian Breast Cancer Study Group: Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer 2000, 83:1301–1308.
Satagopan JM, Boyd J, Kauff ND, et al.: Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Clin Cancer Res 2002, 8:3776–3781.
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.
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.
Metcalfe K, Lynch HT, Ghadirian P, et al.: Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 2004, 22:2328–2335.
Klaren HM, van’t Veer LJ, van Leeuwen FE, et al.: Potential for bias in studies on efficacy of prophylactic surgery for BRCA1 and BRCA2 mutation. J Natl Cancer Inst 2003, 95:941–947.
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, 101:80–87.
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.
Hartmann LC, Degnim A, Schaid DJ: Prophylactic mastectomy for BRCA1/2 carriers: progress and more questions. J Clin Oncol 2004, 22:981–983.
Cuzick J, Powles T, Veronesi U, et al.: Overview of the main outcomes in breast-cancer prevention trials. Lancet 2003, 361:296–300.
Chlebowski RT, Col N, Winer EP, et al.: American Society of Clinical Oncology technology assessment of pharmacologic interventions for breast cancer risk reduction including tamoxifen, raloxifene, and aromatase inhibition. J Clin Oncol 2002, 20:3328–3343.
Cuzick J: Aromatase inhibitors for breast cancer prevention. J Clin Oncol 2005, 23:1636–1643.
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Arnold, A.G., Kauff, N.D. Prophylactic oophorectomy may differentially reduce breast cancer risk in women with BRCA1 versus BRCA2 mutations. Curr Breast Cancer Rep 1, 157–161 (2009). https://doi.org/10.1007/s12609-009-0022-4
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DOI: https://doi.org/10.1007/s12609-009-0022-4