Women's College Research Institute

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Findings: Familial Breast Cancer Research Unit

Pregnancy:
Carriers of the BRCA1 and BRCA2 gene mutations who have children are significantly more likely to develop breast cancer by age 40 than carriers who have not had any children. Each pregnancy is associated with an increased cancer risk. An early first pregnancy does not mean protection for carriers of BRCA1 or BRCA2 mutations.1

Breastfeeding:
Women who have a BRCA1 mutation and breast-fed for a cumulative total of more than one year had a statistically significant reduced risk of breast cancer.2

Oral Contraceptives:
Oral-contraceptive use may reduce the risk of ovarian cancer in women with mutations in the BRCA1 or BRCA2 gene.3

Among BRCA1 mutation carriers, women who first used oral contraceptives before 1975, who used them before age 30, or who used them for five or more years may have an increased risk of early-onset breast cancer. Oral contraceptives do not appear to be associated with risk of breast cancer in BRCA2 carriers, but data for BRCA2 carriers is limited.4

Fertility Drugs:
The use of fertility medications does not adversely affect the risk of breast cancer among BRCA mutation carriers. However, the impact of fertility drug use among BRCA mutation carriers has not been studied closely due to the small number of carriers who have used fertility drugs. Any findings should be interpreted with caution. Further studies are required in this field. 5

Tubal Ligation:
Tubal ligation is a suitable option to reduce the risk of ovarian cancer in women with BRCA1 mutations who have completed childbearing.6

Oophorectomy:
The high incidence of ovarian cancer suggests that oophorectomy (surgical removal of the ovaries) should be recommended in female BRCA1 and BRCA2 mutation carriers with a diagnosis of breast cancer, especially those with stage I disease. Breast cancer systemic therapy did not significantly alter the risk of ovarian cancer.7

Oophorectomy is an effective means of reducing the risk of breast cancer in carriers of BRCA1 mutations. The data suggests oophorectomy is protective in BRCA2 carriers as well, but this needs to be confirmed in other studies.8

Oophorectomy is associated with a reduced risk of ovarian and fallopian tube cancer in high-risk women, although there is a substantial residual risk for peritoneal cancer in BRCA1 and BRCA2 mutation carriers following prophylactic salpingo-oophorectomy (a type of preventive surgery performed by removing the fallopian tubes and ovaries).9

Tamoxifen:
Tamoxifen, a drug used in the treatment of breast cancer, has been shown to reduce the risk of contralateral (affecting both breasts) breast cancer in women with mutations in the BRCA1 or BRCA2 gene. The protective effect of tamoxifen seems independent of that of removal of the ovaries.10

The protective effect of tamoxifen was not seen among women who had their ovaries removed but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause.11

The risk of contralateral breast cancer in women with a BRCA mutation is approximately 40 per cent at 10 years after the first breast cancer diagnosis, and is reduced in women who take tamoxifen or who undergo an ovary-removal surgery.12

Screening and Preventive Practices:
We found no association between ever having screening mammography and risk of breast cancer. Prospective studies are needed to confirm the results.13

Other:
Early chest X-rays may be a risk factor for breast cancer in BRCA1 carriers.14

Prostate Cancer:
Men with BRCA2 mutations have been found to be at increased risk of developing prostate cancer. It may be important to develop targeted chemotherapies to treat prostate cancer in men with a BRCA2 mutation.15

Relevant Publications

1. Jernström H, Lerman C, Ghadirian P, Lynch H, Weber B, Garber J, Daly M, Olopade O, Foulkes WE, Warner E, Brunet J-S and Narod SA. Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2. Lancet, 354:1846-50, 1999.

2. Jernström H, Lubinski L, Lynch HT, Ghadirian P, Neuhausen S, Isaacs C, Weber B, Horsman D, Rosen B, Foulkes WD, Friedman E, Gershoni-Baruch R, Ainsworth P, Daly M, Garber J, Olsson H, Sun P, Narod SA. Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst, 96:1094-8, 2004.

3. Narod SA, Risch H, Moslehi R, Neuhausen S, Moller P, Olsson H, Provencher D, Radice P, Evans G, Bishop S, Brunet J-S and Ponder B. Oral contraceptives and the risk of hereditary ovarian cancer. N Engl J Med, 339:424-8, 1998.

4. Narod SA, Dubé M-P, Klijn J, Lubinski J, Lynch HT, Ghadirian P, Provencher D, Heimdal K, Moller P, Isaacs C, Weber B, Friedman E, Gershoni-Baruch R, Rennert G, Pasini B, Wagner T, Daly M, Garber JE, Neuhausen S, Robson M, Offit K, Ainsworth P, Olsson H, Evans G, Osborne M, Couch F, Foulkes W, Warners E, Kim-Sing C, Olopade O, Tung N, Saal HM, Weitzel J, Merajver S, Gauthier-Villars M, Jernstrom H, Sun P, Brunet J-S. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 carriers. J Natl Can Inst, 94:1773-9, 2002.

5. Pal T, Vadaparampil S, Betts J, Miree C, Li S, Narod SA. BRCA1/2 in high-risk African American women with breast cancer: providing genetic testing through various recruitment strategies. Genet Test, 12:401-7, 2008.

6. Narod SA, Sun P, Ghadirian P, Lynch H, Isaacs C, Garber J, Weber B, Karlan B, Fishman D, Rosen B, Tung N, Neuhausen SL and the Hereditary Ovarian Cancer Clinical Study Group. Tubal ligation and the risk of ovarian cancer in carriers of BRCA1 or BRCA2 mutations: A case-control study. Lancet, 357:1467-70, 2001.

7. Metcalfe K, Lynch H, Ghadirian P, Tung N, Olivotto I, Foulkes W, Warner E, Olopade O, Eisen A, Weber B, McLennan J, Sun P, Narod SA. The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers. Gynecol Oncol, 96:222-6, 2005.

8. Eisen A, Lubinski J, Klijn J, Moller P, Lynch H, Offit K, Weber B, Rebbeck T, Neuhausen S, Ghadirian P, Foulkes W, Gershoni-Baruch R, Friedman E, Rennert G, Isaacs C, Kim-Sing C, Ainsworth P, Couch F, Garber J, Daly M, Rosen B, Olopade O, Karlan B, Tung N, Saal H, Weitzel J, Eng C, Sun P, Narod SA. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: An international case-control study. J Clin Oncol, 23: 7491-6, 2005.

9. Finch A, Beiner M, Lubinksi J, Lynch HT, Moller P, Rosen B, Murphy J, Ghadirian P, Friedman E, Foulkes WD, Kim-Sing C, Wagner T, Tung N, Couch F, Stoppa-Lyonnet D, Ainsworth P, Daly M, Pasini B, Gershoni-Baruch R, Eng C, Olopade OI, Mclennan J, Karlan B, Sun P, Narod SA. Salpingo-oophorectomy and the risk of ovarian, fallopian and peritoneal cancers in women with BRCA1 or BRCA2 mutations. JAMA, 96:185-92, 2006.

10. Narod SA, Brunet J-S, Ghadirian P, Robson M, Heimdahl K, Neuhausen S, Stoppa-Lyonnet D, Lerman C, Radice P, de los Rios P, Weber B, Lynch H for the Hereditary Breast Cancer Clinical Study Group. Tamoxifen and the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers: a case-control study. Lancet, 356:1876-81, 2000.

11. Gronwald J, Tung N, Foulkes WD, Offit K, Gershoni R, Daly M, Kim-Sing C, Olsson H, Ainsworth P, Eisen A, Saal H, Friedman E, Olopade O, Osborne M, Weitzel J, Lynch HT, Ghadirian P, Lubinski J, Sun P, Narod SA and the Hereditary Breast Cancer Clinical Study Group. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: An update. Int J Cancer, 118:2281-4, 2006.

12. Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, Olopade OI, Eisen A, Weber B, McLennan J, Sun P, Foulkes WD, Narod SA. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol, 22:2328-35, 2004.

13. Narod SA, Lubinksi J, Ghadirian P, Lynch HT, Moller P, Foulkes WD, Rosen B, Kim-Sing C, Isaacs C, Domchek S, Sun P, and the Hereditary Breast Cancer Clinical Study Group. Screening mammography and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Lancet Oncol, 5:402-406, 2006.

14. Gronwald J, Pijpe A, Byrski T, Huzarski T, Stawicka M, Cybulski C, Leeuwen F, Lubinski J, Narod SA. Early radiation exposures and BRCA1-associated breast cancer in young women from Poland. Breast Cancer Res Treat. 112:581-4, 2008.

15. Narod SA, Neuhausen S, Vichodez G, Armel S, Lynch HT, Ghadirian P, Cummings S, Olopade O, Couch F, Wagner T, Warner E, Foulkes WD, Saal H, Weitzel J, Tulman A, Poll AS, Nam R, Sun P and the Hereditary Breast Cancer Study Group. Rapid progression of prostate cancer in men with a BRCA2 mutation. Br J Cancer, 99:371-4, 2008.

 

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