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Home > Understanding Breast Cancer > Breast Cancer Research > Table 11: BRCA1 and BRCA2 gene mutations and cancer risk

  


Table 11: BRCA1 and BRCA2 gene mutations and cancer risk

 

This summary table contains detailed information about research studies. Summary tables offer an informative look at the science behind many breast cancer guidelines and recommendations. However, they should be viewed with some caution. In order to read and interpret research tables successfully, it is important to understand some key concepts. Learn how to read a research table.

BRCA1 and BRCA2 mutations are rare in the general population. In the U.S., between one in 400 and one in 800 women in the general population carry a BRCA mutation [1]. However, women of Ashkenazi Jewish descent are more likely to have a BRCA mutation (about one in 40 women) [1].

Risk of breast and ovarian cancer

Women who have a BRCA1 or BRCA2 gene mutation have an increased risk of both breast and ovarian cancer, but estimates of this risk vary greatly. BRCA carriers have 40 to 70 percent chance of getting breast cancer by age 70 and a 10 to 70 percent chance of getting ovarian cancer by age 70. In comparison, the average woman in the U.S. has an eight percent chance of getting breast cancer and a 1½ percent chance of getting ovarian cancer by age 70 [1-2].

Men who have a BRCA2 gene mutation also have an increased risk of breast cancer [1].

Risk of other types of cancer

People who have a BRCA1 or BRCA2 gene mutation may also have an increased risk of colon cancer, prostate cancer (in men) and some second primary cancers (new cancers that develop after a first breast cancer). However, data on these risks are limited.

International Breast Cancer Linkage Consortium

Much of the research on genetic mutations and breast cancer risk has been done by the International Breast Cancer Linkage Consortium. This group has collected data on over 200 families worldwide. Each family has at least four family members with breast cancer.

Study selection criteria: For family-based studies: Studies with more than 200 families that have four or more members with breast cancer. For population-based studies: Studies with at least 100 cancer cases. For pooled analyses: Studies with at least 400 families.  

Table note: BRCA1 carriers seem to have slightly different cancer risks than BRCA2 carriers. However, the two groups are sometimes combined in studies since there are so few data on either group alone.    

Study 

Study Characteristics 

Study Population
(number of participants)
 

Cumulative Risk of Different Types of Cancer
by age 70 (95% CI)
 

 

 Second Cancers in Women with Breast Cancer 

Breast Cancer 

Ovarian
Cancer
 

Other
Cancers
 

Breast Cancer (other side) 

Ovarian Cancer 

Family-based studies 

BRCA1 

German Consortium for Hereditary Breast and Ovarian Cancer [3] 

BRCA1 mutation carrier families

1,743 families

     

44%
 (38-51%)*,† 

 

Breast Cancer Linkage Consortium [4-6]

BRCA1 mutation carrier families

237 families that have 4 or more members with breast cancer

 87%
(72-95%)

63% 

Colon cancer:
Highly increased risk

64%

44%
(28-56%) 

Evans et al. [7]

BRCA1 mutation carrier families

223 families

 68%
(65-71%)

60%

     

BRCA2 

German Consortium for Hereditary Breast and Ovarian Cancer [3] 

BRCA2 mutation carrier families

818 families

     

34%
(22-45%)*,†  

 

Breast Cancer Linkage Consortium [8-10]

BRCA2 mutation carrier families

 237 families that have 4 or more members with breast cancer

 84%
(43-95%)

 27%
(0-47%)

Prostate cancer (men):
Highly increased risk

 52%
(42-61%)

 

Population-based studies 

Struewing et al. [11]

Jewish residents of Washington, DC area

5,318

56%
(40-73%) 

 16%
(6-28%)

Prostate cancer (men):
16%
(4-30%)
   

EMBRACE [12]

Women with a BRCA1 or BRCA2 mutation

1,887
(651 breast cancer cases)

60%
(44-75%)
(BRCA1)


55%
(41-70%)
(BRCA2)

59%
(43-76%)
(BRCA1)


17%
(8-34%) 
(BRCA2

   83%
(69-94%)
(BRCA1)


62%
(44-80%) 
(BRCA2)

 

Lubinski et al. [13]

 Women with a BRCA1 mutation

 1,477
(130 breast cancer cases)

 Women in North America:
76%

Women in Poland:
58% 

       

Begg et al. [14]

 Women with breast cancer diagnosed before age 55

1,394

36%
(21-58%)
(BRCA1

 47%
(25-100%)
(BRCA2)§ 

   

48%
(30-67%)
(BRCA1

 59%
(30-84%)
(BRCA2)|| 

 

King et al. [15]

Ashkenazi Jewish women with breast cancer

1,008

69%
(BRCA1

 74%
(BRCA2)

 46%
(BRCA1

 12%
(BRCA2)

     

Niell et al. [16]

Ashkenazi Jews

1,002 colon cancer cases

   

Colon cancer:
No excess risk

   

Leongamornlert et al. [17]

British men with prostate cancer 

 913

    Prostate cancer:
9%
(BRCA1
   

Tryggvadottir et al. [18]

Icelandic women with breast cancer and their first-degree relatives 

847 women with breast cancer and 2,836 first degree relatives

46%
(BRCA2)

       

Thorlacius et al. [19]

Icelandic women with breast cancer

575

37%
(22-54%)
(BRCA2

       

Warner et al. [20]

Jewish women with breast cancer

457

60% (BRCA1)

28% (BRCA2)

       

Rafner et al. [21]

Icelandic women with ovarian cancer

235

 

Highly increased risk  (BRCA2)

     

Kirchhoff et al. [22]

Ashkenazi Jewish men with prostate cancer

251

   

Prostate cancer (men): Increased risk  (BRCA2)

No excess risk (BRCA1)

   

Pooled analyses 

Antoniou et al. [23]

22 studies

429 families

46-59% (BRCA1)

39-51% (BRCA2)

33-36%
(BRCA1)

11-12%
(BRCA2)

Prostate cancer (men): Increased risk

Pancreatic cancer: Increased risk

   

 

* Cumulative risk 25 years after the first breast cancer.

† For women who had their first breast cancer at age 40 or younger, the risk of contralateral (opposite side) breast cancer was higher. Twenty-five years after their first breast cancer, 55% of women with a BRCA1 mutation diagnosed at age 40 or younger developed a contralateral breast cancer compared to 22% of women first diagnosed after age 50. For women with a BRCA2 mutation diagnosed at age 40 or younger, 38% developed a contralateral breast cancer compared to 16% of women diagnosed after age 50. 

‡ For women who did not have an oophorectomy (surgical removal of the ovaries) to lower their cancer risk.

§ By age 80, cumulative risk of breast cancer increased to 58% (30-80%) for BRCA1 carriers and 58% (38-81%) for BRCA2 carriers.

|| By age 80, cumulative risk of a second breast cancer in the opposite breast increased to 47% (25-100%) for BRCA1 carriers and 60% (34-92%) for BRCA2 carriers.

¶ Cumulative risk up to age 65.

 

References  

  1. National Cancer Institute. High-penetrance breast and/or ovarian cancer susceptibility genes. http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional/page2#Section_95, 2013.
  2. American Cancer Society. Do we know what causes ovarian cancer? http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-what-causes, 2013.
  3. Rhiem K, Engel C, Graeser M, et al. The risk of contralateral breast cancer in patients from BRCA1/2 negative high risk families as compared to patients from BRCA1 or BRCA2 positive families: a retrospective cohort study. Breast Cancer Res. 14(6):R156, 2012.
  4. Easton DF, Bishop DT, Ford D, Crockford GP. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 52(4):678-701, 1993.
  5. Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet. 56(1):265-271, 1995.
  6. Ford D, Easton DF, Bishop DT, et al. Breast Cancer Linkage Consortium: Risks of cancer in BRCA1-mutation carriers. Lancet. 343(8899):692-695, 1994.
  7. Evans DG, Shenton A, Woodward E, Lalloo F, Howell A, Maher ER. Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family. BMC Cancer. 8:155, 2008.
  8. Ford D, Easton DF, Stratton M, et al. Genetic heterogeneity and penetrance analysis of the BRCA 1 and BRCA 2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 62(3):676-89, 1998.
  9. Easton DF, Steele L, Fields P, et al. Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12-13. Am J Hum Genet. 61(1):120-128, 1997.
  10. Cancer risks in BRCA2 mutation carriers. The breast cancer linkage consortium. J Natl Cancer Inst. 91(15):1310-1316, 1999.
  11. Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Jewish Ashkenazi Jews. N Engl J Med. 336(20):1401-1408, 1997.
  12. Mavaddat N, Peock S, Frost D, et al. on behalf of EMBRACE. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst. 105(11):812-822, 2013.
  13. Lubinski J, Huzarski T, Byrski T, et al. for the Hereditary Breast Cancer Clinical Study Group. The risk of breast cancer in women with a BRCA1 mutation from North America and Poland. Int J Cancer. 131(1):229-34, 2012.
  14. Begg CB, Haile RW, Borg A, et al. Variation of breast cancer risk among BRCA1/2 carriers. JAMA. 299(2):194-201, 2008.
  15. King MC, Marks JH, and Mandell JB. Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2. Science. 302(5645):643-6, 2003.
  16. Niell BL, Rennert G, Bonner JD, et al. BRCA1 and BRCA2 Founder Mutations and the Risk of Colorectal Cancer. J Natl Cancer Inst. 96(1):15-21, 2004.
  17. Leongamornlert D, Mahmud N, Tymrakiewicz M, et al. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer. 106(10):1697-701, 2012.
  18. Tryggvadottir L, Sigvaldason H, Olafsdottir GH, et al. Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000. J Natl Cancer Inst. 98(2):116-22, 2006.
  19. Thorlacius S, Struewing JP, Hartge P, et al. Population-based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet. 352(9137):1337-9, 1998.
  20. Warner E, Foulkes W, Goodwin P, et al. Prevalence and Penetrance of BRCA1 and BRCA2 Gene Mutations in unselected Ashkenazi Jewish Women with Breast Cancer. J Natl Cancer Inst. 91(14):1241-1247, 1999.
  21. Rafner T, Benediksdottir KR, Eldon BJ, et al. BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study. Eur J Cancer. 40(18):2788-93, 2004.
  22. Kirchhoff T, Kauff ND, Mitra N, et al. BRCA mutation and risk of prostate cancer in Ashkenazi Jews. Clin Cancer Res. 10(9):2918-21, 2004.
  23. Antoniou AC, Cunningham AP, Peto J, et al. The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer. 98(8):1457-66, 2008.

Updated 08/28/13