The Who, What, Where, When and Sometimes, Why.

BRCA1 and BRCA2 gene mutations and cancer risk

This summary table contains detailed information about research studies. Summary tables are a useful way to look at the science behind many breast cancer guidelines and recommendations. However, to get the most out of the tables, it’s important to understand some key concepts. Learn how to read a research table.

Introduction: In the U.S., about 1 in 400 people in the general population have a BRCA1 or BRCA2 gene mutation [1]. People of Ashkenazi Jewish descent are more likely to have a BRCA1/2 mutation (about 1 in 40) [1].

Risk of breast and ovarian cancer

Women who have a BRCA1/2 gene mutation have an increased risk of both breast and ovarian cancer. Estimates of these risks vary greatly.

By age 70, women who have a BRCA1/2 gene mutation have 45-65 percent chance of getting breast cancer and a 10-70 percent chance of getting ovarian cancer [1-2].

In comparison, the average woman in the U.S. has an 8 percent chance of getting breast cancer and a less than 2 percent chance of getting ovarian cancer by age 70 [1-2].

Men who have a BRCA2 gene mutation (and possibly those who have a BRCA1 mutation) also have an increased risk of breast cancer [1].

Risk of other types of cancer

People who have a BRCA1/2 gene mutation also have an increased risk of pancreatic cancer, prostate cancer (in men) and some second primary cancers (new cancers that develop after breast cancer).

Learn more about BRCA1, BRCA2 and other gene mutations.

International Breast Cancer Linkage Consortium

Much of the research on inherited gene 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 4 family members with breast cancer.

Study selection criteria: For family-based studies: Studies with more than 150 families. For population-based studies: Studies with at least 500 cancer cases. For pooled analyses: Studies with at least 400 families.

Table note: People who have a BRCA1/2 gene mutation may be called BRCA1/2 carriers. 

BRCA1 carriers have slightly different cancer risks than BRCA2 carriers. However, the 2 groups are sometimes combined in studies since there may be few data on either group alone.

Study

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] 

1,154
BRCA1 mutation carrier families

   

44%
 (38-51%)*,† 

 

Brohet et al. [4]

582
BRCA1 mutation carrier families with an average of 4 family members with breast cancer

45%
(36-52%)

31%
(17-43%)

   

Breast Cancer Linkage Consortium [5-7]

237
BRCA1 mutation carrier 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. [8]

223
BRCA1 mutation carrier families

 68%
(65-71%)

60%

   

Nielsen et al. [9]

181
BRCA1 mutation carrier families

35%

29%

   

BRCA2

German Consortium for Hereditary Breast and Ovarian Cancer [3]

575 
BRCA2 mutation carrier families

   

34%
(22-45%)*,† 

 

Breast Cancer Linkage Consortium [10-12]

237
BRCA2 mutation carrier families with 4 or more members with breast cancer

84%
(43-95%)

27%
(0-47%)

Prostate cancer (men):
Highly increased risk

52%
(42-61%)

 

Brohet et al. [4]

176
BRCA2 mutation carrier families with an average of 4 family members with breast cancer 

27%
(14-38%)

6%
(2-11%)

   

Nielsen et al. [9]

 118
BRCA2 mutation carrier families

44%

15%

   

Population-based studies

van den Broek et al. [13]

6,294
Dutch women with breast cancer diagnosed before age 55

   

 21%
(15-27%)
(BRCA1)‡

11%
(5-20%)
(BRCA2)‡

 

EMBRACE [14]

1,887
Women with a BRCA1/2 mutation
(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)

 

Begg et al. [15]

 1,394
Women with breast cancer diagnosed before age 55

36%
(21-58%)
(BRCA1

 47%
(25-100%)
(BRCA2

  

48%
(30-67%)
(BRCA1)|| 

 59%
(30-84%)
(BRCA2)|| 

 

King et al. [16]

1,008
Ashkenazi Jewish women with breast cancer

69%
(BRCA1

 74%
(BRCA2)

 46%
(BRCA1

 12%
(BRCA2)

   

Niell et al. [17]

1,002
Ashkenazi Jewish people with colon cancer

  

Colon cancer:
No excess risk

  

Leongamornlert et al. [18]

913
British men with prostate cancer

  

Prostate cancer:
9%
(BRCA1

  

Tryggvadottir et al. [19]

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

46%
(BRCA2)

    

Thorlacius et al. [20]

575
Icelandic women with breast cancer

37%
(22-54%)
(BRCA2

    

Pooled analyses

International BRCA1/2 Carrier Cohort Study [21] 

3,886
women with a BRCA1/2 mutation
(426 cases) 

72%
(65-79%)
(BRCA1)**

69%
(61-77%)
(BRCA2)**

 

 

  

 

5,066
women with a BRCA1/2 mutation
(109 cases) 

 

44%
(36-53%)
(BRCA1)**

17%
(11-25%)
(BRCA2)**

 

  

 

2,213
women with a BRCA1/2 mutation diagnosed with breast cancer
(245 cases) 

 

 

 

 40%
(35-45%)
(BRCA1)**,††

26%
(20-33%)
(BRCA2)**,††

 

Antoniou et al. [22]

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

  

 

* Results are for 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.

‡ Results are for cumulative risk 10 years after the first breast cancer.

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

|| By age 80, cumulative risk of a contralateral (opposite side) breast cancer was 47% (25-100%) for BRCA1 carriers and 60% (34-92%) for BRCA2 carriers.

¶ Results are for cumulative risk up to age 65.

** Results are for cumulative risk up to age 80.

†† Results are for cumulative risk 20 years after the first breast cancer.

References

  1. National Cancer Institute. Genetics of breast and gynecologic cancers (PDQ®)–Health professional version. High-penetrance breast and/or gynecologic cancer susceptibility genes. https://www.cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq#_88, 2019.
  2. American Cancer Society. Ovarian cancer risk factors. https://www.cancer.org/cancer/ovarian-cancer/causes-risks-prevention/risk-factors.html, 2018.
  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. Brohet RM, Velthuizen ME, Hogervorst FB, et al. Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations. J Med Genet. 51(2):98-107, 2014.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Nielsen HR, Nilbert M, Petersen J, et al. BRCA1/BRCA2 founder mutations and cancer risks: impact in the western Danish population. Fam Cancer. 15(4):507-12, 2016.
  10. 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.
  11. 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.
  12. The Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst. 91(15):1310-1316, 1999.
  13. van den Broek AJ, van ‘t Veer LJ, Hooning MJ, et al. Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers. J Clin Oncol. 34(5):409-18, 2016.
  14. 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.
  15. Begg CB, Haile RW, Borg A, et al. Variation of breast cancer risk among BRCA1/2 carriers. JAMA. 299(2):194-201, 2008.
  16. 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.
  17. 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.
  18. Leongamornlert D, Mahmud N, Tymrakiewicz M, et al. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer. 106(10):1697-701, 2012.
  19. 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.
  20. 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.
  21. Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 317(23):2402-2416, 2017.
  22. 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. 

 

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