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

Research table: BRCA1 and BRCA2 inherited 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 to 1 in 800 people in the general population have a BRCA1 or BRCA2 (BRCA1/2) inherited gene mutation [1]. People of Ashkenazi Jewish descent are more likely to have a BRCA1/2 inherited gene mutation (about 1 in 40) [1].

People who have a BRCA1/2 inherited gene mutation may be called BRCA1/2 carriers.

Risk of breast cancer and ovarian cancer

Women who have a BRCA1 or BRCA2 (BRCA1/2) inherited gene mutation have an increased risk of breast cancer and ovarian cancer. Estimates of these risks vary greatly.

Women who have a BRCA1/2 inherited gene mutation have more than a 60% chance of getting breast cancer in their lifetimes and a 10%-60% chance of getting ovarian cancer [2].

In comparison, the average woman in the U.S. has an 8% chance of getting breast cancer and a less than 2% chance of getting ovarian cancer by age 70 [3-4].

Men who have a BRCA2 inherited gene mutation, and to a lesser degree men who have a BRCA1 inherited gene mutation, also have an increased risk of breast cancer [1].

Risk of other types of cancer

People who have a BRCA1 or BRCA2 (BRCA1/2) inherited gene mutation also have an increased risk of pancreatic cancer, prostate cancer (in men) and melanoma (BRCA2 gene mutations only). They also have an increased risk of some second primary cancers (new cancers that develop after breast cancer).

Learn more about BRCA1/2 inherited gene mutations in women.

Learn more about BRCA1/2 inherited gene mutations in men.

Learn about other inherited gene mutations related to breast cancer.

International Breast Cancer Linkage Consortium

The International Breast Cancer Linkage Consortium has done much of the research on inherited gene mutations and breast cancer risk. 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: BRCA1 carriers have slightly different cancer risks than BRCA2 carriers. However, they are sometimes combined in studies since there may be few data on either group alone.

Study

Study Population
(number of participants)

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

Consortium of Investigators of Modifiers of BRCA1/2 [5]

3,184 BRCA1 mutation carrier families

Male breast cancer:
Less than 1%
(0.1%-2%)

 

Pancreatic cancer (women):
2%
(1%-4%)

Pancreatic cancer (men):
3%
(2%-5%)

   

German Consortium for Hereditary Breast and Ovarian Cancer [6]

1,626
BRCA1 mutation carrier families

62%
(53%-71%)*

   

25%
(20%-32%)†

 

Brohet et al. [7]

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

45%
(36%-52%)

31%
(17%-43%)

     

Ho et al. [8]

271
BRCA1 mutation carrier families from Malaysia and Singapore

Chinese family ancestry:
55%
(51%-60%)**

Indian family ancestry:
49%
(44%-53%)**

Malay family ancestry:
40%
(36%-44%)**

31%
(27%-36%)**

     

Breast Cancer Linkage Consortium [9-11]

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. [12]

223
BRCA1 mutation carrier families

68%
(65%-71%)

60%

     

Nielsen et al. [13]

181
BRCA1 mutation carrier families

35%

29%

    

BRCA2

Consortium of Investigators of Modifiers of BRCA1/2 [5]

2,157 BRCA2 mutation carrier families

Male breast cancer:
4%
(2%-8%)

 

Pancreatic cancer (women):
2%
(1%-4%)

Pancreatic cancer (men):
3%
(2%-5%)

Prostate cancer (men):
27%
(21%-35%)

   

German Consortium for Hereditary Breast and Ovarian Cancer [6]

983
BRCA2 mutation carrier families

43%
(32%-56%)*

   

7%
(3%-13%)†

 

Ho et al. [8]

301
BRCA2 mutation carrier families from Malaysia and Singapore

Chinese family ancestry:
42%
(38%-45%)**

Indian family ancestry:
36%
(33%-40%)**

Malay family ancestry:
29%
(26%-32%)**

12%
(10%-15%)**

     

Breast Cancer Linkage Consortium [14-16]

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. [7]

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

27%
(14%-38%)

6%
(2%-11%)

     

Nielsen et al. [13]

118
BRCA2 mutation carrier families

44%

15%

     

Population-based studies

CARRIERS study [17]

15,104
Women with breast cancer
(801 cases)

     

23%
(16%-33%)‡
(BRCA1)

17%
(12%-24%)‡
(BRCA2)

 

van den Broek et al. [18]

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

     

21%
(15%-27%)‡
(BRCA1)

11%
(5%-20%)‡
(BRCA2)

 

EMBRACE [19]

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. [20]

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. [21]

1,008
Ashkenazi Jewish women with breast cancer

69%
(BRCA1

74%
(BRCA2)

46%
(BRCA1

12%
(BRCA2)

    

Niell et al. [22]

1,002
Ashkenazi Jewish people with colon cancer

   

Colon cancer:
No excess risk

   

Leongamornlert et al. [23]

913
British men with prostate cancer

   

Prostate cancer:
9%¶
(BRCA1)

   

Tryggvadottir et al. [24]

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

46%
(BRCA2)

       

Thorlacius et al. [25]

575
Icelandic women with breast cancer

37%
(22%-54%)
(BRCA2)

     

Pooled analyses

International BRCA1/2 Carrier Cohort Study [26]

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. [27]

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 risk up to age 60.

† Results are for risk up to 10 years after the first breast cancer. Risk up to 20-25 years after the first breast cancer was 42% (33%-53%) for BRCA1 carriers and 25% (12%-46%) for BRCA2 carriers.

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

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

|| By age 80, 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 risk up to age 65.

** Results are for risk up to age 80.

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

References

  1. National Cancer Institute. BRCA1 and BRCA2: Cancer risks and management (PDQ®)–Health professional version. https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-genes-hp-pdq, 2024.
  2. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: Genetic/familial high-risk assessment—breast, ovarian and pancreatic cancer. Version 3.2024. http://www.nccn.org, 2024.
  3. Surveillance Research Program, National Cancer Institute. SEER*Explorer. Breast cancer risk from birth over time, 2017-2019, by sex, all races, risk of being diagnosed with cancer. Accessed on November 14, 2023. https://seer.cancer.gov/explorer/, 2023.
  4. American Cancer Society. Ovarian cancer risk factors. https://www.cancer.org/cancer/ovarian-cancer/causes-risks-prevention/risk-factors.html, 2021.
  5. Li S, Silvestri V, Leslie G, et al. Cancer risks associated with BRCA1 and BRCA2 pathogenic variants. J Clin Oncol. 40(14):1529-1541, 2022.
  6. Engel C, Fischer C, Zachariae S, et al. for the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Breast cancer risk in BRCA1/2 mutation carriers and noncarriers under prospective intensified surveillance. Int J Cancer. 146(4):999-1009, 2020.
  7. 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.
  8. Ho WK, Hassan NT, Yoon SY, et al. Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants – an Asian study of 572 families. Lancet Reg Health West Pac. 44:101017, 2024.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. The Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst. 91(15):1310-1316, 1999.
  17. Yadav S, Boddicker NJ, Na J, et al. Contralateral breast cancer risk among carriers of germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. J Clin Oncol. 41(9):1703-1713, 2023.
  18. 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.
  19. 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.
  20. Begg CB, Haile RW, Borg A, et al. Variation of breast cancer risk among BRCA1/2 carriers. JAMA. 299(2):194-201, 2008.
  21. 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.
  22. 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.
  23. Leongamornlert D, Mahmud N, Tymrakiewicz M, et al. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer. 106(10):1697-701, 2012.
  24. 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.
  25. 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.
  26. 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.
  27. 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 06/06/24

 

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