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 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 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.

By age 70, women who have a BRCA1/2 inherited gene mutation have a 50%-65% chance of getting breast cancer and a 10%-70% chance of getting ovarian cancer [1-2].

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 [1-2].

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)	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
Consortium of Investigators of Modifiers of BRCA1/2 [3]	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 [4]	1,626 BRCA1 mutation carrier families	62% (53%-71%)*			25% (20%-32%)†
Brohet et al. [5]	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 [6-8]	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. [9]	223 BRCA1 mutation carrier families	68% (65%-71%)	60%
Nielsen et al. [10]	181 BRCA1 mutation carrier families	35%	29%
BRCA2
Consortium of Investigators of Modifiers of BRCA1/2 [3]	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 [4]	983 BRCA2 mutation carrier families	43% (32%-56%)*			7% (3%-13%)†
Breast Cancer Linkage Consortium [11-13]	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. [5]	176 BRCA2 mutation carrier families with an average of 4 family members with breast cancer	27% (14%-38%)	6% (2%-11%)
Nielsen et al. [10]	118 BRCA2 mutation carrier families	44%	15%
Population-based studies
CARRIERS study [14]	15,104 Women with breast cancer (801 cases)				23% (16%-33%)‡ (BRCA1) 17% (12%-24%)‡ (BRCA2)
van den Broek et al. [15]	6,294 Dutch women with breast cancer diagnosed before age 55				21% (15%-27%)‡ (BRCA1) 11% (5%-20%)‡ (BRCA2)
EMBRACE [16]	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. [17]	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. [18]	1,008 Ashkenazi Jewish women with breast cancer	69% (BRCA1)  74% (BRCA2)	46% (BRCA1)  12% (BRCA2)
Niell et al. [19]	1,002 Ashkenazi Jewish people with colon cancer			Colon cancer: No excess risk
Leongamornlert et al. [20]	913 British men with prostate cancer			Prostate cancer: 9%¶ (BRCA1)
Tryggvadottir et al. [21]	847 Icelandic women with breast cancer and 2,836 first-degree relatives	46% (BRCA2)
Thorlacius et al. [22]	575 Icelandic women with breast cancer	37% (22%-54%) (BRCA2)
Pooled analyses
International BRCA1/2 Carrier Cohort Study [23]	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. [24]	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 up to age 60.

† Results are for cumulative risk 10 years after the first breast cancer. Cumulative risk 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 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. BRCA1 and BRCA2: Cancer risks and management (PDQ®)–Health professional version. https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-genes-hp-pdq, 2023.
2. American Cancer Society. Ovarian cancer risk factors. https://www.cancer.org/cancer/ovarian-cancer/causes-risks-prevention/risk-factors.html, 2021.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. The Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst. 91(15):1310-1316, 1999.
14. 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.
15. 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.
16. 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.
17. Begg CB, Haile RW, Borg A, et al. Variation of breast cancer risk among BRCA1/2 carriers. JAMA. 299(2):194-201, 2008.
18. 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.
19. 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.
20. Leongamornlert D, Mahmud N, Tymrakiewicz M, et al. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer. 106(10):1697-701, 2012.
21. 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.
22. 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.
23. 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.
24. 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 11/08/23