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Genetics of Breast and Ovarian Cancer (PDQ®)
Health Professional Version   Last Modified: 12/23/2008
Table 2. Studies of Cancer Penetrance Among BRCA1 and BRCA2 Mutation Carriers: Cumulative Incidence of Breast Cancer

  Cumulative Incidence of Breast Cancer to Given Age 
BRCA1 BRCA2 BRCA1/2
Population 50 yr 70 yr 50 yr 70 yr 50 yr 70 yr
Linkage analysis-maximization of logarithm of the odd (LOD) score
—214 breast-ovary families (BCLC) [15] 59% 82%
BRCA1-linked families (BCLC) [56] 51% 85%
—237 breast and breast-ovarian cancer families (BCLC) [58] 49% 71% 28% 84%
Incidence of second cancers after breast cancer
—33 BRCA1-linked families (BCLC) [55] 73% 87%
—BRCA1-linked families (BCLC) [56] 50% 65%
Analysis of family members
—Jewish ovarian cancer cases, 7 BRCA1, 3 BRCA2 [57] 30%a 50%a 16%a 23%a
—Jewish breast-ovary families, 16 BRCA1, 9 BRCA2 [57] 37%a 64%a 18%a 49%a
Kin cohort using family and cancer registries
—Unselected Icelandic breast cancer patients, 56 female and 13 male BRCA2 995del5 [59] 17% 37%
Second or contralateral cancer incidence; focus was on nonbreast and ovary outcomes
—173 breast-ovarian cancer families either BRCA2-positive or BRCA2-linked (BCLC) [12] 37% 52%
Modified segregation analysis - all available relatives tested (MENDEL)
—Australian population-based breast cancer, aged <40 years, 9 BRCA1, 9 BRCA2 [60] 10% 40%
Kin cohort
—Community-based Washington, D.C. area Jews, 61 BRCA1, 59 BRCA2 [46] 38% 59% 26% 51% 33% 56%
—Jewish women with breast cancer, 34 BRCA1, 15 BRCA2 [61] 60% 28%
—Jewish women with ovarian cancer, 44 BRCA1, 24 BRCA2 [64] 31%b 44%c 6%b 37%c
—Unselected cases ovarian cancer, 39 BRCA1, 21 BRCA2 [42] 68%d 14%d
Modified segregation analysis (MENDEL)
—Breast cancer cases, aged <55 years, 8 BRCA1, 16 BRCA2 [62] 32% 47% 18% 56% 21% 54%
—Families with 2+ cases ovarian cancer, 40 BRCA1, 11 BRCA2 [63] 39% 72% 19% 71%
—Unselected cases ovarian cancer, 12 BRCA1 [63] 34% 50%
—164 BRCA2-positive families from BCLC [66] 41%
—Unselected cases ovarian or breast cancer from 22 studies, 289 BRCA1, 221 BRCA2 [68] 38% 65% 15% 45%
—Australian multiple-case families, 28 BRCA1, 23 BRCA2 [69] 48% 74%
Relative risk times population rates
—Jewish hospital-based ovarian cancer patients, 103 BRCA1, 44 BRCA2 founder mutations [65] 18% 59% 6% 38%
Direct Kaplan-Meier estimates restricted to relatives known to be mutation positive
—Unselected Jewish breast cancer patients from NY, 67 BRCA1, 37 BRCA2 [43] 39% 69% 34% 74%
Mendelian retrospective likelihood approach
—U.S.-based through the Cancer Genetics Network, most counseling clinic-based, although smaller number population-based, 238 BRCA1, 143 BRCA2 [70] 46% 43%

aOutcome is breast OR ovarian cancer.
bIncidence to age 55 years.
cIncidence to age 75 years.
dIncidence to age 80 years.

References

  1. Cancer risks in BRCA2 mutation carriers. The Breast Cancer Linkage Consortium. J Natl Cancer Inst 91 (15): 1310-6, 1999.  [PUBMED Abstract]

  2. Easton DF, Bishop DT, Ford D, et al.: 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.  [PUBMED Abstract]

  3. Risch HA, McLaughlin JR, Cole DE, et al.: Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68 (3): 700-10, 2001.  [PUBMED Abstract]

  4. King MC, Marks JH, Mandell JB, et al.: Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302 (5645): 643-6, 2003.  [PUBMED Abstract]

  5. Struewing JP, Hartge P, Wacholder S, et al.: The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336 (20): 1401-8, 1997.  [PUBMED Abstract]

  6. Ford D, Easton DF, Bishop DT, et al.: Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 343 (8899): 692-5, 1994.  [PUBMED Abstract]

  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): 265-71, 1995.  [PUBMED Abstract]

  8. Levy-Lahad E, Catane R, Eisenberg S, et al.: Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. Am J Hum Genet 60 (5): 1059-67, 1997.  [PUBMED Abstract]

  9. Ford D, Easton DF, Stratton M, et al.: Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 62 (3): 676-89, 1998.  [PUBMED Abstract]

  10. 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.  [PUBMED Abstract]

  11. Hopper JL, Southey MC, Dite GS, et al.: Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study. Cancer Epidemiol Biomarkers Prev 8 (9): 741-7, 1999.  [PUBMED Abstract]

  12. 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): 1241-7, 1999.  [PUBMED Abstract]

  13. Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Anglian Breast Cancer Study Group. Br J Cancer 83 (10): 1301-8, 2000.  [PUBMED Abstract]

  14. Antoniou AC, Gayther SA, Stratton JF, et al.: Risk models for familial ovarian and breast cancer. Genet Epidemiol 18 (2): 173-90, 2000.  [PUBMED Abstract]

  15. Moslehi R, Chu W, Karlan B, et al.: BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. Am J Hum Genet 66 (4): 1259-72, 2000.  [PUBMED Abstract]

  16. Satagopan JM, Offit K, Foulkes W, et al.: The lifetime risks of breast cancer in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev 10 (5): 467-73, 2001.  [PUBMED Abstract]

  17. Thompson D, Easton D; Breast Cancer Linkage Consortium.: Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet 68 (2): 410-9, 2001.  [PUBMED Abstract]

  18. Antoniou A, Pharoah PD, Narod S, et al.: Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72 (5): 1117-30, 2003.  [PUBMED Abstract]

  19. Scott CL, Jenkins MA, Southey MC, et al.: Average age-specific cumulative risk of breast cancer according to type and site of germline mutations in BRCA1 and BRCA2 estimated from multiple-case breast cancer families attending Australian family cancer clinics. Hum Genet 112 (5-6): 542-51, 2003.  [PUBMED Abstract]

  20. Chen S, Iversen ES, Friebel T, et al.: Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol 24 (6): 863-71, 2006.  [PUBMED Abstract]


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