Familial Breast Cancer
A family history of breast cancer has been consistently recognized as one of the most important risk factors for the disease. Various studies have suggested that between 15-25% of women with breast cancer have at least one first- or second-degree relative who also has breast cancer. A woman with an affected first-degree relative has from 1.5-2.5 times the breast cancer risk of a woman without a family history of breast cancer. Within the group of women with a family history of breast cancer, those with multiple affected relatives are at higher risk, as are those with relatives affected at younger ages.
Risk is also higher in some, but not all, series if one or more of the affected relatives has had bilateral disease. Because relative risk figures may be difficult to translate in a meaningful way when performing clinical risk counseling, empirical models have been developed that can be used to provide women with an estimated percentage risk of developing breast cancer over a defined time period. The best known models are the “Claus tables” and the Gail model.
The “Claus tables” derive from the Cancer and Steroid Hormone Study (CASH) dataset, and only use family history data to generate risk figures.
The Gail model, generated from the Breast Cancer Detection Demonstration Project dataset, incorporates reproductive and clinical variables in addition to a history of breast cancer in first-degree relatives (mothers and sisters). Both models are useful, but have significant limitations when used to estimate individual cancer risks.
Mark E. Robson
Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst 2003
- Newman B, Austin MA, Lee M et al. Inheritance of human breast cancer: Evidence for autosomal dominant transmission in high-risk families. Proc Natl Acad Sci USA 1988; 85:3044-3048.
- Hall JM, Lee MK, Newman B et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990; 250:1684-1689.
- Narod SA, Feunteun J, Lynch HT et al. Familial breast-ovarian cancer locus on chromosome 17q12-q23. Lancet 1991; 338:82-83.
- Steichen-Gersdorf E, Gallion HH, Ford D et al. Familial site-specific ovarian cancer is linked to BRCA1 on 17q12-21. Am J Hum Genet 1994; 55:870-875.
- Miki Y, Swensen J, Shattuck-Eidens D et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994; 266:66-71.
- Wooster R, Neuhausen SL, Mangion J et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 1994; 265:2088-2090.
- Wooster R, Bignell G, Lancaster J et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995; 378:789-792.
- Zhang H, Tombline G, Weber BL. BRCA1, BRCA2, and DNA damage response: Collision or collusion? Cell 1998; 92:433-436.
- Malone KE, Daling JR, Thompson JD et al. BRCA1 mutations and breast cancer in the general population: Analyses in women before age 35 years and in women before age 45 years with first-degree family history. JAMA 1998; 279:922-929.
- Newman B, Mu H, Butler LM, Millikan RC et al. Frequency of breast cancer attributable to BRCA1 in a population-based series of American women. JAMA 1998; 279:915-921.
- Berchuck A, Heron KA, Carney ME et al. Frequency of germline and somatic
- BRCA1 mutations in ovarian cancer. Clin Cancer Res 1998; 4:2433-2437.
- Rubin SC, Blackwood MA, Bandera C et al. BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: Relationship to family history and implications for genetic testing. Am J Obstet Gynecol 1998; 178:670-677.
- Stratton JF, Gayther SA, Russell P et al. Contribution of BRCA1 mutations to ovarian cancer. N Engl J Med 1997; 336:1125-1130.
- Szabo CI, King MC. Population genetics of BRCA1 and BRCA2. Am J Hum Genet 1997; 60:1013-1020.
- Ford D, Easton DF, Stratton M et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer Families. Am J Hum Genet.1998; 62:676-689.
- Tonin P, Weber B, Offit K et al. Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med 1996; 2:1179-1183.
- 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 1997; 336:1401-1408.
- Kleihues P, Schauble B, Zur HA et al. Tumors associated with p53 germline mutations: A synopsis of 91 families. Am J Pathol 1997; 150:1-13.
- Schrager CA, Schneider D, Gruener AC et al. Clinical and pathological features of breast disease in Cowden's syndrome: An underrecognized syndrome with an increased risk of breast cancer. Hum Pathol 1998; 29:47-53.
- Anonymous. Pathology of familial breast cancer: Differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Breast Cancer Linkage Consortium. Lancet 1997; 349:1505-1510.
- Watson P, Marcus JN, Lynch HT. Prognosis of BRCA1 hereditary breast cancer. Lancet 1998; 351:304-305.
- Burke W, Daly M, Garber J et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium. JAMA 1997; 277:997-1003.
- Eisinger F, Alby N, Bremond A et al. Recommendations for medical management of hereditary breast and ovarian cancer: The French National Ad Hoc Committee. Ann Oncol 1998; 9:939-950.
- Hartmann LC, Schaid DJ, Woods JE et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999; 340:77-84.
- Grann VR, Panageas KS, Whang W et al. Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1- positive or BRCA2-positive patients. J Clin Oncol 1998; 16:979-985.
- Schrag D, Kuntz KM, Garber JE et al. Decision analysis - effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 or BRCA2 mutations. N Engl J Med 1997; 336:1465-1471.
- Fisher B, Costantino JP, Wickerham DL et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998; 90:1371-1388.
- Narod SA, Risch H, Moslehi R et al. Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med. 1998; 339:424-428.
- Robson M, Levin D, Federici M et al. Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst 1999; 91:2112-2117.