title: Contribution of BRCA1 and BRCA2 germ-line mutations to the incidence of breast cancer in young women: results from a prospective population-based study in France.
abstract: The prevalence of BRCA1/2 germ-line mutations was assessed in a prospective population-based series of early-onset breast cancer (BC) patients in France, and the usefulness of a clinical assessment of hereditary BC risk, based on multiple criteria including pedigree structure, was evaluated. Through the Rhone region BC registry, 232 women diagnosed with BC before 46 years of age were included. They were tested for BRCA1/2 mutations an average of 10 months after diagnosis. All the women were classified according to their family history of cancer: high risk of hereditary breast cancer (HBC), low risk of HBC, isolated BC, and unknown HBC risk. Deleterious mutations were observed in 21 women (9.1%): 15 (6.5%) BRCA1 and 6 (2.6%) BRCA2. Mutations were more prevalent in women who developed BC before age 41 than in women who developed BC between ages 41 and 45 (12.8% versus 5.2%, respectively, P = 0.04). A high prevalence of BRCA1/2 mutations was found among women in the high-risk category with particular family features (i.e., small family size, predominantly male pedigree, specific cancers; 23.5%) and among women with isolated BC before age 41 and with five or fewer close adult female relatives (16.6%). According to the 10% probability level recommended by the American Society of Clinical Oncology guidelines for genetic testing of cancer, BRCA1/2 mutation screening should be considered for all women diagnosed before age 41, except for those with isolated BC in a large pedigree including multiple unaffected female relatives. The clinical assessment of HBC risk that we have developed should help in the decision to perform genetic testing.
authors.affiliation: Department of Public Health, Cancer Centre Léon Bérard, Lyon, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Bonadona
authors.forename: Olga M
authors.initials: OM
authors.lastname: Sinilnikova
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chopin
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Hervé
authors.initials: H
authors.lastname: Mignotte
authors.forename: Patrice
authors.initials: P
authors.lastname: Mathevet
authors.forename: Alain
authors.initials: A
authors.lastname: Brémond
authors.forename: Alain
authors.initials: A
authors.lastname: Martin
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Bobin
authors.forename: Pascale
authors.initials: P
authors.lastname: Romestaing
authors.forename: Daniel
authors.initials: D
authors.lastname: Raudrant
authors.forename: René-Charles
authors.initials: RC
authors.lastname: Rudigoz
authors.forename: Mélanie
authors.initials: M
authors.lastname: Léoné
authors.forename: Franck
authors.initials: F
authors.lastname: Chauvin
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Lenoir
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
mesh_terms: D000293:Adolescent; D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005602:France; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D010375:Pedigree; D019683:Penetrance; D011446:Prospective Studies; D012306:Risk