title: Does the age of breast cancer diagnosis in first-degree relatives impact on the risk of breast cancer in BRCA1 and BRCA2 mutation carriers?
abstract: The purpose of this study is to estimate the age-specific annual risks of breast cancer in a woman with a germline BRCA mutation and an affected first-degree relative according to the age of breast cancer diagnosis in the relative. Women with BRCA mutations with no previous diagnosis of breast cancer and with one first-degree relative with breast cancer were followed for breast cancers for a mean of 5.9 years (minimum 2 years). Age-specific annual breast cancer risks were calculated, according to the age of breast cancer diagnosis in the proband and the first-degree relative. 1114 cancer-free women with a BRCA mutation with a single first-degree relative with breast cancer were eligible for the study. 122 women (11.0 %) were diagnosed with incident breast cancer. The annual risk of breast cancer was 2.0 % for women with BRCA1 mutations and was 1.6 % for women with BRCA2 mutations. The age of breast cancer diagnosis in the first-degree relative did not affect the annual breast cancer risks for BRCA1 mutation carriers. For BRCA2 mutation carriers, the annual breast cancer risk was 4.5 % for women with a first-degree relative diagnosed with breast cancer under the age of 30 years and was 0.7 % for women with a relative diagnosed over the age of 60. Among women with BRCA2 mutations, a family history of early-onset breast cancer is a risk factor for developing breast cancer. Risk assessment for healthy BRCA2 mutation carriers should consider the ages of breast cancers diagnosed in first-degree relatives.
authors.forename: John
authors.initials: J
authors.lastname: Semple
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Metcalfe
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.forename: Susan
authors.initials: S
authors.lastname: Armel
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Beth
authors.initials: B
authors.lastname: Karlan
authors.forename: William
authors.initials: W
authors.lastname: Foulkes
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Javaid
authors.initials: J
authors.lastname: Iqbal
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005190:Family; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein