title: A multi-institutional study on the association between BRCA1/BRCA2 mutational status and triple-negative breast cancer in familial breast cancer patients.
abstract: Triple-negative breast cancer (TNBC) accounts for 12-24 % of all breast cancers. Here, we studied 221 familial breast and/or ovarian cancer patients from 37 hospitals using a comprehensive approach to identify large genomic rearrangements (LGRs) as well as sequence variants, and investigated the association between BRCA1/2 mutational status and TNBC. We performed direct sequencing or mutation scanning followed by direct sequencing. Then, 143 BRCA1/2 mutation-negative patients were screened for LGRs. In this study, the prevalence of BRCA1/2 mutations was high (36.9 %). The prevalence of BRCA1 mutations was similar to that of BRCA2 mutations: 49.4 versus 50.6 %, respectively. TNBC was diagnosed in 35.2 % of BRCA1/2 mutation carriers and 57.1 % of BRCA1 mutation carriers. Conversely, two-thirds of TNBC patients carried BRCA1/2 mutation(s), and about half were BRCA1 mutation carriers. When stratified by the mutated gene, TNBC prevalence in BRCA1 mutation carriers was significantly lower when there was a family history of ovarian cancer. Our multinomial logistic regression model demonstrated that no single factor was sufficient, and at least two factors, such as a patient with family history of both breast cancer and ovarian cancer or a patient diagnosed at a relatively young age (<40 years) with a TNBC phenotype, are necessary to indicate BRCA1/2 genetic testing in this population. Our results suggest that TNBC is a strong predictor for the presence of a BRCA1 mutation in this population, but additional risk factors should also be evaluated to ascertain a 10 % or higher prior probability of BRCA1/2 mutation testing.
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea, mwseong@gmail.com.
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Kim
authors.forename: Il Yong
authors.initials: IY
authors.lastname: Chung
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Kang
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
authors.forename: Min Hyuk
authors.initials: MH
authors.lastname: Lee
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Son
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Park
authors.forename: Sung Im
authors.initials: SI
authors.lastname: Cho
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000328:Adult; D017668:Age of Onset; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics; D015995:Prevalence; D011379:Prognosis; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D064726:Triple Negative Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D055815:Young Adult