title: Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study.
abstract: In spite the close association of the triple-negative breast cancer immunophenotype with hereditary breast cancers and the BRCA1 pathway, there is a lack of population studies that determine the frequency of BRCA1 mutations among triple-negative breast cancer patients. To address this, we have screened a large sample of 403 women diagnosed with triple-negative invasive breast cancer, independently of their age or family history, for germline BRCA1 mutations. Median age at diagnosis was 50 years (range 20-83). The overall prevalence of triple-negative cases among the initial patient group with invasive breast cancer was 8%. BRCA1 was screened by direct DNA sequencing in all patients, including all exons where a mutation was previously found in the Greek population (exons 5, 11, 12, 16, 20, 21, 22, 23, 24-77% of the BRCA1 coding region), including diagnostic PCRs to detect the three Greek founder large genomic rearrangements. Sixty-five deleterious BRCA1 mutations were identified among the 403 triple-negative breast cancer patients (16%). Median age of onset for mutation carriers was 39 years. Among a total of 106 women with early-onset triple-negative breast cancer (<40 years), 38 (36%) had a BRCA1 mutation, while 27% of women with triple-negative breast cancer diagnosed before 50 years (56/208) had a BRCA1 mutation. A mutation was found in 48% (50/105) of the triple-negative breast cancer patients with family history of breast or ovarian cancer. It is noteworthy, however, that of the 65 carriers, 15 (23%) had no reported family history of related cancers. All but one of the carriers had grade III tumors (98%). These results indicate that women with early-onset triple-negative breast cancer, and ideally all triple-negative breast cancer patients, are candidates for BRCA1 genetic testing even in the absence of a family history of breast or ovarian cancer.
authors.affiliation: Molecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research Demokritos, Agia Paraskevi, 15310, Athens, Greece.
authors.forename: Florentia
authors.initials: F
authors.lastname: Fostira
authors.forename: Marianthi
authors.initials: M
authors.lastname: Tsitlaidou
authors.forename: Christos
authors.initials: C
authors.lastname: Papadimitriou
authors.forename: Maroulio
authors.initials: M
authors.lastname: Pertesi
authors.forename: Eleni
authors.initials: E
authors.lastname: Timotheadou
authors.forename: Alexandra V
authors.initials: AV
authors.lastname: Stavropoulou
authors.forename: Stavros
authors.initials: S
authors.lastname: Glentis
authors.forename: Evangelos
authors.initials: E
authors.lastname: Bournakis
authors.forename: Mattheos
authors.initials: M
authors.lastname: Bobos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.forename: Pavlos
authors.initials: P
authors.lastname: Papakostas
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: Helen
authors.initials: H
authors.lastname: Gogas
authors.forename: Pantelis
authors.initials: P
authors.lastname: Skarlos
authors.forename: Epaminontas
authors.initials: E
authors.lastname: Samantas
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Bafaloukos
authors.forename: Paris A
authors.initials: PA
authors.lastname: Kosmidis
authors.forename: Angelos
authors.initials: A
authors.lastname: Koutras
authors.forename: Drakoulis
authors.initials: D
authors.lastname: Yannoukakos
authors.forename: Irene
authors.initials: I
authors.lastname: Konstantopoulou
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D018275:Carcinoma, Lobular / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D018579:Patient Selection; D015995:Prevalence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C492913:BRCA1 protein, human; C508053:ERBB2 protein, human