Τίτλος:
Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: Implications for genetic screening selection criteria: A Hellenic Cooperative Oncology Group Study
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2012 Springer Science+Business Media, LLC.
Συγγραφείς:
Fostira, F.
Tsitlaidou, M.
Papadimitriou, C.
Pertesi, M.
Timotheadou, E.
Stavropoulou, A.V.
Glentis, S.
Bournakis, E.
Bobos, M.
Pectasides, D.
Papakostas, P.
Pentheroudakis, G.
Gogas, H.
Skarlos, P.
Samantas, E.
Bafaloukos, D.
Kosmidis, P.A.
Koutras, A.
Yannoukakos, D.
Konstantopoulou, I.
Fountzilas, G.
Περιοδικό:
Breast Cancer Research and Treatment
Λέξεις-κλειδιά:
adult; age; aged; article; cancer invasion; controlled study; DNA sequence; exon; family history; female; gene frequency; gene mutation; gene rearrangement; genetic screening; Greece; heterozygote; human; human tissue; major clinical study; oncogene; onset age; ovary cancer; polymerase chain reaction; prevalence; priority journal; triple negative breast cancer, Adult; Aged; Aged, 80 and over; BRCA1 Protein; Carcinoma, Ductal, Breast; Carcinoma, Lobular; DNA Mutational Analysis; Female; Genetic Testing; Hereditary Breast and Ovarian Cancer Syndrome; Heterozygote; Humans; Middle Aged; Mutation; Patient Selection; Prevalence; Receptor, erbB-2; Receptors, Estrogen; Receptors, Progesterone; Young Adult
DOI:
10.1007/s10549-012-2021-9
