Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study (Journal article)

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.

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
URI: https://olympias.lib.uoi.gr/jspui/handle/123456789/19103
ISSN: 1573-7217
Link: http://www.ncbi.nlm.nih.gov/pubmed/22434525
http://www.springerlink.com/content/c7nw54057522n876/fulltext.pdf
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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