eprintid: 21808
rev_number: 12
eprint_status: archive
userid: 1589
dir: disk0/00/02/18/08
datestamp: 2016-09-05 09:54:25
lastmod: 2024-03-05 21:26:31
status_changed: 2016-09-05 09:54:25
type: article
metadata_visibility: show
creators_name: Rashid, Muhammad Usman
creators_name: Muhammad, Noor
creators_name: Bajwa, Seerat
creators_name: Faisal, Saima
creators_name: Tahseen, Muhammad
creators_name: Lorenzo Bermejo, Justo
creators_name: Amin, Asim
creators_name: Loya, Asif
creators_name: Hamann, Ute
title: High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients
subjects: ddc-610
divisions: i-850300
divisions: i-911800
abstract: Background: Women harboring BRCA1/2 germline mutations have high lifetime risk of developing breast/ovarian cancer. The recommendation to pursue BRCA1/2 testing is based on patient’s family history of breast/ovarian cancer, age of disease-onset and/or pathologic parameters of breast tumors. Here, we investigated if diagnosis of triple-negative breast cancer (TNBC) independently increases risk of carrying a BRCA1/2 mutation in Pakistan.   Methods: Five hundred and twenty-three breast cancer patients including 237 diagnosed ≤ 30 years of age and 286 with a family history of breast/ovarian cancer were screened for BRCA1/2 small-range mutations and large genomic rearrangements. Immunohistochemical analyses were performed at one center. Univariate and multiple logistic regression models were used to investigate possible differences in prevalence of BRCA1/2 mutations according to patient and tumor characteristics.   Results: Thirty-seven percent of patients presented with TNBC. The prevalence of BRCA1 mutations was higher in patients with TNBC than non-TNBC (37% vs. 10%, P < 0.0001). 1% of TNBC patients were observed to have BRCA2 mutations. Subgroup analyses revealed a larger proportion of BRCA1 mutations in TNBC than non-TNBC among patients 1) diagnosed at early-age with no family history of breast/ovarian cancer (14% vs. 5%, P = 0.03), 2) diagnosed at early-age irrespective of family history (28% vs. 11%, P = 0.0003), 3) had a family history of breast cancer (49% vs. 12%, P < 0.0001), and 4) those with family history of breast and ovarian cancer (81% vs. 28%, P = 0.0005). TNBC patients harboring BRCA1 mutations were diagnosed at a later age than non-carriers (median age at diagnosis: 30 years (range 22–53) vs. 28 years (range 18–67), P = 0.002). The association between TNBC status and presence of BRCA1 mutations was independent of the simultaneous consideration of family phenotype, tumor histology and grade in a multiple logistic regression model (Ratio of the probability of carrying BRCA1/2 mutations for TNBC vs. non-TNBC 4.23; 95% CI 2.50–7.14; P < 0.0001).   Conclusion: Genetic BRCA1 testing should be considered for Pakistani women diagnosed with TNBC.
date: 2016
publisher: BioMed Central; Springer
id_scheme: DOI
ppn_swb: 1658589726
own_urn: urn:nbn:de:bsz:16-heidok-218086
language: eng
bibsort: RASHIDMUHAHIGHPREVAL2016
full_text_status: public
publication: BMC Cancer
volume: 16
number: 673
place_of_pub: London; Berlin; Heidelberg
pagerange: 1-10
issn: 1471-2407
citation:   Rashid, Muhammad Usman ; Muhammad, Noor ; Bajwa, Seerat ; Faisal, Saima ; Tahseen, Muhammad ; Lorenzo Bermejo, Justo ; Amin, Asim ; Loya, Asif ; Hamann, Ute  (2016) High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients.  BMC Cancer, 16 (673).  pp. 1-10.  ISSN 1471-2407     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/21808/1/12885_2016_Article_2698.pdf