TY  - JOUR
VL  - 16
ID  - heidok21808
JF  - BMC Cancer
TI  - High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients
Y1  - 2016///
SN  - 1471-2407
AV  - public
N2  - 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.
SP  - 1
EP  - 10
PB  - BioMed Central; Springer
A1  - Rashid, Muhammad Usman
A1  - Muhammad, Noor
A1  - Bajwa, Seerat
A1  - Faisal, Saima
A1  - Tahseen, Muhammad
A1  - Lorenzo Bermejo, Justo
A1  - Amin, Asim
A1  - Loya, Asif
A1  - Hamann, Ute
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/21808/
IS  - 673
CY  - London; Berlin; Heidelberg
ER  -