High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients

BMC Cancer

Research Article

Ute Hamann¹  Justo Lorenzo Bermejo²  Asim Amin³  Saima Faisal⁴  Muhammad Tahseen⁴  Asif Loya⁴  Seerat Bajwa⁴  Noor Muhammad⁴  Muhammad Usman Rashid⁵ 

[1] German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, Germany;Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany;Levine Cancer Institute (LCI), Charlotte, USA;Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan;Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan;German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, Germany;

关键词: BRCA1/2;    Breast cancer;    Germline mutations;    Pakistan;    Triple-negative breast cancer;   

DOI  :  10.1186/s12885-016-2698-y

 received in 2016-04-06, accepted in 2016-08-09,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundWomen 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.MethodsFive 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.ResultsThirty-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).ConclusionGenetic BRCA1 testing should be considered for Pakistani women diagnosed with TNBC.

【 授权许可】

CC BY   
© The Author(s). 2016