Mutational Screening of Breast Cancer Susceptibility Gene 1 from Early Onset, Bi-lateral, and Familial Breast Cancer Patients in Taiwan

Chen, Shou‐Tung; Chen, Ruei-A; Kuo, Shou‐Jen; Chien, Yi-Chih

doi:10.1023/a:1021386026051

Cited by 12 publications

(10 citation statements)

References 40 publications

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“…To our knowledge, this is the largest study of BRCA1/2 mutations in Chinese women with familial breast cancer today. The 10.5% of BRCA1/2 mutation rate in this cohort was similar to that of other Chinese series [12,14,15], but we found the BRCA1/2 mutation rate was as high as 23.0% in the subgroup of familial breast cancer patients in whom breast cancer was diagnosed at or before age of 40. The PCR-sequencing assay used in this study is a standard assay to detect BRCA1/2 mutations; this assay cannot detect the large rearrangements of BRCA1/2 genes, such rearrangements may account for 10-15% of BRCA1/2 mutations [16,17].…”

Section: Discussionsupporting

confidence: 89%

“…However, the germline mutations in BRCA1/2 genes in Chinese women with familial breast cancer have not been comprehensively investigated; the frequency of BRCA mutation and pathological characteristics of BRCA tumors from Caucasian women might not be applicable to Chinese women. To date, a few studies are available for investigating BRCA1 and BRCA2 mutations in familial or early onset of breast cancer in Chinese women, many of them may only focus on BRCA1 gene or suffer with a relatively small sample size [12][13][14][15]. The largest one is from east China in which it detected BRCA1/2 mutations in 241 familial and 248 early onset breast cancer patients using single strand conformation polymorphism (SSCP) or denaturing high-performance liquid chromatography (DHPLC) assay [12], these assays may underestimate the mutation rate.…”

Section: Introductionmentioning

confidence: 99%

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Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer

Zhang

Pei

Pang

et al. 2011

Breast Cancer Res Treat

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Although there are some studies to investigate germline mutations in BRCA1/2 genes in Chinese women with familial breast cancer, many of them suffer relatively small sample size. In this study, we screened germline mutations in BRCA1/2 genes in a cohort of 409 Chinese women with familial breast cancer from north China by using a PCR-sequencing assay. A total of 43 deleterious mutations in BRCA1/2 genes were identified in this cohort, including 17 novel mutations and 6 recurrent mutations. The frequencies of BRCA1 and BRCA2 mutations were 3.9% (16/409) and 6.6% (27/409), respectively; the mutation rate of BRCA2 was 1.7-fold higher than that of BRCA1. The entire mutation rate of BRCA1/2 was 10.5% in this cohort; however, the mutation rate of BRCA1/2 genes was 23.0% in 78 familial breast cancer patients whose tumors were diagnosed at or before the age of 40. The mean age at diagnosis of breast cancer in BRCA1 carriers (42.8 years) and BRCA2 carriers (45.1 years) was younger than non-carriers (51.0 years) in this cohort (P = 0.005; P = 0.01, respectively). In addition, both BRCA1 carriers and BRCA2 carriers were more likely to exhibit triple-negative breast cancer (ER-, PgR-, and HER2-) than non-carriers (BRCA1 carriers vs. non-carriers, 69.2 vs. 23.0%, P = 0.001; BRCA2 carriers vs. non-carriers, 45.8 vs. 23.0%, P = 0.01). Our study suggested that the spectrum and characteristics of BRCA1/2 mutations in Chinese familial breast cancer exhibit some unique features, and Chinese women with familial breast cancer whose tumors are diagnosed at or before the age of 40 are good candidates for BRCA1/2 testing.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer

Zhang

Pei

Pang

et al. 2011

Breast Cancer Res Treat

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“…The spectrum of BRCA1 gene mutations in breast cancer patients in various populations has been investigated [5]–[10]. Studies conducted in Taiwan had suggested that the mutation of BRCA1 contributes little to the occurrence of breast cancer [11], [12].…”

Section: Introductionmentioning

confidence: 99%

Methylation of BRCA1 Promoter Region Is Associated with Unfavorable Prognosis in Women with Early-Stage Breast Cancer

et al. 2013

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BRCA1-associated breast cancers are associated with particular features such as early onset, poor histological differentiation, and hormone receptor negativity. Previous studies conducted in Taiwanese population showed that the mutation of BRCA1 gene does not play a significant role in the occurrence of breast cancer. The present study explored methylation of BRCA1 promoter and its relationship to clinical features and outcome in Taiwanese breast cancer patients. Tumor specimens from a cohort of 139 early-stage breast cancer patients were obtained during surgery before adjuvant treatment for DNA extraction. Methylation of BRCA1 promoter region was determined by methylation-specific PCR and the results were related to clinical features and outcome of patients using statistical analysis. Methylation of the BRCA1 promoter was detected in 78 (56%) of the 139 tumors. Chi-square analysis indicated that BRCA1 promoter methylation correlated significantly with triple-negative (ER-/PR-/HER2-) status of breast cancer patients (p = 0.041). The Kaplan-Meier method showed that BRCA1 promoter methylation was significantly associated with poor overall survival (p = 0.026) and disease-free survival (p = 0.001). Multivariate analysis which incorporated variables of patients' age, tumor size, grade, and lymph node metastasis revealed that BRCA1 promoter methylation was associated with overall survival (p = 0.27; hazard ratio, 16.38) and disease-free survival (p = 0.003; hazard ratio, 12.19). Our findings underscore the clinical relevance of the methylation of BRCA1 promoter in Taiwanese patients with early-stage breast cancer.

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“…It is well known that there are significant ethnic disparities between western and eastern countries in terms of breast cancer with respect to cancer incidence, the frequency of BRCA1 and BRCA2 mutation, tumor biology and molecular subtypes [27-29]. In this context, information on the role of serum HER2 ECD in Asian breast cancer women is limited.…”

Section: Introductionmentioning

confidence: 99%

Relationships between serum HER2 ECD, TIMP-1 and clinical outcomes in Taiwanese breast cancer

et al. 2012

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BackgroundSerum levels of the extracellular domain of HER2/neu (HER2 ECD) have been demonstrated to be associated with clinical outcomes. A disintegrin and metalloproteinase-10, a sheddase of HER2/neu, can drive cancer progression and its activity is inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1). However, elevated TIMP-1 expression has been associated with a poor prognosis of breast cancer. Therefore, this study was performed to explore the relationships between serum HER2 ECD, TIMP-1 and clinical outcomes.MethodsOne hundred and eighty-five female breast cancer patients, who received curative mastectomy without neo-adjuvant chemotherapy at Chang-Gung Memorial Hospital, were recruited with informed consent for this study. Pre-operative serum levels of HER2 ECD and TIMP-1 were measured using an enzyme-linked immunosorbent assay.ResultsTwenty-three cases (12.4%) were classified HER2 ECD positive. HER2 ECD positivity was significantly associated with age, lymph node involvement, histological grade, estrogen receptor status, progesterone receptor status, tissue HER2/neu overexpression, and disease-free survival (DFS). In an age, stage, ER and HER2/neu status matched subgroup (N = 41), the serum level of TIMP-1 was significantly associated with HER2 ECD positivity and DFS.ConclusionsA high serum TIMP-1 was significantly associated with HER2 ECD positivity and a poorer DFS among Taiwanese primary breast cancer patients with HER2 overexpression.

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Mutational Screening of Breast Cancer Susceptibility Gene 1 from Early Onset, Bi-lateral, and Familial Breast Cancer Patients in Taiwan

Cited by 12 publications

References 40 publications

Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer

Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer

Methylation of BRCA1 Promoter Region Is Associated with Unfavorable Prognosis in Women with Early-Stage Breast Cancer

Relationships between serum HER2 ECD, TIMP-1 and clinical outcomes in Taiwanese breast cancer

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