scholarly journals Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test

2020 ◽  
Vol 52 (3) ◽  
pp. 697-713
Author(s):  
Hee-Chul Shin ◽  
Han-Byoel Lee ◽  
Tae-Kyung Yoo ◽  
Eun-Shin Lee ◽  
Ryong Nam Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Features ◽  
Germline Mutations ◽  
Gene Panel ◽  
Hereditary Cancer Syndrome ◽  
Deleterious Mutations ◽  
Breast Cancer Patients ◽  
Cancer Syndrome ◽  
Multiple Gene

PurposeHereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC).Materials and MethodsA total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017.ResultsOf 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had <i>BRCA1/2</i> mutations and 38 patients (40.0%) had non-<i>BRCA1/2</i> mutations. We detected two novel deleterious mutations in <i>BRCA2</i> and <i>MLH1</i>.ConclusionNGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.

scholarly journals P4: CIRCULATING MIRNA PROFILES POINT TO DYSREGULATION IN TGFBETA/SMAD3 TUMOR SUPPRESSOR SIGNATURE IN BRCA POSITIVE BREAST CANCER PATIENTS

2016 ◽  
Vol 64 (3) ◽  
pp. 818.2-818
Author(s):  
I Shapira ◽  
T Bhuiya ◽  
S Arora ◽  
N Mukhi ◽  
S Datla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Real Time ◽  
Cancer Patients ◽  
Survival Data ◽  
Real Time Pcr ◽  
Germ Line ◽  
Germline Mutations ◽  
Breast Cancer Patients ◽  
Mean Differences

Purpose of StudyOver 240,000 individuals are diagnosed with breast cancer (BrCa) of which 12,000 individuals carry BRCA germline mutations. MicroRNA dysregulation is common in malignancy and may correlate with germline mutations.Aims:1. Analyze microRNAs in patients with breast cancer with or without BRCA germ line mutations, with and without cancer.2. Identify molecular BRCA mutant patients to deduct reasons for accelerated malignancy.Methods UsedWe analyzed plasma miR expression from 94 br cancer patients (41 BRCA positive) relative to 24 normal controls. All samples were collected between 2010 and 2014 and survival data was known for all cancer patients. TaqMan Open Array panel was used to simultaneously run hundreds of microRNA assays in the Applied Biosystem Open array real time PCR. Using AB open array real time PCR, 756 miRNA species were detected. Two-sample t-test was used for all 2-sample comparison and ANOVA followed by Tukey HSD post-hoc test to compare the miRs mean differences. All tests were 2-tailed and results with a p<0.05 were considered statistically significant.Summary of ResultsBRCA+underexpressed hsa-mir-10a and hsa-mir-376c and over-expressed Hsa- mir- 326 and Hsa-mir-143 relative to BRCA-; p<0.05.Using Coremine data mining linking genes and diseases differentially expressed circulating miRs are linked to tumor suppressor TGFbeta/SMAD3.ConclusionsThe early onset of breast cancer in BRCA mutant patients may recapitulate the pro-oncogenic effects of TGF-β. The context dependent SMAD3 binding & tumor suppression TGF-β effects are abrogated in BRCA mutant patients. TGF-β/Smad3 tumor-suppressor signature suppresses local inflammation in the tumor microenvironment.

Identification and analysis of CHEK2 germline mutations in Chinese BRCA1/2-negative breast cancer patients

2018 ◽  
Vol 169 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Zhenhua Fan ◽  
Tao Ouyang ◽  
Jinfeng Li ◽  
Tianfeng Wang ◽  
Zhaoqing Fan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Germline Mutations ◽  
Breast Cancer Patients

Serum ANGPTL2 Levels Reflect Clinical Features of Breast Cancer Patients: Implications for the Pathogenesis of Breast Cancer Metastasis

2014 ◽  
Vol 29 (3) ◽  
pp. 239-245 ◽  
Author(s):  
Motoyoshi Endo ◽  
Yutaka Yamamoto ◽  
Masahiro Nakano ◽  
Tetsuro Masuda ◽  
Haruki Odagiri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Features ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Ductal Carcinoma ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Patients

Introduction Breast cancer is a leading cause of cancer-related death in women worldwide, and its metastasis is a major cause of disease mortality. Therefore, identification of the mechanisms underlying breast cancer metastasis is crucial for the development of therapeutic and diagnostic strategies. Our recent study of immunodeficient female mice transplanted with MDA-MB231 breast cancer cells demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates metastasis through both increasing tumor cell migration in an autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum ANGPTL2 levels reflect the clinical features of breast cancer progression. Methods We monitored the levels of secreted ANGPTL2 in supernatants of cultured proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2 levels were positively correlated with cancer progression in an in vivo breast cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether serum ANGPTL2 levels were associated with clinical features in breast cancer patients. Results Both in vitro and in vivo experiments showed that the levels of ANGPTL2 secreted from breast cancer cells increased with cell proliferation and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast cancer were significantly higher than those in healthy subjects or in patients with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum ANGPTL2 levels in patients negative for estrogen receptors and progesterone receptors, particularly triple-negative cases, reflected histological grades. Conclusions These findings suggest that serum ANGPTL2 levels in breast cancer patients could represent a potential marker of breast cancer metastasis.

Spectrum and clinical relevance of PALB2 germline mutations in 7657 Chinese BRCA1/2-negative breast cancer patients

2019 ◽  
Vol 179 (3) ◽  
pp. 605-614
Author(s):  
Yifan Wu ◽  
Tao Ouyang ◽  
Jinfeng Li ◽  
Tianfeng Wang ◽  
Zhaoqing Fan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Relevance ◽  
Germline Mutations ◽  
Breast Cancer Patients

Local-regional relapse and distant metastasis in conservatively managed triple negative early stage breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 594-594
Author(s):  
B. G. Haffty ◽  
Q. Yang ◽  
M. Reiss ◽  
T. Kearney ◽  
W. Hait ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Data Base ◽  
Cancer Patients ◽  
Distant Metastasis ◽  
Triple Negative ◽  
Deleterious Mutations ◽  
Breast Cancer Patients ◽  
Free Rate ◽  
Cause Specific Survival

594 Background: Triple negative (TN) basal-like breast cancers (Negative for ER,PR,HER2/neu) represent an aggressive phenotype, with unique clinical and pathologic features. The purpose of this study was to determine the prognostic significance of this classification with respect to local-regional relapse and distant metastasis in a cohort of conservatively managed breast cancer patients. Methods: A large data base of conservatively managed breast cancer patients with long term follow-up, in which all three immunhistochemical markers, ER,PR and HER2/neu were available was reviewed. Patients were classified as TN if they tested negative for all three markers. Of 442 patients in the data base with all three markers available, 100 were classified as TN. All clinical, pathologic, outcomes and molecular marker data were entered into a computerized database. Results: As of September 2005, with a median follow-up of 7 years, of the 442 patients in the study there have been 50 in-breast relapses, 10 nodal relapses, 68 distant relapses and 62 deaths. Compared with the other subtypes, the TN cohort had a poorer overall survival (67% vs 75%, p = .096), poorer distant metastasis-free rate (61% vs 75%, p = .002), poorer cause-specific survival (67% vs 78%, p = .03), and poorer nodal relapse-free rate (93% vs 99%, p = .021). In a multivariate Cox regression analysis, TN subtype was an independent predictor of distant metastasis (HR=2.6, CI 1.53–4.35, p = .004) and cause- specific survival (HR= 2.36, CI 1.28–4.38, p= .006). There was no significant difference in local (in-breast) control between the TN and other subtypes. BRCA testing was performed on 85 patients in this cohort, of whom 8 had deleterious mutations in BRCA1 and 6 had deleterious mutations in BRCA2. Of 8 BRCA1 mutant patients 7 were classified as TN, while only 1 of 6 BRCA2 patients were TN (p < .001). Conclusions: Patients classified as TN have a poor prognosis with respect to overall, disease free and cause specific survival. However there was no evidence that these patients are at higher risk for local relapse following conservative surgery and radiation. BRCA1 mutant patients develop predominantly TN tumors. No significant financial relationships to disclose.

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