Analysis of large deletions in <Emphasis Type="Italic">BRCA1</Emphasis>, <Emphasis Type="Italic">BRCA2</Emphasis> and <Emphasis Type="Italic">PALB2</Emphasis> genes in Finnish breast and ovarian cancer families

Background  

BRCA1 and BRCA2 are the two most important genes associated with familial breast and ovarian cancer susceptibility. In addition, PALB2 has recently been identified as a breast cancer susceptibility gene in several populations. Here we have evaluated whether large genomic rearrangement in these genes could explain some of Finnish breast and/or ovarian cancer families.     

Impact of <Emphasis Type="Italic">UGT2B7</Emphasis><Superscript><Emphasis Type="Italic">His268Tyr</Emphasis></Superscript> polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer

Introduction  

Epirubicin is a common adjuvant treatment for breast cancer. It is mainly eliminated after glucuronidation through uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7). The present study aimed to describe the impact of the UGT2B7 ^His268Tyr polymorphism on invasive disease-free survival in breast cancer patients after epirubicin treatment.     

Haplotype analysis of common variants in the <Emphasis Type="Italic">BRCA1</Emphasis> gene and risk of sporadic breast cancer

Introduction  

Truncation mutations in the BRCA1 gene cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population and account for little of the overall incidence of sporadic breast cancer.     

Promoter hypermethylation of the <Emphasis Type="Italic">SFRP2</Emphasis> gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer

Background  

We have previously reported that expression of the Wnt antagonist genes SFRP1 and SFRP5 is frequently silenced by promoter hypermethylation in breast cancer. SFRP2 is a further Wnt inhibitor whose expression was recently found being downregulated in various malignancies. Here we investigated whether SFRP2 is also implicated in human breast cancer, and if so whether SFRP2 promoter methylation might serve as a potential tumor biomarker.     

Variants in estrogen-biosynthesis genes <Emphasis Type="Italic">CYP17</Emphasis> and <Emphasis Type="Italic">CYP19</Emphasis> and breast cancer risk: a family-based genetic association study

Background  

Case-control studies have reported inconsistent results concerning breast cancer risk and polymorphisms in genes that control endogenous estrogen biosynthesis. We report findings from the first family-based association study examining associations between female breast cancer risk and polymorphisms in two key estrogen-biosynthesis genes CYP17 (T→C promoter polymorphism) and CYP19 (TTTA repeat polymorphism).     

Breast cancer oestrogen independence mediated by <Emphasis Type="Italic">BCAR1</Emphasis> or <Emphasis Type="Italic">BCAR3</Emphasis> genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway

Introduction  

Tamoxifen is effective for endocrine treatment of oestrogen receptor-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing oestrogen-independent proliferation. The BCAR1 and BCAR3 genes both encode components of intracellular signal transduction, but their direct effect on breast cancer cell proliferation is not known. The aim of this study was to investigate the growth control mediated by these BCAR genes by gene expression profiling.     

<Emphasis Type="Italic">In vivo</Emphasis> measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

Background  

Angiogenesis, crucial for tumor progression, is a process regulated in the tissue micro-environment. Vascular endothelial growth factor (VEGF) is a potent stimulatory factor of angiogenesis and a negative prognostic indicator of breast cancer. VEGF is biologically active in the extracellular space and hitherto, there has been a lack of techniques enabling sampling of angiogenic molecules such as VEGF in situ. The majority of breast cancers are estrogen-dependent, and estrogen has been shown to regulate VEGF in normal breast tissue and experimental breast cancer. We investigated if microdialysis may be applicable in human breast cancer for sampling of extracellular VEGF in situ and to explore if there is an association with local estradiol and VEGF levels in normal and cancerous breast tissue.     

<Emphasis Type="Italic">ErbB3</Emphasis> is required for ductal morphogenesis in the mouse mammary gland

Introduction  

The receptor ErbB3/HER3 is often over-expressed in human breast cancers, frequently in conjunction with over-expression of the proto-oncogene ERBB2/HER2/NEU. Although the prognostic/predictive value of ErbB3 expression in breast cancer is unclear, ErbB3 is known to contribute to therapeutic resistance. Understanding ErbB3 functions in the normal mammary gland will help to explain its role in cancer etiology and as a modulator of signaling responses to the mammary oncogene ERBB2.     

Long-term prognostic significance of HER-2/<Emphasis Type="Italic">neu</Emphasis> in untreated node-negative breast cancer depends on the method of testing

Introduction  

The prognostic significance of HER-2/neu in breast cancer is a matter of controversy. We have performed a study in 101 node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting, and analysed the prognostic significance of immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), both separately and in combination, in comparison with traditional prognostic factors.     

Breast tumors from <Emphasis Type="Italic">CHEK2 1100delC-</Emphasis> mutation carriers: genomic landscape and clinical implications

Introduction  

Checkpoint kinase 2 (CHEK2) is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about twofold. We investigated gene copy-number aberrations and gene-expression profiles that are typical for breast tumors of CHEK2 1100delC-mutation carriers.     

Association of <Emphasis Type="Italic">CTLA-4</Emphasis> gene polymorphisms with sporadic breast cancer in Chinese Han population

Background  

The host immunogenetic background plays an important role in the development of breast cancer. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a molecule expressed predominantly on activated T cells and is important during the down-regulation of T-cell activation. To evaluate the potential influences of CTLA-4 gene polymorphisms on breast cancer risk, a case-control study was conducted in Han women of Northeast China.     

Low incidence of methylation of the promoter region of the <Emphasis Type="Italic">FANCF</Emphasis> gene in Japanese primary breast cancer

Purpose  

The link between BRCA1 dysfunction and basal-like breast cancer or triple-negative breast cancer (TNBC) has been suggested; however, the associations of other factors involved in the Fanconi anemia (FA)/BRCA pathway with the pathogenesis of basal-like breast cancer remain unidentified. FANCF protein is a component of the FA core complex. The methylation of CpG islands in the FANCF gene plays an important role in occurrence of ovarian cancer and also is an important regulator of cisplatin sensitivity of ovarian cancer. The purpose of this study is to investigate the frequency of FANCF methylation, and to discuss its involvement in the pathogenesis of TNBC and its potency as a predictor of cisplatin sensitivity for breast cancer.     

Ovarian cancer risk in Polish <Emphasis Type="Italic">BRCA1</Emphasis> mutation carriers is not associated with the prohibitin 3' untranslated region polymorphism

Background  

The variable penetrance of ovarian cancer in BRCA1 mutation carriers suggests that other genetic or environmental factors modify disease risk. The C to T transition in the 3' untranslated region of the prohibitin (PHB) gene alters mRNA function and has recently been shown to be associated with hereditary breast cancer risk in Polish women harbouring BRCA1 mutations.     

<Emphasis Type="Italic">CDKN1C</Emphasis>/p57<Superscript>kip2</Superscript>is a candidate tumor suppressor gene in human breast cancer

Background  

CDKN1C (also known as p57^KIP2) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21^CIP1 and B/p27^KIP1) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo.     

Mutation analysis of the <Emphasis Type="Italic">MDM4</Emphasis>gene in German breast cancer patients

Background  

MDM4 is a negative regulator of p53 and cooperates with MDM2 in the cellular response to DNA damage. It is unknown, however, whether MDM4 gene alterations play some role in the inherited component of breast cancer susceptibility.     

Breast fibroblasts modulate epithelial cell proliferation in three-dimensional <Emphasis Type="Italic">in vitro</Emphasis> co-culture

Background  

Stromal fibroblasts associated with in situ and invasive breast carcinoma differ phenotypically from fibroblasts associated with normal breast epithelium, and these alterations in carcinoma-associated fibroblasts (CAF) may promote breast carcinogenesis and cancer progression. A better understanding of the changes that occur in fibroblasts during carcinogenesis and their influence on epithelial cell growth and behavior could lead to novel strategies for the prevention and treatment of breast cancer. To this end, the effect of CAF and normal breast-associated fibroblasts (NAF) on the growth of epithelial cells representative of pre-neoplastic breast disease was assessed.     

Lack of evidence for <Emphasis Type="Italic">KRAS</Emphasis> oncogenic mutations in triple-negative breast cancer

Background  

Mutational analysis of the KRAS gene has recently been established as a complementary in vitro diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of KRAS might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although KRAS is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of KRAS in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies.