Is expression or activation of Src kinase associated with cancer-specific survival in ER-, PR- and HER2-negative breast cancer patients?

The aim of the current study was to assess the expression levels of c-Src and phosphorylated Src kinase in human breast cancers and to establish if these are linked to oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status or patient survival. Tissue microarray technology was used to analyze 314 breast cancer specimens. Immunohistochemistry was performed using antibodies to c-Src, Y419Src, and Y215Src, and expression was assessed using the weighted histoscore method.

Expression of tumor necrosis factor alpha converting enzyme in endocrine cancers.

Tumor necrosis factor alpha converting enzyme (TACE) mediates shedding of human epidermal growth factor receptor-4 (HER4). Recent data suggest that released HER4 intracellular domain (4ICD) induces apoptosis in breast cancer. TACE expression, as measured by immunohistochemical analysis, was observed in 183 of 383 breast carcinomas, 39 of 217 ovarian carcinomas, and 16 of 24 and 17 of 24 hormonesensitive and hormone-insensitive prostate carcinomas, respectively.

Amplified in breast cancer 1 in human epidermal growth factor receptor - positive tumors of tamoxifen-treated breast cancer patients.

Purpose: Amplified in breast cancer 1 (AIB1) is a member of the p160/steroid receptor coactivators family and is involved in estrogen-dependent gene transcription by reducing the antagonistic activity of tamoxifen-bound estrogen receptor-alpha (ER-alpha). The present study was carried out to test the hypothesis that AIB1 protein expression and/or gene amplification mediates tamoxifen resistance in breast cancer.

Experimental Design: Immunohistochemistry using AIB1 antibody and fluorescence in situ hybridization using probes specific for AIB1 and chromosome 20 was done on 402 ER-alpha-positive tamoxifen-treated breast cancers.

Bad expression predicts outcome in patients treated with tamoxifen.

Aims: Activation of the PI3K/Akt signal transduction pathway has been linked to endocrine resistance in tamoxifen treated breast cancer patients. Activation of the PI3K/Akt pathway causes phosphorylation of Bad leading to modulation of cellular apoptosis. The present study was carried out to test the hypothesis that disruption of apoptosis in breast cancer, via Akt activation, is linked with hormone resistance.

HER4 in breast cancer: comparison of antibodies against intra- and extra-cellular domains of HER4.

Introduction: We have previously linked HER4 expression with increased survival in breast cancer. However, other reports have associated HER4 with adverse prognostic significance. One possible explanation for the conflicting reports may be that these results are antibody dependent.

AKT activation predicts outcome in breast cancer patients treated with tamoxifen.

Oestrogen receptor (ERalpha) expression is a strong predictor of response to endocrine therapy. The PI3K/AKT/mTOR signal transduction pathway has been implicated in endocrine resistance in vitro. The present study was carried out to test the hypothesis that AKT activation mediates tamoxifen resistance in clinical breast cancer.

Outcome and human epidermal growth factor receptor (HER) 1-4 status in invasive breast carcinomas with proliferation indices evaluated by bromodeoxyuridine labelling.

Background: We have shown previously that whereas overexpression of human epidermal growth factor receptor (HER)1, HER2 and HER3 is associated with poor prognosis in breast cancer, HER4 is associated with a good prognosis. Cell proliferation is a key component of aggressive cancers and is driven by growth factors. In this study, bromodeoxyuridine (BrdU)-derived proliferation indices are correlated with clinical outcome and HER1-4 status for further clarification of the differing roles for the HER family at a biological level.