HER2 Receptor Overexpression Research Articles

Detection of Cervical Lymph Nodes in Head and Neck Cancer: A Study of the Correlation Between Ultrasonic and Histological Findings in Wales

Detection of Cervical Lymph Nodes in Head and Neck Cancer: A Study of the Correlation Between Ultrasonic and Histological Findings in Wales

Biochanin A Modulates Cell Viability, Invasion, and Growth Promoting Signaling Pathways in HER-2-Positive Breast Cancer Cells

Overexpression of HER-2 receptor is associated with poor prognosis and aggressive forms of breast cancer. Scientific literature indicates a preventive role of isoflavones in cancer. Since activation of HER-2 receptor initiates growth-promoting events in cancer cells, we studied the effect of biochanin A (an isoflavone) on associated signaling events like receptor activation, downstream signaling, and invasive pathways. HER-2-positive SK-BR-3 breast cancer cells, MCF-10A normal breast epithelial cells, and NIH-3T3 normal fibroblast cells were treated with biochanin A (2–100 μM) for 72 hours. Subsequently cell viability assay, western blotting and zymography were carried out. The data indicate that biochanin A inhibits cell viability, signaling pathways, and invasive enzyme expression and activity in SK-BR-3 cancer cells. Biochanin A did not inhibit MCF-10A and NIH-3T3 cell viability. Therefore, biochanin A could be a unique natural anticancer agent which can selectively target cancer cells and inhibit multiple signaling pathways in HER-2-positive breast cancer cells.

Predictive and Prognostic Value of Peripheral Blood Cytokeratin-19 mRNA-Positive Cells Detected by Real-Time Polymerase Chain Reaction in Node-Negative Breast Cancer Patients

To evaluate the predictive and prognostic value of peripheral blood cytokeratin-19 (CK-19) mRNA-positive cells in axillary lymph node-negative breast cancer patients. Peripheral blood was obtained from 167 node-negative breast cancer patients before the initiation of any systemic adjuvant therapy, and was analyzed for the presence of CK-19 mRNA-positive cells using a real time polymerase chain reaction assay. The association with known prognostic factors and the effect of CK-19 mRNA-positive cells on patients' prognosis was investigated. CK-19 mRNA-positive cells were detected in the blood of 36 (21.6%) of the 167 patients. There was no correlation between the detection of CK-19 mRNA-positive cells in the peripheral blood and the various known pathologic and clinical prognostic factors; only overexpression of HER2 receptor (score 2+/3+) on the primary tumor was associated with a higher incidence of CK-19 mRNA-positive cell detection (P = .033). Multivariate analysis revealed that detection of peripheral blood CK-19 mRNA-positive cells was associated with early clinical relapse (P < .00001) and disease-related death (P = .008). Detection of peripheral-blood CK-19 mRNA-positive cells is an independent predictive and prognostic factor for reduced disease-free interval and overall survival, respectively, in node-negative breast cancer patients.

Expression of selected markers in patients treated for breast cancer – based on our own data

Summary Background Breast cancer patients’ long-term survival rate depends on many factors, such as the biological features of the tumour, stage of disease and mode of treatment. In most cases, in management of breast cancer combination therapy is used, according to indications. Qualification for adjuvant therapy is based on the assessment of several factors of established prognostic and predictive values. As a standard the patient's age, primary tumour size, axillary lymph node involvement, cancer histological type, its malignancy grade and steroid receptor expression are considered. Aim Analysis of status of selected immunohistochemical markers in a set of consecutive patients undergoing surgery for breast cancer. Materials/Methods Samples from 623 patients were examined. Colour reaction was used for oestrogen (ER) and progesterone (PgR) receptors, P53 protein, cathepsin D and c-erbB-2. Overexpression of HER-2 protein was examined in 150 patients. Results The presence of oestrogen receptors in cell nuclei was detected in 431 (69.2%) patients, of progesterone receptors in 504 (80.2%), and ER+, PgR+ phenotype in 382 (61%) patients. Cathepsin D expression was observed in 438 (70.3%) subjects. In 176 (27.3%) patients P53 protein accumulation was observed. Oncoprotein c-erbB-2 overexpression was observed in 99 (15.9%) and overexpression of HER-2 receptor in 29 (19.8%) patients. Conclusions Nowadays oestrogen receptors are detected more frequently than in patients treated in the years 1980–1986. Detection rates of cathepsin D and P53 protein expression remain at comparable levels. The difference observed in detection rate of c-erbB-2 expression requires further analysis. Assessment of the correlation between expression of studied immunohistochemical markers and survival rate is necessary.

409 POSTER Incidence and implications of HER2 and hormonal receptor overexpression in newly diagnosed metastatic breast cancer

409 POSTER Incidence and implications of HER2 and hormonal receptor overexpression in newly diagnosed metastatic breast cancer

Incidence and implications of HER2 and hormonal receptor overexpression in newly diagnosed metastatic breast cancer (MBC)

764 Background: Overexpression of the HER2 receptor protein predicts a worse prognosis and higher metastatic risk in patients (pts) with breast cancer. HER2 positivity also has a strong predictive value for the clinical benefit of trastuzumab (Herceptin, H). The aim of this study was to assess the incidence of HER2 and ER/PR overexpression in patients with newly diagnosed metastatic breast cancer (MBC) and to compare the characteristics and outcomes of pts with HER2-positive and HER2-negative disease. Methods: From June 2000 to November 2001, 96 centres in France participated in a prospective epidemiological study including 741 consecutive pts with newly diagnosed MBC. HER2 and hormonal receptor overexpression was assessed by immunohistochemistry (IHC). Results: Of the 699 evaluable pts aged 25 to 83 (median 54.6) years, 67% were postmenopausal. Tumour characteristics: 29.6% were HER2 3+ by IHC; 61.4% were ER+, and 66.6% either ER+ or PR+. Notably, 22.4% of ER+ and 21.3% of PR+ tumours were also HER2 IHC ...

Co-expression of steroid and HER2 receptors in breast carcinomas in a large (4,493 cases) population-based Polish study

797 Background: In addition to well-established clinical prognostic and predictive factors (i.e. nodal status), the assessment of parameters such as oestrogen (ER), progesterone (PgR) and HER2 receptor status are needed to make an adequate diagnosis of breast cancer. The study reported here is part of a national HER2 screening project in Poland, which started in 2002 and is still ongoing. By April 2004, 11,557 cases of invasive breast carcinoma had been included. The aim of the study was to investigate the relationship between HER2 and ER/PgR status. Methods: The study was performed in 4,493 non-selected cases of breast cancer. The data originated from 14 oncology centres in Poland and were collected between April 2003 and March 2004. ER, PgR and HER2 receptor status were evaluated by immunohistochemistry (IHC). HER2 IHC results were classed by the DAKO criteria system as: 0, 1+, 2+ or 3+. The cases classed as 0, 1+ and 2+ were considered to have a negative HER2 status. The remaining cases (IHC 3+) were considered HER2 positive. Steroid receptor-positive cases were grouped by the presence of 10% or more positively stained cancer nuclei, regardless of the strength of the stain. A positive ER/PgR status was recorded when ER/PgR receptors were detected. A mixed group consisted of cases in which one steroid hormone was present. Results: The group described by IHC as 0, 1+ and 2+ showed the presence of at least one steroid receptor in more than two-thirds of all cases (71%, 80% and 79%, respectively). Among the tumours exhibiting HER2-receptor overexpression (IHC 3+), 52% were steroid-receptor positive. Conclusion: The results of this large population-based study indicate that there is a relationship between the expression of ER and PgR receptors and HER2 status. The probability of the existence of positive steroid receptor status in the clinically HER2-positive group (3+) was lower than in the clinically HER2-negative group (0, 1+, 2+). However, even so, more than half of the HER2-overexpressing patients were also steroid receptor positive. Taken together, these results emphasise the necessity of independent evaluation of both steroid receptors and HER2 status. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Polska Roche Polska Roche Polska

Alpha-Tocopheryloxybutyric acid enhances necrotic cell death in breast cancer cells treated with chemotherapy agent.

The overexpression of HER-2 receptor contributes to malignant transformation of breast cancer cells. We have reported that alpha-tocopheryloxybutyric acid (TE), non-antioxidative vitamin E ether derivative inhibits the activation of HER-2 receptor. The present study was undertaken to estimate if TE could act as a useful anti-cancer agent against a breast cancer cell overexpressing HER-2 receptor (MDA-MB-453 cell line) in combination with a conventional chemotherapy agent, adriamycin (ADR). TE enhanced cytotoxic effect of ADR against the human breast cancer cell at low doses less than IC(50). The enhancing effect was mainly dependent on the elevation of necrotic-like cell death but not apoptotic cell death. In conjugation with this event, the inactivation of HER-2 receptor in the breast cancer cell was caused by the combination of TE with ADR. These results suggest that TE enhances necrotic-like cell death in the breast cancer cells and that the cell death relates to the inactivation of HER-2 receptor in the breast cancer cells.

Tissue microarray-based studies of patients with lymph node negative breast carcinoma show that met expression is associated with worse outcome but is not correlated with epidermal growth factor family receptors.

It has been shown that receptor tyrosine kinases (RTKs) predict outcome in patients with breast carcinoma. Although RTKs are a large family, HER-2, epidermal growth factor receptor (EGFR), Met (hepatocyte growth factor receptor), and others all have shown the ability to predict outcome. However, it remains unclear whether these markers are defining the same subpopulation of patients with breast carcinoma. In this study, the authors attempted to determine the correlation between RTKs on the basis of their ability to stratify a population according to outcome. The authors used tissue microarray technology to study 324 patients with lymph node negative breast carcinoma who had 20-40 years of follow-up. Expression was assessed using immunohistochemical stains for Met, EFGR, fibroblast growth factor receptor (FGFR), and HER-2. Expression levels were assessed by two observers, and correlations were analyzed. Standard pathology information, including tumor size, nuclear grade, Ki-67 receptor status, and estrogen and progesterone receptor expression levels, also was collected. RTK expression in the study cohort revealed two strong correlations. Specifically, HER-2 and EGFR showed similar expression patterns (P < 0.0001), and Met cytoplasmic domain and FGFR cytoplasmic staining showed similar expression patterns (P < 0.0001), but no correlation was found between the two groups. Of these RTKs, only high levels of Met cytoplasmic domain showed significance as a prognostic marker defining a shortened survival compared with the rest of the population (P = 0.0035; relative risk, 2.04). In the same group of patients, HER-2, hormone receptor status, and other RTK family receptors were not correlated with outcome. In multivariate analysis, only Met cytoplasmic domain and tumor size showed independent predictive value. The current results indicate that the cytoplasmic domain of Met shows a unique staining pattern and defines a set of patients unique from the set of patients defined by overexpression of HER-2, EGFR, or hormone receptors. Furthermore, this group of patients is associated tightly and independently with worse outcome.

TP53 mutation and/or overexpression of the HER2 receptor are strong indicators of poor prognosis in both node-negative and node-positive early breast cancer

TP53 mutation and/or overexpression of the HER2 receptor are strong indicators of poor prognosis in both node-negative and node-positive early breast cancer

Commentary on “HER2/neu as a Predictive Factor in Breast Cancer”

analysis of HER2 receptor overexpression by a panel of 2 monoclonal and 2 polyclonal antibodies indeed demonstrated variability in the ability to predict response to trastuzumab plus paclitaxel.7 This is not surprising, given the potential for less specific polyclonal antibodies to cross-react with antigenic determinants other than HER2.8 An ongoing, prospective, randomized trial among women with metastatic breast cancer (CALGB 9840), among others, should untangle the “immunohistoconfusion” that presently exists. In this trial, tumor specimens are assessed for gene amplification and receptor overexpression with various antibodies, and serum is assayed serially for levels of circulating shed extracellular domain.9 It may well be that a functional assay that detects HER2 in its activated/phosphorylated state may be a more relevant assay10 for predicting response to certain systemic therapies. Methodologic issues aside, what as

The role of overexpressed HER2 in transformation

The HER family of receptors has an important role in the network of cell signals controlling cell growth and differentiation. Although the activity of the HER receptor is strictly controlled in normal cells, HER2 receptor overexpression plays a pivotal role in transformation and tumorigenesis. HER2 gene amplification and/or overexpression of the receptor has been detected in subsets of a wide range of human cancers including breast cancer, and is an indicator of poor prognosis. It is proposed that overexpressed HER2 in combination with HER3 causes high activity of cell-signaling networks, thereby resulting in tumor cell proliferation. Thus, the HER2 receptor is an attractive target for new anti-cancer treatments. Monoclonal antibodies directed against the receptor are the most promising of these, and the humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) has shown significant clinical efficacy in clinical trials. The anti-tumor mechanisms of anti-HER2 monoclonal antibodies are not completely understood. However, some tumor types are not sensitive to trastuzumab, suggesting that the response of a tumor to trastuzumab may not only be dependent on overexpressed HER2, but may also be influenced by other members of the HER receptor family expressed in the tumor cell.