MedWorm: HER2

Lapatinib Plus Letrozole for Postmenopausal Patients With Advanced HER2+/HR+ Breast Cancer

Medscape Hematology-Oncology Headlines — Fri, 19 Mar 2010 13:45:34 +0100

This article reviews the data supporting this chemotherapy option. Expert Review of Anticancer Therapy (Source: Medscape Hematology-Oncology Headlines)

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First-Line Trastuzumab Plus Epirubicin and Cyclophosphamide Therapy in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Cardiac Safety and Efficacy Data From the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) Trial [Breast Cancer]

Journal of Clinical Oncology — Thu, 18 Mar 2010 22:01:36 +0100

Conclusion The HEC regimen is a promising treatment option for patients with HER2-positive MBC. The lower incidence of DLC with HEC, compared with the historic incidence associated with trastuzumab plus doxorubicin, supports further evaluation of the regimen, especially in adjuvant or neoadjuvant settings. (Source: Journal of Clinical Oncology)

Lapatinib plus capecitabine feasible for advanced HER2-positive breast cancer

MedWire News - Breast Cancer — Thu, 18 Mar 2010 00:00:00 +0100

Lapatinib combined with capecitabine is an active treatment option for women with advanced human epidermal growth factor receptor (HER)2-positive breast cancer, including those with progressive central nervous system disease, UK researchers report. (Source: MedWire News - Breast Cancer)

Lapatinib plus capecitabine feasible for advanced HER2-positive breast cancer

MedWire News - Oncology — Thu, 18 Mar 2010 00:00:00 +0100

Ventana Medical Systems Inc - PATHWAY HER2 (4B5) - Class 2 Recall

Medical Device Recalls since July 07, 2006 — Wed, 17 Mar 2010 01:00:05 +0100

VENTANA PATHWAY anti-HER-2/neu (4B5) RABBIT MONOCLONAL PRIMARY ANTIBODY (PATHWAY HER2 (4B5)); Model Number: 790-2991, Lot number: 680957, in vitro diagnostic. (Source: Medical Device Recalls since July 07, 2006)

Drug Combo Found Effective in HER2-Amplified Gastric Cancer

Modern Medicine — Wed, 17 Mar 2010 00:00:00 +0100

Lapatinib (Tykerb) and trastuzumab (Herceptin), two drugs already used in breast cancer treatment, are probably effective when used in combination against upper gastric cancers with the mutation for amplified expression of the human epidermal growth factor receptor 2 protein, according to a study in the March 1 issue of Clinical Cancer Research. (Source: Modern Medicine)

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The β2-adrenergic receptor and Her2 comprise a positive feedback loop in human breast cancer cells

Breast Cancer Research and Treatment — Tue, 16 Mar 2010 14:50:08 +0100

In this study, β2-AR level was found to be up-regulated in MCF-7 cells overexpressing Her2 (MCF-7/Her2). Correlation of β2-AR level with Her2 status was demonstrated in breast cancer tissue samples. Constitutive phosphorylation of ERK, mRNA expression up-regulation of catecholamine-synthesis enzymes, and increased epinephrine release were detected in MCF-7/Her2 cells. β2-AR expression induced by epinephrine and involvement of ERK signaling were validated. The data indicate that Her2 overexpression and excessive phosphorylation of ERK cause epinephrine autocrine release from breast cancer cells, resulting in up-regulation of β2-AR expression. The data also showed that catecholamine prominently stimulated Her2 mRNA expression and promoter activity. The activation and nuclear transl...

The Rebirth of a Phoenix: Ovarian Cancers Are Addicted to ErbB-3

Cancer Cell — Tue, 16 Mar 2010 04:00:10 +0100

Gordon B. Mills, Yosef Yarden. Several cancer drugs intercept the ErbB family receptors EGFR (ErbB-1) and HER2 (ErbB-2). However, the therapeutic value of targeting ErbB-3 has been less clear. A report in this issue of Cance.... (Source: Cancer Cell)

Variables with time-varying effects and the Cox model: Some statistical concepts illustrated with a prognostic factor study in breast cancer

BMC Medical Research Methodology - Latest articles — Tue, 16 Mar 2010 00:00:00 +0100

Conclusions: Investigating time-varying effects should be an integral part of Cox survival analyses. Detecting and accounting for time-varying effects provide insights on some specific time patterns, and on valuable biological information that could be missed otherwise. (Source: BMC Medical Research Methodology - Latest articles)

Downregulation of Notch Pathway by a {gamma}-Secretase Inhibitor Attenuates AKT/Mammalian Target of Rapamycin Signaling and Glucose Uptake in an ERBB2 Transgenic Breast Cancer Model

Cancer Research — Mon, 15 Mar 2010 04:07:29 +0100

Gamma secretase inhibitors developed initially for Alzheimer's disease might provide therapeutic benefit to a subset of HER2 breast cancers. (Source: Cancer Research)

Disruption of Laminin-Integrin-CD151-Focal Adhesion Kinase Axis Sensitizes Breast Cancer Cells to ErbB2 Antagonists

Cancer Research — Mon, 15 Mar 2010 04:07:28 +0100

An integrin pathway-mediated mechanism of drug resistance to HER2 disrupting agents is described. (Source: Cancer Research)

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GP96 C-terminal improves Her2/neu DNA vaccine

The Journal of Gene Medicine — Mon, 15 Mar 2010 00:00:00 +0100

DNA vaccines ensure protective immunity against tumors in a variety of experimental models. The favorite target tumor-associated antigens have been those that are frequently expressed by human tumors, such as Her2. However, the efficacy of active vaccination is limited because Her2 is a self-tolerated antigen. Many strategies have been applied to increase the efficacy of DNA vaccination, such as fusion or co-administration of Her2 with cytokine and co-stimulatory molecules. GP96 is involved in innate and adaptive immune responses and evokes potent activation and maturation of dendritic cells along with increased secretion of pro-inflammatory cytokines. On the basis of previous studies, we expected the C-terminal of GP96 to act as a package and as a suitable substitute for both cytokine and...

Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy

Breast Cancer Research and Treatment — Sun, 14 Mar 2010 11:26:10 +0100

Abstract The Forkhead Box Protein 3 is highly expressed not only in regulatory T cells, but also in tumor cells, acting as a transcriptional repressor of breast oncogenes including HER2. We investigated the prognostic significance of Foxp3 expression in cancer cells in a large cohort of patients with HER2-overexpressing breast carcinoma treated with neoadjuvant chemotherapy. Foxp3-positive tumor cells were detected by immunohistochemistry in 103 patients with primary invasive HER2-overexpressing breast carcinoma, and treated with neoadjuvant chemotherapy, with or without trastuzumab. Kaplan–Meier analysis and Cox regression model were used to assess relapse-free and overall survival, respectively, and according to the presence or the absence of Foxp3 expression in tumor c...

Efficacy of ixabepilone in ER/PR/HER2-negative (triple-negative) breast cancer

Breast Cancer Research and Treatment — Sun, 14 Mar 2010 11:26:10 +0100

Abstract Patients with ER/PR/HER2-negative (triple negative) breast cancer are not candidates for hormonal therapy or HER2-targeted agents. Ongoing research is aimed at identifying and understanding the benefit of established and emerging therapies in this disease setting. Triple-negative patients may achieve early responses to anthracyclines and taxanes, but novel strategies are also eagerly sought. The epothilone B analog ixabepilone acts to stabilize microtubules and demonstrates antitumor activity in recent breast cancer studies. Herein, we have analyzed efficacy and safety data of ixabepilone specifically for the treatment of women with triple-negative disease. A retrospective analysis was completed using activity and toxicity data in the triple-negative subsets from ...

Potential prognostic value of heat shock protein 90 in the presence of phosphatidylinositol-3-kinase overexpression or loss of PTEN, in invasive breast cancers

Breast Cancer Research — Fri, 12 Mar 2010 00:00:00 +0100

Conclusions: The co-expression of HSP90 with PI3K-p110alpha or expression of HSP90 along with PTEN loss have potential as molecular prognostic markers to predict early relapse in patients with invasive breast cancers. (Source: Breast Cancer Research)

N-terminally fusion of Her2/neu to HSP70 decreases efficiency of Her2/neu DNA vaccine.

Cell Stress and Chaperones — Fri, 12 Mar 2010 00:00:00 +0100

In this study, we examined if N-terminally fusion of Her2/neu to HSP70 could also improve efficiency of Her2/neu DNA vaccine. Therefore, mice with an established Her2/neu expressing tumor were immunized with DNA vaccine consisting of extracellular and trans-membrane domain (EC+TM) of rat Her2/neu alone or N-terminally fused to HSP70 and immune response was evaluated. Administration of rat Her2/neu led to partial control of tumor progression. Surprisingly, fusion of HSP70 to N-terminal of rat Her2/neu led to tumor progression. Our result proposes that fusion direction of biologic adjuvant is an important consideration when Her2/neu is used. PMID: 20224916 [PubMed - as supplied by publisher] (Source: Cell Stress and Chaperones)

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In Situ Identification of Putative Cancer Stem Cells by Multiplexing ALDH1, CD44, and Cytokeratin Identifies Breast Cancer Patients with Poor Prognosis.

The American Journal of Pathology — Fri, 12 Mar 2010 00:00:00 +0100

Authors: Neumeister V, Agarwal S, Bordeaux J, Camp RL, Rimm DL A subset of cells, tentatively called cancer stem cells (CSCs), in breast cancer have been associated with tumor initiation, drug resistance, and tumor persistence or aggressiveness. They are characterized by CD44 positivity, CD24 negativity, and/or ALDH1 positivity in flow cytometric studies. We hypothesized that the frequency or density of these cells may be associated with more aggressive tumor behavior. We borrowed these multiplexed, flow-based methods to develop an in situ method to define CSCs in formalin-fixed paraffin-embedded breast cancer tissue, with the goal of assessing the prognostic value of the presence of CSCs in breast cancer. Using a retrospective collection of 321 node-negative and 318 node-positive pati...

Gene silencing by cell-penetrating, sequence-selective and nucleic-acid hydrolyzing antibodies

Nucleic Acids Research — Thu, 11 Mar 2010 08:57:24 +0100

Targeting particular mRNAs for degradation is a fascinating approach to achieve gene silencing. Here we describe a new gene silencing tool exploiting a cell-penetrating, nucleic-acid hydrolyzing, single-domain antibody of the light-chain variable domain, 3D8 VL. We generated a synthetic library of 3D8 VL on the yeast surface by randomizing residues located in one of two β-sheets. Using 18-bp single-stranded nucleic acids as target substrates, including the human Her2/neu-targeting sequence, we selected 3D8 VL variants that had ~100–1000-fold higher affinity and ~2–5-fold greater selective hydrolyzing activity for target substrates than for off targets. 3D8 VL variants efficiently penetrated into living cells to be accumulated in the cytosol and selectively decreased the am...

Combined detection of Her2/neu gene amplification and protein overexpression in effusions from patients with breast and ovarian cancer

Journal of Cancer Research and Clinical Oncology — Wed, 10 Mar 2010 16:10:22 +0100

Conclusion The combination of IHC and FISH allows a differentiated analysis of single cells, which is especially important for effusions that are composed of heterogeneous cells. Therefore, cells with high gene amplification and/or protein overexpression can be detected and analysed even if their amount in the sample is small. Chromosome 17 polyploidy is important in some cases but this should be further examined on a larger series. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00432-010-0790-2Authors Birgitta Schlüter, Klinikum der Ruhr-Universität Bochum Marienhospital Herne, Medizinische Klinik III: Hämatologie und Onkologie Hölkeskampring 40 44625 Herne GermanyRoswitha Gerhards, Klinikum der Ruhr-Universität Bochum Marienhospital Herne, M...

Comparison of microarray-based RNA expression with ELISA-based protein determination of HER2, uPA and PAI-1 in tumour tissue of patients with breast cancer and relation to outcome

Journal of Cancer Research and Clinical Oncology — Wed, 10 Mar 2010 16:10:10 +0100

Conclusions Results of RNA-based multi-gene analyses of the prognostic and predictive markers HER2 and uPA correlate with the corresponding protein levels. This is not the case for PAI-1. However, PAI-1 mRNA expression might reveal new clinically relevant information in addition to PAI protein levels. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00432-010-0829-4Authors Isabell D. Witzel, University Medical Center Hamburg-Eppendorf Department of Gynecology Martinistrasse 52 20246 Hamburg GermanyKarin Milde-Langosch, University Medical Center Hamburg-Eppendorf Department of Gynecology Martinistrasse 52 20246 Hamburg GermanyRalph M. Wirtz, Siemens Healthcare Diagnostics Products GmbH Cologne GermanyClaudia Roth, Siemens Healthcare Diagnostics Product...

Topoisomerase 2 Alpha and the Case for Individualized Breast Cancer Therapy

Annals of Surgical Oncology — Wed, 10 Mar 2010 16:00:56 +0100

Conclusions It seems increasingly likely that response to anthracyclines is predicated on these alterations. Content Type Journal ArticleCategory Breast OncologyDOI 10.1245/s10434-009-0855-0Authors Ronan W. Glynn, National University of Ireland, Galway, Clinical Science Institute Department of Surgery Costello Road Galway IrelandNicola Miller, National University of Ireland, Galway, Clinical Science Institute Department of Surgery Costello Road Galway IrelandMaria C. Whelan, National University of Ireland, Galway, Clinical Science Institute Department of Surgery Costello Road Galway IrelandMichael J. Kerin, National University of Ireland, Galway, Clinical Science Institute Department of Surgery Costello Road Galway Ireland Journal Annals of Surgical OncologyOnlin...

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Does Analysis of Biomarkers in Tumor Cells in Lymph Node Metastases Give Additional Prognostic Information in Primary Breast Cancer?

World Journal of Surgery — Wed, 10 Mar 2010 15:57:20 +0100

Conclusions The concordance for the biomarkers analyzed in matched pairs of primary tumors and lymph node metastases was high. Moreover, survival analyses showed that the expression of biomarkers in lymph node metastases can provide prognostic information when no analyses of the primary tumor can be done. Treatment selection based on biomarkers in the lymph node is a topic for further studies. Content Type Journal ArticleDOI 10.1007/s00268-010-0499-zAuthors Anna-Karin Falck, Lund University Hospital Department of Surgery, Institution of Clinical Sciences Lund SE-221 85 Lund SwedenMårten Fernö, Lund University Hospital Department of Oncology, Institution of Clinical Sciences Lund SE-221 85 Lund SwedenPär-Ola Bendahl, Lund University Hospital Department of Oncolog...

Osthole Suppresses Fatty Acid Synthase Expression in HER2-Overexpressing Breast Cancer Cells through Modulating Akt/mTOR Pathway

Journal of Agricultural and Food Chemistry — Wed, 10 Mar 2010 14:12:33 +0100

Journal of Agricultural and Food Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Agricultural and Food Chemistry)

Immunoconjugated gold nanoshell-mediated photothermal ablation of trastuzumab-resistant breast cancer cells

Breast Cancer Research and Treatment — Wed, 10 Mar 2010 13:17:33 +0100

Abstract Trastuzumab is a FDA-approved drug that has shown clinical efficacy against HER2+ breast cancers and is commonly used in combination with other chemotherapeutics. However, many patients are innately resistant to trastuzumab, or will develop resistance during treatment. Alternative treatments are needed for trastuzumab-resistant patients. Here, we investigate gold nanoparticle-mediated photothermal therapies as a potential alternative treatment for chemotherapy-resistant cancers. Gold nanoshell photothermal therapy destroys the tumor cells using heat, a physical mechanism, which is able to overcome the cellular adaptations that bestow trastuzumab resistance. By adding anti-HER2 to the gold surface of the nanoshells as a targeting modality, we increase the specifici...

HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic value - conclusions from 924 cases of two independent series.

Cellular Oncology — Wed, 10 Mar 2010 13:06:02 +0100

Conclusions: This is the largest study to date demonstrating in two independent series that HER2 expression is not related to gastric cancer patient prognosis and that only a very small subgroup of intestinal type GC may potentially respond to HER2 targeting therapy. Due to prominent intratumoural heterogeneity of HER2 expression in GC, HER2 testing in endoscopic biopsies before treatment will be prone to false negative results. PMID: 20208134 [PubMed - in process] (Source: Cellular Oncology)

Randomized Phase II Multicenter Trial of Two Schedules of Lapatinib as First- or Second-Line Monotherapy in Patients with Advanced or Metastatic Non-Small Cell Lung Cancer.

Clinical Cancer Research — Tue, 09 Mar 2010 00:00:00 +0100

CONCLUSIONS: Lapatinib was well tolerated, with no notable difference in toxicity between treatment groups. Lapatinib monotherapy did not induce a significant number of tumor regressions in NSCLC. Further studies may be warranted to determine whether lapatinib is active in combination with other agents in the treatment of NSCLC. Clin Cancer Res; 16(6); 1938-49. PMID: 20215545 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

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Dynamic Breast MRI in the Course of Neoadjuvant Chemotherapy: Standardized Evaluation of Tumor Size and Enhancement Parameters in Correlation to Different Histopathologic Characteristics

Academic Radiology — Mon, 08 Mar 2010 15:54:33 +0100

Conclusions: From routine MRI protocol and semiquantitative analysis of signal enhancement curves, information about size, and hemodynamic status of tumors under treatment may be extracted. Reduction in size and maximum enhancement were complementary parameters. In the course of therapy, size and enhancement may develop differently in clinically relevant histopathological subgroups. (Source: Academic Radiology)

Weekly paclitaxel plus carboplatin is an effective nonanthracycline-containing regimen as neoadjuvant chemotherapy for breast cancer.

Ann Oncol — Mon, 08 Mar 2010 00:00:00 +0100

CONCLUSIONS: Weekly PCb regimen was very active and tolerable as neoadjuvant treatment of breast cancer. This weekly PCb regimen should consider as a reasonable nonanthracycline-containing option in the neoadjuvant treatment of breast cancer. PMID: 20211870 [PubMed - as supplied by publisher] (Source: Ann Oncol)

Classification of HER2 Receptor Status in Breast Cancer Tissues by MALDI Imaging Mass Spectrometry

Journal of Proteome Research — Fri, 05 Mar 2010 17:57:23 +0100

Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Proteome Research)

Potent inhibition of human gastric cancer by HER2-directed induction of apoptosis with anti-HER2 antibody and caspase-3 fusion protein

Gut — Fri, 05 Mar 2010 11:12:51 +0100

Conclusions The HER-PE-CP3 chimeric molecule could induce selective apoptosis and potent growth inhibition of HER2-positive human gastric cancer cells and might represent a novel HER2-directed treatment option for human gastric cancer. (Source: Gut)

Out of the darkness and into the light: bright field in situ hybridisation for delineation of ERBB2 (HER2) status in breast carcinoma

Journal of Clinical Pathology — Thu, 04 Mar 2010 15:42:49 +0100

Assessment of ERBB2 (HER2) status in breast carcinomas has become critical in determining response to the humanised monoclonal antibody trastuzumab. The current joint College of American Pathologists and the American Society of Clinical Oncology guidelines for the evaluation of HER2 status in breast carcinoma involve testing by immunohistochemistry and fluorescence in situ hybridisation (FISH). However, neither of these modalities is without limitations. Novel bright field in situ hybridisation techniques continue to provide viable alternatives to FISH testing. While these techniques are not limited to evaluation of the HER2 gene, the extensive number of studies comparing bright field in situ techniques with other methods of assessing HER2 status allow a robust evaluation of this approach....

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The clinicopathological characteristics of 'triple-negative' epithelial ovarian cancer

Journal of Clinical Pathology — Thu, 04 Mar 2010 15:42:49 +0100

Conclusions A novel subtype of ovarian carcinoma, which is negative for ER, PR and HER2 expression, has been identified; this specific ovarian subtype tends to have aggressive characteristics and a poor prognosis, which is similar to triple-negative breast cancer in most respects. TNEOC should be considered in future investigations of informative classification of ovarian cancer. (Source: Journal of Clinical Pathology)

Imaging and biodistribution of Her2/neu expression in non-small cell lung cancer xenografts with 64Cu-labeled trastuzumab PET

Cancer Science — Thu, 04 Mar 2010 00:00:00 +0100

Non-small cell lung carcinomas (NSCLC) overexpress the Her2/neu gene in approximately 59% of cases. Trastuzumab, a humanized monoclonal antibody, interferes with Her2 signaling and is approved for the treatment of Her2/neu overexpressing breast cancer. However, its therapeutic use in Her2/neu overexpressing NSCLC remains obscure. The present study aimed to determine the role of 64Cu-labeled trastuzumab positron emission tomography (PET) for non-invasive imaging of Her2/neu expression in NSCLC. Trastuzumab was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with 64Cu. The molecular specificity of DOTA-trastuzumab was determined in NSCLC cell lines with Her2/neu overexpression (NCI-H2170) and negative expression...

Herceptin And Tykerb Effective Against A Subset Of Gastric Cancers

Health News from Medical News Today — Wed, 03 Mar 2010 14:00:00 +0100

A combination of two targeted therapies already shown to be effective in breast cancer packs an effective one-two punch against a subset of gastric cancers that have a specific genetic mutation, a study at UCLA's Jonsson Comprehensive Cancer Center has found. The drugs Herceptin and Tykerb when given together proved to significantly inhibit tumor growth in gastric cancers that had amplified levels of HER2, a mutation that results in an aggressive form of the disease, causing the cancers to grow and spread faster... (Source: Health News from Medical News Today)

Should adjuvant trastuzumab be offered in very early-stage (pT1a/bN0M0) HER2-neu-positive breast cancer? A current debate

Medical Oncology — Tue, 02 Mar 2010 10:07:46 +0100

Abstract There are many controversies regarding the treatment of very early-stage (pT1a/bN0M0) breast cancer (BC), generally considered to have a very good prognosis. The debate is the benefit of an adjuvant treatment of HER2-neu (namely HER-2)-positive subcentimetric carcinoma with trastuzumab. Current guidelines do not suggest, with the highest level of evidence, whether trastuzumab should be administered after adjuvant chemotherapy in the treatment of high-risk pT1a/bN0M0 breast cancer. The major phase III trials that confirmed the benefit of adjuvant immunotherapy did not include small (<1 cm diameter) node-negative breast cancer. Several retrospective case series of HER-2-positive pT1a/bN0M0 carcinoma seem to demonstrate that they have a higher risk of relapse ...

Can genes predict drug response?

NHS News Feed — Mon, 01 Mar 2010 11:32:00 +0100

Conclusion Identifying ways to tailor treatment based on an individual’s genetic makeup is a growing area of research, aiming to increase the likelihood of a treatment response while reducing the risk of adverse effects. This study has identified a panel of genes whose activity could help to predict those women with triple negative breast cancers who will respond to paclitaxel treatment before surgery. These findings will need to be replicated in other groups of women, particularly as there was only a small number of paclitaxel-treated women with triple negative breast cancers in this study. Such research will be needed to confirm how many false positives (proportion of women that the test predicts will respond to treatment that do not) and false negatives (proportion of women that the t...

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[Leading Edge] New hope for advanced gastric cancer

The Lancet Oncology — Mon, 01 Mar 2010 00:00:00 +0100

On Jan 28, 2010, European authorities approved trastuzumab—a monoclonal antibody against HER2—in combination with chemotherapy for first-line treatment of patients with HER2-positive advanced gastric cancer. The licence was granted following the positive opinion of the Committee for Medicinal Products for Human Use, and was reviewed through an accelerated process after promising findings were reported from the international phase 3 ToGA (Trastuzumab for Gastric Cancer) trial comparing trastuzumab in combination with standard chemotherapy versus standard chemotherapy alone for the treatment of HER2-positive advanced gastric cancer. This is the first targeted biological therapy to show a survival benefit in this difficult-to-treat cancer and, with several targeted agents currently being ...

[Reflection and Reaction] Doubling back on centromere 17 in early breast cancer

The Lancet Oncology — Mon, 01 Mar 2010 00:00:00 +0100

Anthracycline chemotherapy produces a modest improvement in survival for women with early-stage breast cancer. However, these drugs are associated with serious long-term side-effects—eg, secondary congestive heart failure and leukaemia—and careful selection is needed to ensure that anthracyclines are given only to patients who may benefit from them. A meta-analysis of eight randomised trials concluded that the benefit of anthracyclines was limited to patients with HER2 amplification. However, not all studies are consistent and a clear mechanistic link between HER2 amplification and anthracycline sensitivity remains elusive. TOP2A, which neighbours HER2 on chromosome 17 (Ch17), is frequently co-amplified in HER2-positive tumours and encodes a TOP2A DNA replication protein that is inhibi...

[Reflection and Reaction] HER2 as a cancer stem-cell target

The Lancet Oncology — Mon, 01 Mar 2010 00:00:00 +0100

The recent review by Jones and Buzdar comprehensively examines the role of the human epidermal growth-factor receptor-2 (HER2) in breast cancer initiation and progression, and the role of agents targeting HER2 (trastuzumab, lapatinib, and others) in the treatment of breast cancer. However, the authors did not mention recent evidence that HER2-mediated carcinogenesis and tumorigenesis might be due to the protein's action on tumour-initiating cells or cancer stem cells in HER2-positive breast cancers, and that the clinical efficacy of trastuzumab might be related to the drug's ability to target cancer stem cells. (Source: The Lancet Oncology)

[Articles] Predictive markers of anthracycline benefit: a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (NEAT/BR9601)

The Lancet Oncology — Mon, 01 Mar 2010 00:00:00 +0100

The NEAT/BR9601 trial showed benefit for addition of anthracyclines to cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant treatment for early breast cancer. We investigated prospectively predictive biomarkers of anthracycline benefit including HER2 and TOP2A. (Source: The Lancet Oncology)

Ethanol Enhances the Interaction of Breast Cancer Cells Over-Expressing ErbB2 With Fibronectin

Alcoholism: Clinical and Experimental Research — Mon, 01 Mar 2010 00:00:00 +0100

Conclusions: Our results suggest that ethanol enhances the adhesion of breast cancer cells to fibronectin in an ErbB2-dependent manner, and the FAK pathway plays an important role in ethanol-induced formation of a focal complex. (Source: Alcoholism: Clinical and Experimental Research)

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Computerized Image-Based Detection and Grading of Lymphocytic Infiltration in HER2+ Breast Cancer Histopathology

IEEE Transactions on Biomedical Engineering — Mon, 01 Mar 2010 00:00:00 +0100

The identification of phenotypic changes in breast cancer (BC) histopathology on account of corresponding molecular changes is of significant clinical importance in predicting disease outcome. One such example is the presence of lymphocytic infiltration (LI) in histopathology, which has been correlated with nodal metastasis and distant recurrence in HER2+ BC patients. In this paper, we present a computer-aided diagnosis (CADx) scheme to automatically detect and grade the extent of LI in digitized HER2+ BC histopathology. Lymphocytes are first automatically detected by a combination of region growing and Markov random field algorithms. Using the centers of individual detected lymphocytes as vertices, three graphs (Voronoi diagram, Delaunay triangulation, and minimum spanning tree) are const...

Ethanol Enhances the Interaction of Breast Cancer Cells Over-Expressing ErbB2 With Fibronectin.

Alcoholism, Clinical and Experimental Research — Mon, 01 Mar 2010 00:00:00 +0100

Conclusions: Our results suggest that ethanol enhances the adhesion of breast cancer cells to fibronectin in an ErbB2-dependent manner, and the FAK pathway plays an important role in ethanol-induced formation of a focal complex. PMID: 20201928 [PubMed - as supplied by publisher] (Source: Alcoholism, Clinical and Experimental Research)

Drug Combo Approved for Advanced Breast Ca

Ob.Gyn. News — Mon, 01 Mar 2010 00:00:00 +0100

The Food and Drug Administration has approved lapatinib in combination with letrozole for the treatment of postmenopausal women with advanced breast cancer that is hormone receptor and HER2 positive and for whom hormonal therapy is indicated. (Source: Ob.Gyn. News)

Drug Combo Approved for Advanced Breast Ca

Clinical Endocrinology News — Mon, 01 Mar 2010 00:00:00 +0100

Her4 and Her2/neu Tyrosine Kinase Domains Dimerize and Activate in a Reconstituted in Vitro System [Signal Transduction]

Journal of Biological Chemistry — Fri, 26 Feb 2010 14:42:01 +0100

Her4 (ErbB-4) and Her2/neu (ErbB-2) are receptor-tyrosine kinases belonging to the epidermal growth factor receptor (EGFR) family. Crystal structures of EGFR and Her4 kinase domains demonstrate kinase dimerization and activation through an allosteric mechanism. The kinase domains form an asymmetric dimer, where the C-lobe surface of one monomer contacts the N-lobe of the other monomer. EGFR kinase dimerization and activation in vitro was previously reported using a nickel-chelating lipid-liposome system, and we now apply this system to all other members of the EGFR family. Polyhistidine-tagged Her4, Her2/neu, and Her3 kinase domains are bound to these nickel-liposomes and are brought to high local concentration, mimicking what happens to full-length receptors in vivo following ligand bindi...

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Is there a clear role for hormonal therapy in metastatic breast cancer?

Cancer Network — Fri, 26 Feb 2010 12:00:00 +0100

Nationally recognized breast cancer specialist Eric P. Winer, MD, presented two lectures at this year’s MBCC, “Strategies for Patients with Refractory HER2-Positive Breast Cancer,” and “Addressing Menopausal Symptoms and Fertility in Breast Cancer.” In an exclusive interview with ONCOLOGY, Dr. Winer explained how hormonal therapy can best be used in the difficult stetting of metastatic disease. (Source: Cancer Network)

Serum HER-2 concentration is associated with insulin resistance and decreases after weight loss

Nutrition & Metabolism — Thu, 25 Feb 2010 00:00:00 +0100

Conclusions: Serum HER-2 concentrations might be implicated in the pathophysiology of insulin resistance and associated comorbidities. (Source: Nutrition & Metabolism)

Targeted HER2 Treatment in Advanced Gastric Cancer.

Oncology — Thu, 25 Feb 2010 00:00:00 +0100

Authors: Jørgensen JT Amplification of the HER2 gene and over-expression of the HER2 protein in gastric cancer have been shown in a large number of studies. HER2 positivity can be detected in approximately 20% of patients, which is a characteristic associated with poor prognosis. Preclinical in vitro and in vivo studies have demonstrated that both trastuzumab and lapatinib are effective in different gastric cancer models and have thus lead to the initiation of clinical studies. In the first phase III study, the ToGA trial, HER2-positive patients with advanced gastroesophageal and gastric adenocarcinoma were randomized to receive 5-fluorouracil/capecitabine and cisplatin either alone or in combination with trastuzumab. A statically significant gain in overall survival was seen in t...

Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer [Gynecologic Cancer]

Journal of Clinical Oncology — Wed, 24 Feb 2010 23:01:03 +0100

Conclusion Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. Low HER3 mRNA expression may predict pertuzumab clinical benefit and be a valuable prognostic marker. (Source: Journal of Clinical Oncology)

Whither HER2-Related Therapeutics? [EDITORIALS]

Journal of Clinical Oncology — Wed, 24 Feb 2010 23:01:02 +0100

(Source: Journal of Clinical Oncology)

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Open-Label, Phase II, Multicenter, Randomized Study of the Efficacy and Safety of Two Dose Levels of Pertuzumab, a Human Epidermal Growth Factor Receptor 2 Dimerization Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer [Breast Cancer]

Journal of Clinical Oncology — Wed, 24 Feb 2010 23:01:02 +0100

Conclusion The limited efficacy observed in this study, generally SD of relatively short duration, suggested little benefit of further investigation of single-agent pertuzumab in unselected patients with HER2-negative disease. (Source: Journal of Clinical Oncology)

Phase II Trial of Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer That Progressed During Prior Trastuzumab Therapy [Breast Cancer]

Journal of Clinical Oncology — Wed, 24 Feb 2010 23:01:02 +0100

Conclusion The combination of pertuzumab and trastuzumab is active and well tolerated in patients with metastatic HER2-positive breast cancer who had experienced progression during prior trastuzumab therapy. (Source: Journal of Clinical Oncology)

Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer [Breast Cancer]

Journal of Clinical Oncology — Wed, 24 Feb 2010 23:01:02 +0100

Conclusion Single-agent cisplatin induced response in a subset of patients with TNBC. Decreased BRCA1 expression may identify subsets of TNBCs that are cisplatin sensitive. Other biomarkers show promise in predicting cisplatin response. (Source: Journal of Clinical Oncology)

Real-Time RT-PCR Analysis for Evaluating the Her2/neu Status in Breast Cancer

Karger Publishers — Wed, 24 Feb 2010 23:00:00 +0100

Pathobiology 2010;77:3845 (DOI:10.1159/000272953) (Source: Karger Publishers)

Pleomorphic phenotypes of gastrointestinal stromal tumors at metastatic sites with or without imatinib treatment

Cancer Science — Wed, 24 Feb 2010 00:00:00 +0100

In this study, we analyzed the genotypes and the histologic and immunohistochemical phenotypes of metastatic GISTs with and without imatinib treatment, and clarified the pleomorphic nature of metastatic GISTs. We examined 31 autopsy cases in which the patients died of multiple metastases of GISTs, and two surgically resected specimens with and without imatinib treatment. A total of 152 primary and metastatic lesions in 33 cases of GISTs were examined for histologic and immunohistochemical expression of KIT and CD34. We analyzed the expression of other receptor tyrosine kinases (RTKs) in KIT-negative lesions, including human EGFR-related 2 (HER2), epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (MET), platelet-derived growth factor receptor-[alpha] (PDGFRA), and p...

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Alterations in p53, BRCA1, ATM, PIK3CA, and HER2 genes and their effect in modifying clinicopathological characteristics and overall survival of Bulgarian patients with breast cancer

Journal of Cancer Research and Clinical Oncology — Tue, 23 Feb 2010 07:20:33 +0100

Conclusions Our data indicated that p53, BRCA1, ATM, PIK3CA, and HER2 alterations specifically correlate with clinicopathological characteristics of Bulgarian patients with breast cancer. Of these genes, only mutated p53 showed significant, though not independent, negative effect on overall survival. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00432-010-0824-9Authors Stefan S. Bozhanov, Bulgarian Academy of Sciences Institute of Genetics “Akad. Doncho Kostoff”, Department of Molecular Genetics “Plovdivsko shosse” 13 km. 1113 Sofia BulgariaSvetla G. Angelova, Bulgarian Academy of Sciences Institute of Genetics “Akad. Doncho Kostoff”, Department of Molecular Genetics “Plovdivsko shosse” 13 km. 1113 Sofia BulgariaMaria E. Krasteva, ...

Differential survival following trastuzumab treatment based on quantitative HER2 expression and HER2 homodimers in a clinic-based cohort of patients with metastatic breast cancer

BMC Cancer — Tue, 23 Feb 2010 00:00:00 +0100

Conclusions: These data suggest that the quantitative amount of HER2 expression measured by Hermark may be a new useful marker to identify a more relevant target population for trastuzumab treatment in patients with MBC. (Source: BMC Cancer)

[Management of metastatic HER2-positive breast cancer: present and future.]

Bulletin du Cancer — Tue, 23 Feb 2010 00:00:00 +0100

Authors: Guiu S, Coudert B, Favier L, Arnould L, Fumoleau P HER2-positive breast cancer accounts for 20 to 25% of breast cancers. The surexpression of this tyrosine-kinase receptor is often associated with a poor prognosis. However, the management and the outcome of these patients have changed these last ten years with trastuzumab. Despite the encouraging results obtained with this humanized monoclonal antibody directed against the HER2-receptor, used alone or in association with chemotherapy in metastatic patients, progression under trastuzumab are usually observed and resistances to this treatment are described. Thus, many other monoclonal antibodies and tyrosine-kinase inhibitors emerged. These therapeutics, used alone or in association with chemotherapy or trastuzumab have variable...

Low Level Her2 Overexpression Is Associated with Rapid Tumor Cell Proliferation and Poor Prognosis in Prostate Cancer.

Clinical Prostate Cancer — Tue, 23 Feb 2010 00:00:00 +0100

CONCLUSIONS: Low-level Her2 overexpression occurs at relevant frequency in prostate cancer and in the absence of gene amplification. Increased Her2 expression may potentially lead to an aggressive behavior of tumor cells through the stimulation of tumor cell proliferation because Her2 staining was shown to be significantly associated with Ki67 labeling index. These data argue for reconsidering anti-Her2 therapy, possibly with modified approaches. Clin Cancer Res; 16(5); 1553-60. PMID: 20179235 [PubMed - as supplied by publisher] (Source: Clinical Prostate Cancer)

Does Lapatinib Work against HER2-negative Breast Cancers?

Clinical Breast Cancer — Tue, 23 Feb 2010 00:00:00 +0100

Authors: Mayer IA, Arteaga CL Aberrant growth factor receptor signaling can augment or suppress estrogen receptor (ER) function in hormone-dependent breast cancer cells and lead to escape from anti-estrogen therapy. Interruption of HER2/ER cross-talk with lapatinib can restore sensitivity to anti-estrogens and thus, should be investigated in combination with endocrine therapy in patients with ER+/HER2-negative breast cancers. Clin Cancer Res; 16(5); 1355-7. PMID: 20179241 [PubMed - as supplied by publisher] (Source: Clinical Breast Cancer)

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An Adenoviral Vaccine Encoding Full-Length Inactivated Human Her2 Exhibits Potent Immunogenicty and Enhanced Therapeutic Efficacy without Oncogenicity.

Clinical Breast Cancer — Tue, 23 Feb 2010 00:00:00 +0100

CONCLUSIONS: Vaccination with mutationally inactivated, nononcogenic Ad-HER2-ki results in robust polyclonal immune responses to HER2 in tolerant models, which translates into strong and effective antitumor responses in vivo. Ad-HER2-ki is thus a safe and promising vaccine for evaluation in clinical trials. Clin Cancer Res; 16(5); 1466-77. PMID: 20179231 [PubMed - as supplied by publisher] (Source: Clinical Breast Cancer)

Cyclooxygenase-2 Inhibition Does Not Improve the Reduction in Ductal Carcinoma In situ Proliferation with Aromatase Inhibitor Therapy: Results of the ERISAC Randomized Placebo-Controlled Trial.

Clinical Breast Cancer — Tue, 23 Feb 2010 00:00:00 +0100

CONCLUSIONS: Exemestane reduces proliferation in ER-positive DCIS. Aromatase inhibition is a potential alternative to tamoxifen in patients who have undergone breast conservation for ER-positive DCIS. Clin Cancer Res; 16(5); 1605-12. PMID: 20179229 [PubMed - as supplied by publisher] (Source: Clinical Breast Cancer)

Lapatinib Restores Hormone Sensitivity with Differential Effects on Estrogen Receptor Signaling in Cell Models of Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer with Acquired Endocrine Resistance.

Clinical Breast Cancer — Tue, 23 Feb 2010 00:00:00 +0100

CONCLUSIONS: Aberrant GFR signaling can augment or suppress ERalpha function. Regardless, interrupting the HER2/ERalpha cross-talk with lapatinib can restore endocrine sensitivity and should be investigated as a therapeutic strategy in combination with endocrine therapy in ERalpha+/HER2- patients with acquired endocrine resistance. Clin Cancer Res; 16(5); 1486-97. PMID: 20179226 [PubMed - as supplied by publisher] (Source: Clinical Breast Cancer)

HER3 Comes of Age: New Insights into Its Functions and Role in Signaling, Tumor Biology, and Cancer Therapy.

Clinical Cancer Research — Tue, 23 Feb 2010 00:00:00 +0100

Authors: Campbell MR, Amin D, Moasser MM The human epidermal growth family (HER) of tyrosine kinase receptors underlies the pathogenesis of many types of human cancer. The oncogenic functions of three of the HER proteins can be unleashed through amplification, overexpression, or mutational activation. This has formed the basis for the development of clinically active targeted therapies. However, the third member HER3 is catalytically inactive, not found to be mutated or amplified in cancers, and its role and functions have remained shrouded in mystery. Recent evidence derived primarily from experimental models now seems to implicate HER3 in the pathogenesis of several types of cancer. Furthermore, the failure to recognize the central role of HER3 seems to underlie resistance to epiderm...

Lapatinib, a Dual EGFR and HER2 Kinase Inhibitor, Selectively Inhibits HER2-Amplified Human Gastric Cancer Cells and is Synergistic with Trastuzumab In vitro and In vivo.

Clinical Cancer Research — Tue, 23 Feb 2010 00:00:00 +0100

CONCLUSION: Together, these data suggest that lapatinib has activity in HER2-amplified upper gastrointestinal cancer and supports the ongoing clinical investigation of lapatinib in patients with HER2-amplified disease. Clin Cancer Res; 16(5); 1509-19. PMID: 20179222 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

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Lapatinib and metronomic capecitabine combination in an HER2-positive inflammatory breast cancer patient: a case report

Annals of Oncology — Mon, 22 Feb 2010 13:25:37 +0100

(Source: Annals of Oncology)

Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer

Annals of Oncology — Mon, 22 Feb 2010 13:25:35 +0100

Conclusions: High Grb7 defines a subset of breast cancer patients with decreased survival, indicating that Grb7 might be a valuable prognostic marker and drug target. Coexpression with HER2/neu indicates that cotargeting these molecules might be an effective approach for treating HER2/neu-positive breast cancers. Future studies using Grb7-targeting agents should include assessment of Grb7 levels. (Source: Annals of Oncology)

An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer

Annals of Oncology — Mon, 22 Feb 2010 13:25:35 +0100

Conclusions: These results demonstrate the safety and efficacy of lapatinib in a broader patient population compared with a clinical trial. (Source: Annals of Oncology)

Antineoplastic effects of an Aurora B kinase inhibitor in breast cancer

Molecular Cancer — Mon, 22 Feb 2010 00:00:00 +0100

Conclusions: We showed that AZD1152 is an effective antineoplastic agent for breast cancer, and our results define a novel mechanism for posttranscriptional regulation of Aurora B after AZD1152 treatment and provide insight into dosing regimen design for this kinase inhibitor in metastatic breast cancer treatment. (Source: Molecular Cancer)

[Adjuvant systemic therapy of early stage breast cancer.]

Orvosi Hetilap — Sat, 20 Feb 2010 06:28:13 +0100

Conclusions: Adjuvant systemic treatment in breast cancer is a rapidly advancing field of clinical oncology. Taxane-based chemotherapy, aromatase inhibitors in the adjuvant endocrine therapy of postmenopausal women, and the availability of trastuzumab as adjuvant treatment have all led to substantial improvement in the outcome of early breast cancer. PMID: 20159750 [PubMed - in process] (Source: Orvosi Hetilap)

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Differences underlying EGFR and HER2 oncogene addiction.

Cell Cycle — Fri, 19 Feb 2010 15:31:02 +0100

Authors: Faber AC, Wong KK, Engelman JA PMID: 20160489 [PubMed - as supplied by publisher] (Source: Cell Cycle)

European CHMP issues positive opinion on extending licence of Tyverb® (lapatinib)

NeLM - News — Fri, 19 Feb 2010 00:00:00 +0100

Source: EMEA Area: News The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has adopted a positive opinion on extending the licence of Tyverb® (lapatinib) to include treatment of patients with breast cancer whose tumours overexpress HER2 (ErbB2), in combination with an aromatase inhibitor in postmenopausal women with hormone receptor-positive metastatic disease, not currently intended for chemotherapy. The patients in the registration study were not previously treated with trastuzumab or an aromatase inhibitor. (Source: NeLM - News)

[Mechanisms of resistance to molecular targeted therapies in breast cancer: update and future.]

Bulletin du Cancer — Fri, 19 Feb 2010 00:00:00 +0100

Authors: Magné N, Chargari C, Conforti R, Toillon RA, Bauduceau O, Védrine L, Khayat D, Spano JP The importance of targeted therapies has been emphasized by clinical trials using antiangiogenic or HER2 inhibitors in breast cancer. First with trastuzumab, it was demonstrated that targeted therapies may improve outcome in patients with HER overexpressing breast cancer in metastatic or adjuvant settings. The emerging role for angiogenesis inhibitors has also been demonstrated with bevacizumab. Unfortunately, there is growing clinical and biological evidence that tumour cells may develop unexpected and complex mechanisms of resistance to those targeted therapies. This review outlines the mechanisms by which tumour cells may resist to new targeted agents. Most recent developments ...

HER2, TOP2A, and TIMP-1 and Responsiveness to Adjuvant Anthracycline-Containing Chemotherapy in High-Risk Breast Cancer Patients [Breast Cancer]

Journal of Clinical Oncology — Thu, 18 Feb 2010 23:00:38 +0100

Conclusion The 2T profile is a more accurate predictor of incremental benefit from anthracycline-containing chemotherapy than HER2, TIMP-1, or TOP2A individually, and compared with these, 2T classifies a larger proportion of patients as sensitive to anthracyclines. (Source: Journal of Clinical Oncology)

Intensive Loading Dose of Trastuzumab Achieves Higher-Than-Steady-State Serum Concentrations and Is Well Tolerated [Breast Cancer]

Journal of Clinical Oncology — Thu, 18 Feb 2010 23:00:37 +0100

Conclusion An intensive loading regimen of trastuzumab achieved higher-than-steady–state serum concentrations during cycle 1, was well tolerated, and had a good efficacy profile. (Source: Journal of Clinical Oncology)

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Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel in HER2-Positive Metastatic Breast Cancer [Breast Cancer]

Journal of Clinical Oncology — Thu, 18 Feb 2010 23:00:37 +0100

Conclusion HTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids. (Source: Journal of Clinical Oncology)

Enzyme presents therapeutic target in breast cancer brain metastasis

Baylor College of Medicine News — Wed, 17 Feb 2010 05:00:00 +0100

The enzyme heparanase plays a critical role in the spread of breast cancer cells to the brain, and, as such, is a promising target for future treatment, said researchers from Baylor College of Medicine and the University of California – Los Angeles, in a report in the current issue of the American Association of Cancer Research journal Molecular Cancer Research . Allows cells to enter circulation, increases proliferation The activity of this enzyme, which degrades the extracellular matrix to allow cells to escape into the surrounding tissue and circulation, is associated with the activation of HER2/epidermal growth factor receptor, said Dr. Dario Marchetti , the senior author of the report that elucidates the enzyme's role in spreading cancer cells to the … (Source: Baylor Coll...

Hormone Receptor and c-ERBB2 Status in Distant Metastatic and Locally Recurrent Breast Cancer: Pathologic Correlations and Clinical Significance.

American Journal of Clinical Pathology — Tue, 16 Feb 2010 16:42:49 +0100

Authors: Idirisinghe PK, Thike AA, Cheok PY, Tse GM, Lui PC, Fook-Chong S, Wong NS, Tan PH Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers in the management of breast carcinoma. They are not always analyzed in distant metastatic and locally recurrent breast cancers. We compared immunohistochemical expression in a series of primary breast carcinomas with their distant metastases (n = 72) and local recurrences (n = 45) and analyzed the impact of any changes on survival. Discordance rates between primary and metastatic and between primary and locally recurrent lesions, respectively, were 18% (13/72) and 13% (6/45) for ER, 42% (30/72) and 33% (15/45) for PR, and 7% (5/72) and 2% (1/45) for c-ERBB2. There wa...

Poverty link to cancer survival

NHS News Feed — Tue, 16 Feb 2010 10:20:00 +0100

Conclusion These findings appear to suggest that part of the reason why women with breast cancer from deprived areas have worse overall survival and disease-free survival, may be related to mutations in the p53 gene. Exactly how socio-economic status interacts with the p53 gene to have this effect is not clear and will require further investigation. Other points to note about the current study are that: The measure of the women’s level of deprivation was based on the women’s postcode. Though this is an accepted method for measuring deprivation, it may not give as exact a measure as a more thorough assessment of individual women’s socio-economic characteristics (e.g. household income, education and so on). The study was relatively small, with few women in the most deprived categ...

A fuzzy gene expression-based computational approach improves breast cancer prognostication

BioMed Central — Mon, 15 Feb 2010 00:00:00 +0100

Early gene expression studies classified breast tumors into at least three clinically relevant subtypes. Although most current gene signatures are prognostic for estrogen receptor (ER) positive/ human epidermal growth factor receptor 2 (HER2) negative breast cancers, few are informative for ER negative/HER2 negative and HER2 positive subtypes. Here we present Gene Expression Prognostic Index Using Subtypes (GENIUS), a fuzzy approach for prognostication that takes into account the molecular heterogeneity of breast cancer. In systematic evaluations, GENIUS significantly outperformed current gene signatures and clinical indices in the global population of patients. (Source: BioMed Central)

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Integration of Biomarkers Including Molecular Targeted Therapies in Head and Neck Cancer

Head and Neck Pathology — Sat, 13 Feb 2010 06:51:53 +0100

Abstract Head and neck tumors comprise a wide spectrum of heterogeneous neoplasms for which biomarkers are needed to aid in earlier diagnosis, risk assessment and therapy response. The search for biomarkers includes evaluation of tumor tissues and surrogate materials by molecular, genomic and phenotypic means. Ideal biomarkers should be accurate and easy to perform, highly specific, objective, quantitative, and cost effective. Because of the heterogeneity of head and neck tumors, the integration of multiple selected markers in association with the histopathologic features is advocated for risk assessment. For targeted therapy, however, a single key molecule must be identified. Key molecules and pathways for targeted therapy include growth factor receptors, MAPk/ERk pathway...

Increased estrogen sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1(17β-HSD1) following neoadjuvant aromatase inhibitor therapy in breast cancer patients

Breast Cancer Research and Treatment — Fri, 12 Feb 2010 07:12:02 +0100

Abstract Aromatase inhibitors (AIs) are considered the gold standard for endocrine therapy of estrogen receptor (ER) positive postmenopausal breast cancer patients. The therapy may enhance therapeutic response and stabilize disease but resistance and disease progression inevitably occur in the patients. These are considered at least partly due to an emergence of alternative intratumoral estrogen production pathways. Therefore, in this study we evaluated effects of exemestane (EXE) upon the enzymes involved in intratumoral estrogen production including estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), and estrogen sulfotransferase (EST) and correlated the findings with therapeutic responses including Ki67 labeling index (Ki67). 116 postmenopausa...

Association between vitamin D and calcium intake and breast cancer risk according to menopausal status and receptor status in Japan

Cancer Science — Fri, 12 Feb 2010 00:00:00 +0100

We examined 1803 breast cancer patients and 3606 age- and menopausal status-matched noncancer controls. Among cases, 713 were assessed for ER, PR, and HER2 status. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional or unconditional logistic models adjusted for potential confounders. A significant inverse association was observed between vitamin D and calcium intake and breast cancer risk among all subjects, with top quartile ORs of 0.76 (95% CI, 0.63[ndash]0.90; trend P = 0.001) and 0.83 (95% CI, 0.69[ndash]0.99; trend P = 0.038), respectively. In analyses stratified by menopausal status, a significant association between risk and vitamin D was observed only among premenopausal women (trend P < 0.001), whereas that between risk and calcium intake was see...

Estrogen receptor positive breast cancers in BRCA1 mutation carriers: clinical risk factors and pathologic features

Breast Cancer Research — Thu, 11 Feb 2010 00:00:00 +0100

IntroductionMost breast cancers that occur in women with germline BRCA1 mutations are estrogen receptor-negative (ER-) and also typically lack expression of progesterone receptor (PR) and HER2 overexpression. We undertook a study to assess the clinical factors that predict for an estrogen receptor positive (ER+) breast cancer in BRCA1 mutation carriers and to characterize the pathologic features of these tumors. Methods: Clinical characteristics of BRCA1 carriers with 58 ER+ and 114 ER- first invasive breast cancers were compared. Pathologic features of BRCA1 ER+ cancers were compared to those of BRCA1 ER- cancers and to age-matched ER+ sporadic cancers. Results: BRCA1 carriers age [greater than or equal to] 50 at diagnosis of first invasive breast cancer were more likely to have an ER+ ca...

Trastumab (Herceptin®) approved in UK for treatment of gastric cancer

NeLM - News — Thu, 11 Feb 2010 00:00:00 +0100

Source: PharmaTimes, eMC (electronic Medicines Compendium) Area: News Trastumab (Herceptin®) has been approved in the UK for the treatment of gastric cancer. It is licensed for use in combination with capecitabine or 5-fluorouracil and cisplatin for the treatment of patients with HER2 positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction who have not received prior anti-cancer treatment for their metastatic disease. It should only be used in patients with metastatic gastric cancer whose tumours have HER2 overexpression as defined by IHC2+ and a confirmatory FISH+ result, or IHC 3+, as determined by an accurate and validated assay. NICE is due to assess use of trastuzumab in this setting in 2010, with guidance anticipated by the end of the year. (Source: NeLM - N...

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Multichromatic phenotyping of HER receptor coexpression in breast tumor tissue samples using flow cytometry - Possibilities and limitations

Cytometry Part A — Thu, 11 Feb 2010 00:00:00 +0100

The prognostic significance of HER2 expression in human breast carcinomas is beyond dispute nowadays. The HER family of receptor tyrosine kinases comprises four members (HER1/ErbB1/EGFR, HER2/ErbB2, HER3/ErbB3, and HER4/ErbB4) that act in concert via transactivation and consequently compose a functional signaling unit. Besides HER2 overexpression, coexpression of other HER receptors has substantial impact on course of disease and potential therapeutic benefit. This observation is substantiated by numerous preclinical studies and retrospective studies done on patients with breast cancer. Against this background, the quantification of all HER receptor expressions at the same time would significantly extend the information content revealed by routine diagnosis of breast cancer tissues. Moreov...

Multiplexed Assessment of the Southwest Oncology Group-Directed Intergroup Breast Cancer Trial S9313 by AQUA Shows That Both High and Low Levels of HER2 Are Associated with Poor Outcome.

The American Journal of Pathology — Thu, 11 Feb 2010 00:00:00 +0100

Authors: Harigopal M, Barlow WE, Tedeschi G, Porter PL, Yeh IT, Haskell C, Livingston R, Hortobagyi GN, Sledge G, Shapiro C, Ingle JN, Rimm DL, Hayes DF Assessment of key breast cancer tissue biomarkers is often done using nonquantitative methods. We hypothesized that use of continuous analysis of expression with the AQUA method of automated quantitative analysis will provide prognostic information beyond that attainable with conventional methods. A tissue microarray was made from 2123 of 3122 patients accrued to SWOG 9313, in which sequential doxorubicin (A) and cyclophosphamide (C) was compared with combination AC and in which all patients except premenopausal estrogen receptor (ER)-negative patients received tamoxifen. Multiplexed assays of 1) HER2 and estrogen receptor and 2) proge...

Curis Publishes CUDC-101 Medicinal Chemistry Data

Drugs.com - Clinical Trials — Wed, 10 Feb 2010 13:35:05 +0100

Publication in Journal of Medicinal Chemistry Highlights Curis' Novel, First-in-Class Cancer Drug that Selectively Targets HDAC, EGFR and Her2 Simultaneously CAMBRIDGE, Mass.--(BUSINESS WIRE)--Feb 10, 2010 - Curis, Inc. (NASDAQ: CRIS), a drug... (Source: Drugs.com - Clinical Trials)

Familial relative risks for breast cancer by pathological subtype: a population-based cohort study

Breast Cancer Research — Wed, 10 Feb 2010 00:00:00 +0100

Conclusions: FRR for breast cancer was significantly increased for both ER-negative and ER-positive disease. Including receptor status in conjunction with genetic status may aid risk prediction in women with a family history. (Source: Breast Cancer Research)

Aggressive progression of breast cancer with microscopic pulmonary emboli possessing a stem cell-like phenotype independent of its origin

Pathology International — Wed, 10 Feb 2010 00:00:00 +0100

Microscopic pulmonary tumor embolism is difficult to diagnose. Herein is presented the case of a patient who suffered from acute dyspnea and breast cancer on the right side. Two weeks after the breast cancer diagnosis the patient began to experience dyspnea. After 2 weeks of dyspnea, the patient died without an accurate diagnosis of dyspnea. Autopsy indicated massive microscopic pulmonary emboli of the breast cancer. Immunohistochemistry showed that most of the cancer cells in the primary site were negative for estrogen receptors, progesterone receptors Her2/neu oncogene (triple negative), and stem cell-like markers (OCT3/4, NANOG2, CD44, CD24, aldehyde dehydrogenase 1 (ALDH1)). The breast cancer cells in the lung (the metastasized site), however, were triple negative, but were enriched in...

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Discovery of 7-(4-(3-Ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a Potent Multi-Acting HDAC, EGFR, and HER2 Inhibitor for the Treatment of Cancer

Journal of Medicinal Chemistry — Tue, 09 Feb 2010 13:23:16 +0100

Journal of Medicinal Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Medicinal Chemistry)

Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue

BMC Cancer — Tue, 09 Feb 2010 00:00:00 +0100

Conclusions: Scores representing the endocrine responsiveness and proliferation status of breast cancers were developed from gene expression analyses based on RNA derived from FFPE tissues. The validation of the molecular scores with tumor samples of participants of the BIG 1-98 trial demonstrates that such scores can serve as independent prognostic factors to estimate disease free survival (DFS) in postmenopausal patients with estrogen receptor positive breast cancer.Current Controlled Trials: NCT00004205 (Source: BMC Cancer)

AZD8931, an Equipotent, Reversible Inhibitor of Signaling by Epidermal Growth Factor Receptor, ERBB2 (HER2), and ERBB3: A Unique Agent for Simultaneous ERBB Receptor Blockade in Cancer.

Clinical Cancer Research — Tue, 09 Feb 2010 00:00:00 +0100

CONCLUSIONS: AZD8931 has a unique pharmacologic profile providing equipotent inhibition of EGFR, erbB2, and erbB3 signaling and showing greater antitumor activity than agents with a narrower spectrum of erbB receptor inhibition in specific preclinical models. AZD8931 provides the opportunity to investigate whether simultaneous inhibition of erbB receptor signaling could be of utility in the clinic, particularly in the majority of solid tumors that do not overexpress erbB2. Clin Cancer Res; 16(4); 1159-69. PMID: 20145185 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Chromosome 17 Polysomy without Human Epidermal Growth Factor Receptor 2 Amplification Does Not Predict Response to Lapatinib Plus Paclitaxel Compared with Paclitaxel in Metastatic Breast Cancer.

Clinical Cancer Research — Tue, 09 Feb 2010 00:00:00 +0100

CONCLUSION: This analysis could not confirm the hypothesis that Chr-17 polysomy in HER2-nonamplified patients improved chemotherapy outcome when lapatinib is added as a HER2-targeted treatment. Clin Cancer Res; 16(4); 1281-8. PMID: 20145176 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Fluorescent In Situ Hybridization As a Primary Test for HER2 Status in Breast Cancer: Controversies [CORRESPONDENCE]

Journal of Clinical Oncology — Mon, 08 Feb 2010 23:01:41 +0100

(Source: Journal of Clinical Oncology)

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High-grade breast cancers include both highly sensitive and highly resistant subsets to cytotoxic chemotherapy

Journal of Cancer Research and Clinical Oncology — Mon, 08 Feb 2010 17:29:10 +0100

Conclusions High-grade breast cancers include both highly sensitive and highly resistant subsets to cytotoxic chemotherapy. Three factors can help discriminate between these subsets. HR-negative and HER2-positive can be predictive of high chemosensitivity. Advanced primary tumor stage can be predictive of high chemoresistance. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00432-010-0798-7Authors Tomo Osako, Japanese Foundation for Cancer Research Divisions of Pathology, Cancer Institute Hospital 3-8-31, Ariake, Koto-ku Tokyo 135-8550 JapanRie Horii, Japanese Foundation for Cancer Research Divisions of Pathology, Cancer Institute Hospital 3-8-31, Ariake, Koto-ku Tokyo 135-8550 JapanMasaaki Matsuura, Japanese Foundation for Cancer Research Divisions of...

Epidermal growth factor-dependent enhancement of invasiveness of squamous cell carcinoma of the breast

Cancer Science — Mon, 08 Feb 2010 00:00:00 +0100

Factors that promote the aggressiveness of squamous cell carcinoma of the breast are not well understood. To examine the involvement of cell motility and the mechanism of this behavior, a squamous cell carcinoma cell line of the breast (HBC9) was established from a metastatic lymph node of a Japanese woman. HBC9 expressed epidermal growth factor receptor (EGFR), but was negative for Her2 or Her3.The invasive ability of HBC9 was compared with that of four breast ductal carcinoma cell lines by Matrigel invasion assay. EGF stimulation induced the formation of surface protrusions and cell migration in HBC9 cells, and significantly increased the number of cells migrating through the Matrigel. The invasive ability of HBC9 was compared with other cell lines of breast carcinoma; it was much greate...

The HER2 testing conundrum

Nature Biotechnology — Sat, 06 Feb 2010 17:26:06 +0100

Nature Biotechnology 28, 117 (2010). doi:10.1038/nbt0210-117 Author: Malorye Allison Problems in interpreting diagnostic tests for HER2 may be compromising patient access to effective treatments. As new versions of therapies targeting HER2 work their way through clinical trials, will the situation get even murkier? Malorye Allison investigates. (Source: Nature Biotechnology)

Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy.

Biomaterials — Sat, 06 Feb 2010 00:00:00 +0100

We report here an aqueous based formulation of glycerol monooleate coated magnetic nanoparticles (GMO-MNPs) devoid of any surfactant capable of carrying high payload hydrophobic anticancer drugs. The biocompatibility was confirmed by tumor necrosis factor alpha assay, confocal microscopy. High entrapment efficiency approximately 95% and sustained release of encapsulated drugs for more than two weeks under in vitro conditions was achieved for different anticancer drugs (paclitaxel, rapamycin, alone or combination). Drug loaded GMO-MNPs did not affect the magnetization properties of the iron oxide core as confirmed by magnetization study. Additionally the MNPs were functionalized with carboxylic groups by coating with DMSA (Dimercaptosuccinic acid) for the supplementary conjugation of amines...

The molecular mechanism of Vav3 oncogene on upregulation of androgen receptor activity in prostate cancer cells.

International Journal of Oncology — Thu, 04 Feb 2010 21:22:39 +0100

Authors: Liu Y, Wu X, Dong Z, Lu S Our previous studies revealed that Vav3 oncogene is overexpressed in human prostate cancer, enhances androgen receptor (AR)-mediated signaling, and may play a role in prostate cancer development and progression. The purpose of this study was to determine the molecular mechanisms responsible for AR activation by Vav3. We found that interaction between N-terminus and C-terminus of AR is essential for its elevated activity stimulated by Vav3. The DH and PH domains of Vav3 are involved in direct interaction with AR. Both cytoplasmic and nuclear levels of AR and Vav3 are elevated and their nuclear localization is further stimulated by DHT in androgen-independent LNCaP-AI cells relative to their parental androgen-dependent LNCaP cells. Vav3 is colocalized w...

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Bioactivity and molecular targets of novel substituted quinolines in murine and human tumor cell lines in vitro.

International Journal of Oncology — Thu, 04 Feb 2010 21:22:24 +0100

In conclusion, antiproliferative PQ1 is effective against a spectrum of tumor cells and might interact with various membrane and nuclear targets to enhance gap junctions, inhibit nucleoside transport and block cytokinesis but does not appear to disrupt the EGF receptor-mediated signaling pathways to induce growth arrest and apoptosis. PMID: 20126988 [PubMed - in process] (Source: International Journal of Oncology)

Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up

Breast Cancer Research and Treatment — Thu, 04 Feb 2010 18:13:39 +0100

Abstract Triple-negative breast cancer (TNB) has poor prognosis and moreover patients with TNB do not benefit from established targeted drugs with endocrine therapy or trastuzumab. The aim of the study was to analyze the prevalence of candidate biomarkers in tumors from patients with TNB. Tissue microarrays were prepared from primary tumors from premenopausal breast cancer patients (500/564) randomized to adjuvant tamoxifen or no adjuvant treatment. Immunohistochemical (IHC) staining included ER, PR, HER2, epidermal receptor growth factor (EGFR), vascular endothelial growth factor A (VEGF-A), and vascular endothelial growth factor receptor 2 (VEGFR2). EGFR and HER2 gene copy number was defined by fluorescence in situ hybridization (FISH). All patients were included in the ...

Multiplex ligation-dependent probe amplification to detect HER2 amplification in breast cancer: New insights in optimal cut-off value.

Cellular Oncology — Thu, 04 Feb 2010 00:00:00 +0100

Authors: Moelans CB, de Weger RA, van Diest PJ PMID: 20208145 [PubMed - as supplied by publisher] (Source: Cellular Oncology)

Association between HER2, TOP2A, and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer

Breast Cancer Research and Treatment — Wed, 03 Feb 2010 17:57:58 +0100

Abstract In breast cancer, recent studies suggest that the value of HER2 for predicting response to anthracycline-based chemotherapy may be more likely related to the concomitant amplification of the TOP2A gene. Here, we study the association between HER2 or TOP2A status and response to anthracycline-based preoperative chemotherapy and explore the interaction between HER2 or TOP2A status and intense dose-dense (IDD) chemotherapy. HER2 and TOP2A gene alterations were quantified by fluorescence in situ hybridization in primary tumor core biopsies from 373 high-risk primary breast cancer patients (tumors ≥3 cm or inflammatory) that received an IDD or conventionally scheduled anthracycline-based preoperative chemotherapy. HER2 was amplified in 94/350 tumors (27%) of whi...

PIKing the right isoform: the emergent role of the p110β subunit in breast cancer

Virchows Archiv — Wed, 03 Feb 2010 17:55:55 +0100

Abstract Class IA phosphoinositide-3’-kinases (PI3Ks) regulate many cellular processes. Despite a clear implication of PI3K in cancer, the involvement of each of its isoforms namely p110α and p110β in the development of breast cancer remains elusive. Until recently, the spotlight was given to the α subunit; however, the p110β isoform has now emerged as an interesting target as well. In order to determine the importance of both these subunits in breast cancer, we aimed to study the expression of p110α and p110β in a series of invasive breast carcinomas. We constructed tissue microarrays from 315 invasive breast carcinomas and performed immunohistochemistry for p110α and β, correlating the expression patterns with clinicopathological parameters. Furthermore, overal...

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A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer

Cancer Chemotherapy and Pharmacology — Wed, 03 Feb 2010 17:55:10 +0100

Abstract The optimal adjuvant treatment for gastric cancer remains controversial. We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen, in patients with high-risk gastric cancer, with that of the same chemotherapy plus radiation therapy (RT). In addition, we evaluated the prognostic and/or predictive value of a panel of molecular markers. Patients with histologically proven, radically resected gastric cancer, stage ≥T3 and/or N+ were randomized to 6 cycles of docetaxel with cisplatin, both at 75 mg/m2 every 3 weeks (arm A) or the same treatment with RT (arm B; 45 Gy). Due to excessive nausea and vomiting, cisplatin was substituted by carboplatin at AUC (area under the curve) of 5 after the first 45 patients (22 group ...

A HER2-binding Affibody molecule labelled with 68Ga for PET imaging: direct in vivo comparison with the 111In-labelled analogue

European Journal of Nuclear Medicine and Molecular Imaging — Wed, 03 Feb 2010 17:54:56 +0100

Conclusion 68Ga-ABY-002 is easy to label and provides high-contrast imaging within 2 h after injection. This makes it a promising candidate for clinical molecular imaging of HER2 expression in malignant tumours. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00259-009-1367-7Authors Vladimir Tolmachev, Uppsala University Division of Biomedical Radiation Sciences, Rudbeck Laboratory 751 81 Uppsala SwedenIrina Velikyan, Uppsala University Department of Biochemistry and Organic Chemistry Uppsala SwedenMattias Sandström, Uppsala University Hospital Hospital Physics, Department of Oncology Uppsala SwedenAnna Orlova, Uppsala University Division of Biomedical Radiation Sciences, Rudbeck Laboratory 751 81 Uppsala Sweden Journal European Journal...

Feasibility of FDG PET/CT to monitor the response of axillary lymph node metastases to neoadjuvant chemotherapy in breast cancer patients

European Journal of Nuclear Medicine and Molecular Imaging — Wed, 03 Feb 2010 17:54:56 +0100

Conclusion The high accuracy in visualizing lymph node metastases and the sufficiently high SUVmax and tumour to background ratio at baseline suggest that it is feasible to monitor the axillary response with FDG PET/CT, especially in triple-negative tumours. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00259-009-1343-2Authors Marieke E. Straver, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital Department of Surgical Oncology Plesmanlaan 121 1066 CX Amsterdam The NetherlandsTjeerd S. Aukema, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital Department of Nuclear Medicine Plesmanlaan 121 1066 CX Amsterdam The NetherlandsRenato A. Valdes Olmos, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital Depart...

Neoadjuvant Trastuzumab for Locally Advanced Breast Cancer: NOAH Results

Medscape Internal Medicine Headlines — Wed, 03 Feb 2010 15:40:52 +0100

When should trastuzumab be started in women with either HER2-positive locally advanced breast cancer or inflammatory breast cancer? Medscape Medical News (Source: Medscape Internal Medicine Headlines)

Synchronous Ovarian Cancer in a Patient with Pleomorphic Lobular Breast Cancer: A Therapeutic Dilemma

Clinical Oncology — Wed, 03 Feb 2010 15:36:35 +0100

Sir — A 49-year-old premenopausal female patient presented with a breast lump and abdominal distention. Her personal history was unremarkable and a family history revealed ovarian cancer in her aunt and thyroid cancer in her brother. On physical examination, a 4cm mass in her right breast and an axillary fixed lymphadenopathy of 2cm were palpated and ascites was detected. Biopsy from the breast lump showed pleomorphic lobular carcinoma, grade 3, oestrogen receptor and progesterone receptor were both positive with HER2 overexpression immunohistochemically. Abdominal computed tomography revealed peritoneal carcinomatosis, ascites and a 15mm left ovarian cyst. A chest X-ray and a bone scan were normal. Diagnostic paracentesis was carried out to rule out a second intra-abdominal malignancy a...

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Immunohistochemical surrogate markers of breast cancer molecular classes predicts response to neoadjuvant chemotherapy

Cancer — Wed, 03 Feb 2010 00:00:00 +0100

Complete pathologic response to neoadjuvant chemotherapy (NACT) is predominantly seen in "ERBB2" and "basal-like" tumors using expression profiling. We hypothesize that a similar response could be predicted using semiquantitative immunohistochemistry for estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2).ER, PR, and HER2 were used to classify 359 tumors treated with NACT into 6 groups: luminal A (strong ER+, HER2 negative), luminal B (weak to moderate ER+, HER2 negative), triple negative (negative for ER, PR, and HER2), ERBB2 (negative for ER and PR, but HER2+), luminal A-HER2 hybrid (strong ER+ and HER2+), and luminal B-HER2 hybrid (weak to moderate ER+ and HER2+). Complete pathologic response was defined as absence of invasive carcin...

Male breast cancer: An update in diagnosis, treatment and molecular profiling

Maturitas — Wed, 03 Feb 2010 00:00:00 +0100

Abstract: Significant advances have been made in the diagnosis and treatment of female breast cancer, resulting in a decline in incidence and a global improvement in clinical outcome. The statistics for male breast cancer (MBC) stand in sharp contrast—over the past several decades, there has been a steady rise in the incidence of this disease, and clinical outcome has improved at a much slower pace. In the current review, the clinicopathologic features of MBC are described in detail. An emphasis is placed on molecular profiling of MBC, which may identify candidate biomarkers and putative targets for pharmacologic intervention. The current role of cytotoxic chemotherapy and endocrine therapy (including tamoxifen, aromatase inhibitors and GnRH analogues) is defined in the context of curren...

Trastuzumab Approved for HER-2 Gastric Cancer in Europe

Medscape Today Headlines — Tue, 02 Feb 2010 20:49:09 +0100

This is the first approval for a label extension for trastuzumab, which is already marketed for the treatment of HER2-positive breast cancer. Medscape Medical News (Source: Medscape Today Headlines)

Trastuzumab Approved for HER2 Gastric Cancer in Europe

Medscape Hematology-Oncology Headlines — Tue, 02 Feb 2010 20:49:09 +0100

This is the first approval for a label extension for trastuzumab, which is already marketed for the treatment of HER2-positive breast cancer. Medscape Medical News (Source: Medscape Hematology-Oncology Headlines)

GSK's TYKERB(R) Receives Accelerated Approval For First-Line Combination Treatment Of Metastatic Breast Cancer

Health News from Medical News Today — Tue, 02 Feb 2010 09:00:00 +0100

GlaxoSmithKline (NYSE: GSK) announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for a new combination regimen using TYKERB® (lapatinib) as a first-line, all-oral treatment for women with metastatic breast cancer. TYKERB is now indicated in combination with letrozole for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated... (Source: Health News from Medical News Today)

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Phase II trial of pertuzumab and trastuzumab in patients with metastatic breast cancer that progressed during prior trastuzumab therapy

NeLM - News — Tue, 02 Feb 2010 00:00:00 +0100

Source: JCO Area: News Pertuzumab, an investigational human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibody, and the approved HER2-targeted monoclonal antibody trastuzumab have complementary mechanisms of action and have the potential to enhance antitumor activity when combined. This phase II trial assessed the efficacy and safety profile of the combination in patients with HER2-positive breast cancer whose disease had progressed during prior trastuzumab-based therapy. In this multicentre, open-label, single-arm, two-stage study, 66 patients with advanced HER2-positive breast cancer in whom disease progression had occurred during prior trastuzumab-based therapy received trastuzumab weekly (4 mg/kg loading dose, then 2 mg/kg every week) or every 3 weeks (...

Management of breast cancer with targeted agents: importance of heterogenicity

Nature Clinical Practice Oncology — Tue, 02 Feb 2010 00:00:00 +0100

Authors: Serena Di Cosimo & José Baselga Breast cancer is a heterogeneous disease with different molecular drivers regulating its growth, survival and response to therapy. Breast cancer is divided in three major subtypes based on the pattern of expression of hormone receptors and HER2: luminal tumors (or HR positive), HER2 amplified (Source: Nature Clinical Practice Oncology)

FDA Approves Lapatinib/Letrozole Combination for Advanced Breast Cancer

Medscape Today Headlines — Mon, 01 Feb 2010 21:46:00 +0100

The FDA has approved an expanded indication for lapatinib in combination with letrozole for the treatment of hormone-positive and HER2-positive advanced breast cancer in certain postmenopausal women. Medscape Medical News (Source: Medscape Today Headlines)

Trastuzumab: A Review of its Use as Adjuvant Treatment in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer

Drugs — Mon, 01 Feb 2010 14:23:30 +0100

(Source: Drugs)

FDA Okays Drug Combo for Advanced Breast Cancer

MedPage Today Product Alert — Mon, 01 Feb 2010 13:13:14 +0100

The FDA has approved a combination of lapatinib (Tykerb) and letrozole (Femara) to treat hormone-positive and HER2-positive advanced breast cancer in postmenopausal women. (Source: MedPage Today Product Alert)

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FDA Expands Use Of Approved Breast Cancer Drug

Health News from Medical News Today — Mon, 01 Feb 2010 11:00:00 +0100

The U.S. Food and Drug Administration approved Tykerb (lapatinib) in combination with Femara (letrozole) to treat hormone positive and HER2-positive advanced breast cancer in postmenopausal women for whom hormonal therapy is indicated. HER2 is a protein involved in normal cell growth. It is found on some types of cancer cells, including breast cancer cells. In hormone positive breast cancer, the presence of certain hormones contributes to breast cancer growth. In HER2-positive breast cancer, stimulation of the HER2 receptor contributes to cancer cell growth... (Source: Health News from Medical News Today)

FDA Expands Use Of Approved Breast Cancer Drug

Breast Cancer News From Medical News Today — Mon, 01 Feb 2010 11:00:00 +0100

AC480, formerly BMS-599626, a pan Her inhibitor, enhances radiosensitivity and radioresponse of head and neck squamous cell carcinoma cells in vitro and in vivo

Investigational New Drugs — Mon, 01 Feb 2010 06:46:32 +0100

Conclusion: AC480 significantly enhanced the radiosensitivity of HN-5 cells, expressing both EGFR and Her2. The mechanisms involved in the enhancement included cell cycle redistribution and inhibition of DNA repair. Both in vitro and in vivo data from our study suggest that AC480 has potential to increase tumor response to radiotherapy. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-010-9389-3Authors Mylin A. Torres, Winship Cancer Institute of Emory University Department of Radiation Oncology Atlanta GA USAUma Raju, The University of Texas MD Anderson Cancer Center Department of Experimental Radiation Oncology Houston TX USADavid Molkentine, The University of Texas MD Anderson Cancer Center Department of Experimental Radiation Oncology Houston TX USAOliv...

Herceptin 150mg vial (trastuzumab) - Licence extension

NeLM - SPC Changes — Mon, 01 Feb 2010 00:00:00 +0100

Source: Manufacturer notification Area: Other Library Updates > SPC Changes The revised SmPC contains the following new indication for Herceptin (trastuzumab): . Herceptin in combination with capecitabine or 5-fluorouracil and cisplatin is indicated for the treatment of patients with HER2 positive metastatic adenocarcinoma of the stomach or gastrooesophageal junction who have not received prior anti cancer treatment for their metastatic disease. . Herceptin should only be used in patients with metastatic gastric cancer whose tumours have HER2 overexpression as defined by IHC2+ and a confirmatory FISH+ result, or IHC 3+, as determined by an accurate and validated assay. Revision of section 4.2 Posology and method of administration for early breast cancer 3 weekly schedule: The informat...

Trastuzumab with either docetaxel or vinorelbine as first-line treatment for patients with HER2-positive advanced breast cancer: a retrospective comparison

BMC Cancer — Mon, 01 Feb 2010 00:00:00 +0100

Background: Combinations of trastuzumab with either docetaxel or vinorelbine are considered valuable treatment options for HER2-positive metastatic breast cancer patients. We performed a retrospective comparison of the clinical outcomes associated with either one of these combinations. Methods: From a multi-institutional database we retrieved 179 patients treated with either docetaxel or vinorelbine plus trastuzumab as first-line therapy for HER2-positive advanced breast cancer. Results: Docetaxel-trastuzumab was superior to vinorelbine-trastuzumab in terms of response rate (RR: 77 vs 57%, p=0.01) and median overall survival (OS: 35 vs 23 months, p=0.04), but not in median time to progression (TTP: 12 vs 10 months, p=0.53). At multivariate analysis, type of treatment was not associated wit...

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FDA approves expanded use of lapatinib in breast cancer

NeLM - News — Mon, 01 Feb 2010 00:00:00 +0100

Source: FDA Area: News The US FDA has approved lapatinib (Tykerb®) for use in combination with letrozole (Femara®) in the treatment of hormone-positive and HER2-positive advanced breast cancer in postmenopausal women for whom hormonal therapy is indicated. In a company-sponsored study, women with HER2-positive breast cancer were randomised to receive lapatinib plus letrozole or letrozole alone. Those in the combination treatment arm had a longer progression free survival (35 weeks) than those in the letrozole monotherapy arm (13 weeks). Mature data on overall survival are not yet available. [No further study details are reported in the summary.] Lapatinib was initially approved for use in combination with capecitabine in women wi...

Is It Too Soon To Start Reporting HER2 Genetic Heterogeneity?

Archives of Pathology and Laboratory Medicine — Mon, 01 Feb 2010 00:00:00 +0100

Authors: Albarracin C, Edgerton ME, Gilcrease MZ, Huo L, Krishnamurthy S, Middleton LP, Resetkova E, Sahin AA, Sneige N, Fraser WS, Wu Y PMID: 20121597 [PubMed - in process] (Source: Archives of Pathology and Laboratory Medicine)

Proposal of Modification for the Definition of Genetic Heterogeneity in HER2 Testing in Breast Cancer.

Archives of Pathology and Laboratory Medicine — Mon, 01 Feb 2010 00:00:00 +0100

Authors: Hsu CY, Li AF, Yang CF, Ho DM PMID: 20121596 [PubMed - in process] (Source: Archives of Pathology and Laboratory Medicine)

In Vivo Imaging of Xenograft Tumors Using an Epidermal Growth Factor Receptor-Specific Affibody Molecule Labeled with a Near-infrared Fluorophore.

Neoplasia — Mon, 01 Feb 2010 00:00:00 +0100

In conclusion, Eaff molecule labeled with a NIR fluorophore is a promising molecular imaging agent for EGFR-overexpressing tumors. PMID: 20126472 [PubMed - in process] (Source: Neoplasia)

A Phase II Neoadjuvant Trial of Sequential Nanoparticle Albumin-Bound Paclitaxel Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide in Locally Advanced Breast Cancer.

Clinical Genitourinary Cancer — Mon, 01 Feb 2010 00:00:00 +0100

Conclusion: Albumin-bound paclitaxel given over 12 weeks is well tolerated. Albumin-bound paclitaxel should be further evaluated in a randomized setting in both adjuvant and neoadjuvant trials. PMID: 20133263 [PubMed - in process] (Source: Clinical Genitourinary Cancer)

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Pathologic Complete Response to Preoperative Sequential Doxorubicin/Cyclophosphamide and Single-Agent Taxane With or Without Trastuzumab in Stage II/III HER2-Positive Breast Cancer.

Clinical Genitourinary Cancer — Mon, 01 Feb 2010 00:00:00 +0100

Conclusion: Sequential administration of preoperative doxorubicin and cyclophosphamide followed by a taxane and trastuzumab combination is safe in women with primary operable HER2+ breast cancer and is associated with a high pCR rate. Large randomized phase III clinical trials are evaluating the role of preoperative trastuzumab when added to anthracycline- and/or taxane-based regimens. PMID: 20133257 [PubMed - in process] (Source: Clinical Genitourinary Cancer)

Where to With HER2?

Clinical Genitourinary Cancer — Mon, 01 Feb 2010 00:00:00 +0100

Authors: Sledge GW PMID: 20133253 [PubMed - in process] (Source: Clinical Genitourinary Cancer)

Understanding resistance to endocrine agents: molecular mechanisms and potential for intervention.

Clinical Genitourinary Cancer — Mon, 01 Feb 2010 00:00:00 +0100

Conclusion: Our data suggest that inhibition of both the HER2 and estrogen signaling pathways is required to prolong the responsiveness of the tumors to endocrine therapies. In addition, we have shown that HER2 upregulation is an adaptive process that the tumors undergo during continued letrozole treatment, which is reversed upon removal of the treatment. The tumors regain responsiveness to letrozole after a short period "off" treatment. These studies suggest that by reversing the resistance to hormone therapy, patients could have a second response and could delay the need for chemotherapy. PMID: 20133251 [PubMed - in process] (Source: Clinical Genitourinary Cancer)

Metastatic prostatic adenocarcinoma mimicking inflammatory breast carcinoma: a case report.

Clinical Genitourinary Cancer — Mon, 01 Feb 2010 00:00:00 +0100

We present a case of a man who presented with breast skin changes that mimicked inflammatory breast carcinoma with specialized testing ultimately giving a diagnosis of metastatic prostatic adenocarcinoma. A 78-year-old man presented with left breast redness and swelling. Examination revealed an erythematous rash with subcutaneous edema over the left hemithoracic area. A breast ultrasound showed no focal mass, and a breast core biopsy had no evidence of tumor. A skin biopsy showed metastatic carcinoma in dermal lymphatics, and the tumor was found to have no estrogen or progesterone receptors or HER2 expression. Computed tomography scans, positron emission tomography, and a nuclear bone scan revealed widespread skeletal metastases. The patient received a 3-month course of capecitabine and cy...

Neuroendocrine differentiation in breast cancer: established facts and unresolved problems

Seminars in Diagnostic Pathology — Mon, 01 Feb 2010 00:00:00 +0100

Neuroendocrine breast carcinoma (NEBC) diagnosis relies on (i) presence of morphologic neuroendocrine features, and (ii) neuroendocrine markers expressed in more than 50% of tumor cells. The World Health Organization classification describes 3 main histologic types: the solid, the small/oat cell, and the large cell variant. In addition, we have recently proposed a further categorization into 5 subgroups: the first 3 categories encompass solid lesions and include (i) solid cohesive carcinomas, (ii) alveolar carcinomas, and (iii) small cell carcinoma; the last subgroups include mucin-producing tumors which are (iv) solid papillary carcinomas and (v) cellular mucinous carcinomas. Chromogranin A and synaptophysin have been considered as the most sensitive and specific neuroendocrine markers in...

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Prediction of recurrence risk in early breast cancer using human epidermal growth factor 2 and cyclin A2.

Chinese Medical Journal — Mon, 01 Feb 2010 00:00:00 +0100

CONCLUSIONS: Cyclin A2 and HER2 are associated with proliferation and high recurrence, particularly when combined. Cyclin A2 is easily detected by nuclear staining and might be a useful biomarker for recurrence risk in HER2 negative patients. PMID: 20193482 [PubMed - in process] (Source: Chinese Medical Journal)

Traztuzumab improves outcome of HER2-positive locally advanced or inflammatory breast cancer

MedWire News - Breast Cancer — Sat, 30 Jan 2010 13:47:15 +0100

Neoadjuvant trastuzumab should be offered to patients with human epidermal growth factor receptor 2positive locally advanced or inflammatory breast cancer alongside neoadjuvant chemotherapy, researchers report in The Lancet. (Source: MedWire News - Breast Cancer)

Herceptin Now Approved In The EU For Patients With HER2-positive Advanced Stomach Cancer

Health News from Medical News Today — Sat, 30 Jan 2010 09:00:00 +0100

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that the European Commission has approved Herceptin (trastuzumab) in combination with chemotherapy for use in patients with HER2-positive metastatic stomach (gastric) cancer. The approval is based on the impressive results from the international ToGA trial, which showed that treatment with Herceptin significantly prolongs the lives of patients with this aggressive cancer. Overall survival for patients with high levels of HER2 in the ToGA study was 16 months versus 11.8 months (on average) for patients receiving chemotherapy alone... (Source: Health News from Medical News Today)

GSK's TYKERB® Receives Accelerated Approval For First-line Combination Treatment Of Hormone Receptor Positive, HER2+/ErbB2+ Breast Cancer

Health News from Medical News Today — Sat, 30 Jan 2010 09:00:00 +0100

GlaxoSmithKline announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for a new combination regimen using TYKERB® (lapatinib) as a first-line, all-oral treatment for women with metastatic breast cancer. TYKERB is now indicated in combination with letrozole for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated... (Source: Health News from Medical News Today)

GSK's TYKERB® Receives Accelerated Approval For First-line Combination Treatment Of Hormone Receptor Positive, HER2+/ErbB2+ Breast Cancer

Breast Cancer News From Medical News Today — Sat, 30 Jan 2010 09:00:00 +0100

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Herceptin Now Approved In The EU For Patients With HER2-positive Advanced Stomach Cancer

Cancer / Oncology News From Medical News Today — Sat, 30 Jan 2010 09:00:00 +0100

GSK’s Tykerb® receives accelerated approval for first-line combination treatment of hormone receptor positive, HER2+/ErbB2+ metastatic breast cancer

GSK news — Sat, 30 Jan 2010 02:00:00 +0100

- Company progresses commitments to increase transparency (Source: GSK news)

FDA Expands Use of Approved Breast Cancer Drug

Food and Drug Administration — Fri, 29 Jan 2010 23:35:00 +0100

The U.S. Food and Drug Administration today approved Tykerb (lapatinib) in combination with Femara (letrozole) to treat hormone positive and HER2-positive advanced breast cancer in postmenopausal women for whom hormonal therapy is indicated. (Source: Food and Drug Administration)

FDA Expands Use of Approved Breast Cancer Drug

Food and Drug Administration — Fri, 29 Jan 2010 23:35:00 +0100

More Benefits of Targeting HER2 in Breast Cancer (CME/CE)

MedPage Today Hematology/Oncology — Fri, 29 Jan 2010 16:19:47 +0100

The addition of trastuzumab (Herceptin) before and after surgery significantly improved event-free survival compared with neoadjuvant chemotherapy alone in women with HER2-positive locally advanced or inflammatory breast cancer, investigators in a multicenter European trial reported. (Source: MedPage Today Hematology/Oncology)

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Metaplastic Breast Carcinoma: Clinicopathologic Features and Prognostic Value of Triple Negativity

Japanese Journal of Clinical Oncology — Fri, 29 Jan 2010 11:44:41 +0100

Conclusions In MBC, the non-triple-negative group had a poor prognosis compared with the triple-negative group, which is contrary to what has been reported in patients with invasive ductal carcinoma of breast. Further research exploring the mechanism underlying this result is needed. (Source: Japanese Journal of Clinical Oncology)

Association between gain-of-function mutations in PIK3CA and resistance to HER2-targeted agents in HER2-amplified breast cancer cell lines

Annals of Oncology — Fri, 29 Jan 2010 00:07:09 +0100

Conclusions: PIK3CA mutations are associated with resistance to HER2-targeted agents. PI3K inhibitors are potentially effective in overcoming trastuzumab resistance caused by PIK3CA mutations. S6K phosphorylation is a possibly useful pharmacodynamic marker in HER2-targeted therapy. (Source: Annals of Oncology)

[Comment] Challenging the dogma on trastuzumab: a matter of the heart

LANCET — Fri, 29 Jan 2010 00:00:00 +0100

In The Lancet today, Luca Gianni and colleagues present data from one of the largest randomised neoadjuvant trials of trastuzumab. The NOAH (NeOAdjuvant Herceptin) study is a phase 3 trial of a non-cross-resistant neoadjuvant chemotherapy regimen with trastuzumab versus chemotherapy alone in women with a locally advanced or inflammatory breast cancer that was positive for human epidermal growth factor receptor 2 (HER2, also known as ERBB2). 235 women were randomly assigned to doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil with or without 1 year of trastuzumab (delivered with chemotherapy and as monotherapy after surgery). The primary endpoint, event-free survival, was significantly improved by the addition of trastuzumab (hazard ratio 0·59, 95% CI 0·38–0·90;...

[Articles] Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort

LANCET — Fri, 29 Jan 2010 00:00:00 +0100

The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early, operable, and metastatic breast cancer that has HER2 (also known as ERBB2) overexpression or amplification. We aimed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab. (Source: LANCET)