MedWorm: HER2

Personalized therapy in breast cancer.

Onkologie — Mon, 06 Feb 2012 02:58:36 +0100

Authors: Marmé F, Schneeweiss A Abstract Systemic treatment of non-metastatic breast cancer is based on endocrine therapy, cytotoxic chemotherapy, and molecular targeted therapy - with the major problems of immense overtreatment of patients who would not relapse without systemic therapy and the failure of treatment in others whose disease still recurs. These deficits can only be overcome by the identification of new and better prognostic and predictive markers. Currently, adjuvant treatment stratification is based on a limited number of established factors, namely locoregional tumour stage, age, grade, expression of hormone receptors, HER2, and Ki-67. Molecular profiling techniques, however, have revolutionized our understanding of breast cancer as a heterogeneous disease. Future ...

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Recent developments and future perspectives of personalized oncology.

Onkologie — Mon, 06 Feb 2012 02:58:36 +0100

Authors: Grüllich C, von Kalle C Abstract Increasing understanding of molecular carcinogenesis has begun to change paradigms in oncology. On the diagnostic side, the characterization of key mutations and molecular pathways responsible for tumor development and progression has led to the identification of a large number of potential targets for diagnostic and therapeutic intervention. On the treatment and prevention side, molecular analysis will be of even greater importance for guiding individualized therapy. Diagnostics of molecular lesions present in each tumor will become a key feature of future clinical care. This will allow prediction of response with substantially increased accuracy, stratification of particular patient groups, and eventually personalization of therapy. Stri...

[Comment] Don't pick the loser: lessons from the GeparQuinto trial

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

In The Lancet Oncology, Michael Untch and colleagues report the first efficacy results from the GeparQuinto (GBG 44) study, a randomised phase 3 trial of lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-based and taxane-based chemotherapy. 620 women with HER2-positive operable or locally advanced breast cancer were randomly assigned to receive lapatinib (a tyrosine-kinase inhibitor of HER1 and HER2) or trastuzumab (a monoclonal antibody to the HER2 receptor), concurrent with a planned regimen of four cycles of an anthracycline (epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2) followed by four cycles of a taxane (docetaxel 100 mg/m2). (Source: The Lancet Oncology)

[Articles] Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab. Unless long-term outcome data show different results, lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy. (Source: The Lancet Oncology)

ImmunoMembrane: a publicly available web application for digital image analysis of HER2 immunohistochemistry

Histopathology — Wed, 01 Feb 2012 05:00:00 +0100

Conclusions: We anticipate that publicly available web applications, such as ImmunoMembrane, will accelerate the adoption of automated image analysis in clinical diagnostics of HER2 IHC. ImmunoMembrane is freely accessible at: http://jvsmicroscope.uta.fi/immunomembrane/. (Source: Histopathology)

HER2/HER3 Signaling Regulates NK Cell-Mediated Cytotoxicity via MHC Class I Chain-Related Molecule A and B Expression in Human Breast Cancer Cell Lines.

Journal of Immunology — Wed, 01 Feb 2012 05:00:00 +0100

In this study, we demonstrate that HER2/HER3 signaling regulates the expression of MHC class I-related chain A and B (MICA and MICB) in breast cancer cell lines. The MICA and MICB (MICA/B) molecules act as key ligands for the activating receptor NK group 2, member D (NKG2D) and promote NK cell-mediated recognition and cytolysis. Genetic silencing of HER3 but not HER2 downregulated the expression of MICA/B, and HER3 overexpression significantly enhanced MICA expression. Among the major pathways activated by HER2/HER3 signaling, the PI3K/AKT pathway was shown to predominantly regulate MICA/B expression. Treatment with the HER3-specific ligand neuregulin 1β promoted the expression in a process that was antagonized by pharmacological and genetic interference with HER3 but not by the ataxia-te...

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Comparison of ER/PR and HER2 statuses in primary and paired liver metastatic sites of breast carcinoma in patients with or without treatment

Journal of Cancer Research and Clinical Oncology — Tue, 31 Jan 2012 07:10:50 +0100

Conclusions ER/PR and HER2 statuses between primary and liver metastatic lesions of breast carcinoma can be modified after treatment but are stable in most cases during the natural metastatic process. Content Type Journal ArticleCategory Original PaperPages 1-6DOI 10.1007/s00432-012-1150-1Authors Jieqiong Liu, Department of Breast Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of ChinaHeran Deng, Department of Breast Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of ChinaWeijuan Jia, Department of Breast Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of ChinaYunjie Zeng, Department of Pathology, Sun Yat-Sen Memorial Hospital,...

Phospho-ibuprofen (MDC-917) suppresses breast cancer growth: an effect controlled by the thioredoxin system

Breast Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

Conclusions: P-I is safe and effective against breast cancer. Liposomal formulation enhances its efficacy; its effect is heavily dependent on the induction of oxidative stress and the suppression of the thioredoxin system. P-I merits further evaluation as an agent for the treatment of breast cancer. (Source: Breast Cancer Research)

Breast cancer: increasing therapy options for HER2-positive early breast cancer

Nature Clinical Practice Oncology — Tue, 31 Jan 2012 05:00:00 +0100

Nature Reviews Clinical Oncology 9, 66 (2012). doi:10.1038/nrclinonc.2011.214 Author: Nadia Harbeck Harbeck, N. Nat. Rev. Clin. Oncol.9, 10–12 (2012); doi:10.1038/nrclinonc.2011.193In the version of this article initially published online the author's name in the citation line was spelled incorrectly. The error has been corrected for the (Source: Nature Clinical Practice Oncology)

4-week vaccination regimen knocks out early breast cancer tumors, Penn researchers report

EurekAlert! - Medicine and Health — Mon, 30 Jan 2012 05:00:00 +0100

(University of Pennsylvania School of Medicine) Researchers at the Perelman School of Medicine at the University of Pennsylvania report that a short course of vaccination with an anti-HER2 dendritic cell vaccine made partly from the patient's own cells triggers a complete tumor eradication in nearly 20 percent of women with ductal carcinoma in situ, an early breast cancer. (Source: EurekAlert! - Medicine and Health)

‘Genetic heterogeneity’ in HER2/neu testing by fluorescence in situ hybridization: a study of 2522 cases

Modern Pathology AOP — Fri, 27 Jan 2012 05:00:00 +0100

‘Genetic heterogeneity’ in HER2/neu testing by fluorescence in situ hybridization: a study of 2522 cases Modern Pathology advance online publication, January 27, 2012. doi:10.1038/modpathol.2011.206 Authors: Martin C Chang, Janet I Malowany, Julita Mazurkiewicz & Martha Wood (Source: Modern Pathology AOP)

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Image Analysis of HER2 Immunohistochemical Staining: Reproducibility and Concordance With Fluorescence In Situ Hybridization of a Laboratory-Validated Scoring Technique.

American Journal of Clinical Pathology — Thu, 26 Jan 2012 22:55:27 +0100

Authors: Minot DM, Voss J, Rademacher S, Lwin T, Orsulak J, Caron B, Ketterling R, Nassar A, Chen B, Clayton A Abstract Image analysis of the HER2 immunohistochemical (IHC) stain can help determine which breast cancer patients may benefit from HER2-targeted therapy. We studied the concordance of HER2 IHC and fluorescence in situ hybridization (FISH) as well as reproducibility of surgical pathologist (SP) and cytotechnologist (CT) interpretations using manual and image analysis methodologies on 154 IHC cases. Concordances with FISH were good for IHC negative (0, 1+) cases (range, 97%-100%) and positive (3+) cases (range, 87%-100%). Image analysis had fewer equivocal (2+) results (10.4%) than CT (14.9%) and SP (16.2%) manual methods, with higher concordances to FISH (31%, 26%, and 20...

RCTs: Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer

NeLM - News — Thu, 26 Jan 2012 05:00:00 +0100

Source: N Engl J Med Area: News The efficacy of neoadjuvant chemotherapy, as measured by the rate of pathological complete response varies according to breast-cancer subtype. When anthracyclines, taxanes, and agents directed against HER2 (if indicated) are used, approximately 30 to 40% of all breast cancers that are HER2-positive or triple-negative are completely eradicated locally at the time of surgery. Long-term follow-up studies have shown a consistent correlation between pathological complete response and low rates of relapse and death among patients with these two subtypes of breast cancer. Two RCTs of neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer have been published in the New England Journal of Medicine (NEJM). The GeparQuinto phase...

Neoadjuvant Chemotherapy and Bevacizumab for HER2-Negative Breast Cancer

New England Journal of Medicine — Wed, 25 Jan 2012 22:00:13 +0100

New England Journal of Medicine, Volume 366, Issue 4, Page 299-309, January 2012. (Source: New England Journal of Medicine)

Studies Reignite Debate over Avastin in Breast Cancer (CME/CE)

MedPage Today Public Health — Wed, 25 Jan 2012 21:06:05 +0100

(MedPage Today) -- Women with HER2-negative metastatic breast cancer had significantly higher rates of pathologic complete response when bevacizumab was added to neoadjuvant chemotherapy, two large clinical trials showed. (Source: MedPage Today Public Health)

Biomarkers for antitumor activity of bevacizumab in gastric cancer models

BMC Cancer — Wed, 25 Jan 2012 05:00:00 +0100

Conclusions: VEGF levels and VEGF/bFGF ratios in tumors were related to bevacizumab sensitivity of the xenografts tested. Further clinical investigation into useful predictive markers for bevacizumab sensitivity is warranted. (Source: BMC Cancer)

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Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients

Breast Cancer Research and Treatment — Tue, 24 Jan 2012 07:35:08 +0100

Abstract Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and i...

Stromal–epithelial interactions modulate cross-talk between prolactin receptor and HER2/Neu in breast cancer

Breast Cancer Research and Treatment — Tue, 24 Jan 2012 07:35:07 +0100

In conclusion, CAFs play a critical role in bridging the cross-talk between PRL and HER2/Neu in both mouse and human models of breast cancer. The inhibitory effects of G129R on p-Neu and on tumor growth are dependent upon interactions of tumor epithelial cells with CAFs. Content Type Journal ArticleCategory Preclinical studyPages 1-13DOI 10.1007/s10549-012-1954-3Authors Cong Xu, Department of Biological Sciences, Clemson University, Clemson, SC 29634, USAJohn F. Langenheim, Department of Biological Sciences, Clemson University, Clemson, SC 29634, USAWen Y. Chen, Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA Journal Breast Cancer Research and TreatmentOnline ISSN 1573-7217Print ISSN 0167-6806 (Source: Breast Cancer Research and Treatment)

Docetaxel-containing adjuvant chemotherapy in patients with early stage breast cancer. Consistency of effect independent of nodal and biomarker status: a meta-analysis of 14 randomized clinical trials

Breast Cancer Research and Treatment — Tue, 24 Jan 2012 07:35:02 +0100

Abstract The benefit of taxanes in the adjuvant setting for node-negative (N0) early breast cancer (EBC) has not yet been established. We conducted a meta-analysis of randomized adjuvant trials comparing docetaxel-containing versus non-taxane-containing regimens. The purpose of this study was to determine whether the incorporation of docetaxel improves disease-free survival (DFS) and overall survival (OS) in early stage breast cancer. Studies were retrieved by searching major databases and the proceedings of leading breast cancer conferences. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for DFS and OS and obtained pooled estimates using an inverse-variance model. Fourteen randomized phase III studies were included (25,067 patients). The pooled HR est...

Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody–drug conjugate in development for the treatment of HER2-positive cancer

Cancer Chemotherapy and Pharmacology — Tue, 24 Jan 2012 06:48:02 +0100

Conclusions The PK profile of single-agent T-DM1 (3.6 mg/kg q3w) is predictable, well characterized, and unaffected by circulating levels of HER2 extracellular domain or residual trastuzumab. T-DM1 exposure does not correlate with clinical responses or key adverse events. Content Type Journal ArticleCategory Original ArticlePages 1-12DOI 10.1007/s00280-011-1817-3Authors Sandhya Girish, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USAManish Gupta, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USABei Wang, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USADan Lu, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USAIan E. Krop, Dana-Farber Cancer Institute, Boston, MA, USACharles L. Vogel, Sylvester Comprehensive Cancer...

Tumor markers in metastatic breast cancer subtypes: frequency of elevation and correlation with outcome

Annals of Oncology — Tue, 24 Jan 2012 05:00:00 +0100

Conclusions: TM elevation of CA 15-3, CEA and/or CA 125 was documented in the majority of patients with metastatic breast cancer with CA 15-3 occurring most commonly. Luminal subtypes expressed elevated TMs significantly more frequently compared with the non-Luminal groups. TM elevation was not different between the different sites of metastasis. Overall, elevated TMs predicted a worse BCSS. (Source: Annals of Oncology)

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New Target Therapies for Brain Metastases from Breast Cancer.

Current Cancer Drug Targets — Tue, 24 Jan 2012 05:00:00 +0100

Authors: Metro G, Fabi A Abstract Central nervous system (CNS) metastases from breast cancer (BC) represent an important cause of disease-related morbidity and mortality. For BC patients who develop CNS metastases, local control measures (both surgery and radiation) are essentially palliative and usually poorly effective, with systemic therapies often failing to achieve optimal control mainly due to the presence of the blood-brain barrier which hampers adequate penetration of therapeutic agents into the brain. However, recent evidence suggests that the status of the human epidermal growth factor receptor-2 (HER2) strongly influences the incidence of CNS metastases and the survival of BC patients from the time of development of CNS metastases, with HER2-positive (HER2+) patients gen...

Sphingosine 1-phosphate signalling in cancer.

Biochemical Society Transactions — Sun, 22 Jan 2012 22:30:00 +0100

Authors: Pyne NJ, Tonelli F, Lim KG, Long JS, Edwards J, Pyne S Abstract There is an increasing body of evidence demonstrating a critical role for the bioactive lipid S1P (sphingosine 1-phosphate) in cancer. S1P is synthesized and metabolized by a number of enzymes, including sphingosine kinase, S1P lyase and S1P phosphatases. S1P binds to cell-surface G-protein-coupled receptors (S1P1-S1P5) to elicit cell responses and can also regulate, by direct binding, a number of intracellular targets such as HDAC (histone deacetylase) 1/2 to induce epigenetic regulation. S1P is involved in cancer progression including cell transformation/oncogenesis, cell survival/apoptosis, cell migration/metastasis and tumour microenvironment neovascularization. In the present paper, we describe our resear...

Drug combination may help fight aggressive form of breast cancer

USATODAY.com Health — Sat, 21 Jan 2012 11:00:00 +0100

Combining two drugs that target an aggressive type of breast cancer known as HER2-positive appears to work better than using either drug alo ... (Source: USATODAY.com Health)

New Evidence: Dual Blockade Effective in HER2+ Breast CancerNew Evidence: Dual Blockade Effective in HER2+ Breast Cancer

Medscape Today Headlines — Fri, 20 Jan 2012 13:42:27 +0100

Lapatinib was combined with trastuzumab to treat HER2-positive breast cancer. Medscape Medical News (Source: Medscape Today Headlines)

Pharmacologic Inhibition of mTOR Improves Lapatinib Sensitivity in HER2-Overexpressing Breast Cancer Cells with Primary Trastuzumab Resistance

Fri, 20 Jan 2012 13:25:14 +0100

(Source: Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents))

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Galena Biopharma Initiates Patient Enrollment in NeuVax(TM) Phase 3 PRESENT Trial to Prevent Breast Cancer Recurrence

Medical News (via PRIMEZONE) — Fri, 20 Jan 2012 12:05:00 +0100

LAKE OSWEGO, Jan. 20, 2012 (GLOBE NEWSWIRE) -- Galena Biopharma, Inc. (Nasdaq:GALE), a biotechnology company focused on developing innovative, targeted oncology treatments, today announced the initiation of its Phase 3 PRESENT trial for NeuVax(tm) (E75 peptide plus GM-CSF) vaccine in HER2 1+ and 2+ breast cancer patients (often referred to as HER2 negative) in the adjuvant setting to prevent recurrence. (Source: Medical News (via PRIMEZONE))

Mechanistic analysis of the antitumor efficacy of human natural killer cells against breast cancer cells

Breast Cancer Research and Treatment — Fri, 20 Jan 2012 07:04:07 +0100

Abstract We investigated the role of human natural killer (NK) cells in the peripheral blood (PB) and liver in controlling breast cancer. The proportion of NK cells among liver mononuclear cells was significantly higher than among PB mononuclear cells. Liver NK cells inductively expressed higher levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) than PB NK cells in response to interleukin-2 (IL-2). Liver NK cells displayed higher cytotoxicity against various breast cancer cell lines (MDA-MB231, MDA-MB453, MDA-MB468, and MCF-7) after IL-2 stimulation than did PB NK cells. Anti-HER2 monoclonal antibody (mAb) promoted the cytotoxicity of both the types of NK cells toward HER2-expressing cell lines. All breast cancer cell lines highly expressed death-ind...

Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells.

Breast Cancer Research — Fri, 20 Jan 2012 05:00:00 +0100

Conclusion: Our data indicate that (1) a subset of primary breast cancer patients shows EMT and stem cell characteristics and (2) the currently used detection methods for CTC are not efficient to identify a subtype of CTC which underwent EMT. (3) The clinical relevance on prognosis and therapy response has to be further evaluated in a prospective trial. (Source: Breast Cancer Research)

Neoadjuvant anastrozole vs. tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): RCT

NeLM - News — Fri, 20 Jan 2012 05:00:00 +0100

Source: Lancet Oncology Area: News Aromatase inhibitors have shown increased efficacy compared with tamoxifen in postmenopausal early breast cancer. This RCT assessed the efficacy and safety of anastrozole versus tamoxifen in premenopausal women (ER-positive, HER2-negative, operable disease with WHO performance status ?2) receiving goserelin for early breast cancer in the neoadjuvant setting. The study randomised 197 patients to goserelin 3.6 mg/month plus either anastrozole 1mg per day and tamoxifen placebo (n= 98) or tamoxifen 20mg per day and anastrozole placebo (n= 99) for 24 weeks before surgery. The primary endpoint was best overall tumour response (complete response or partial response), assessed by callipers, during the 24-week neoadjuvant treatment period for the inten...

Tykerb And Herceptin - Their Role In Breast Cancer Treatment Clarified

Health News from Medical News Today — Thu, 19 Jan 2012 16:00:00 +0100

Patients with HER2-positive breast cancer have been treated with Tykerb (lapatinib) both in combination with herceptin (trastuzumab), and as an alternative single-agent therapy for pre-surgery (neo-adjuvant) chemotherapy... (Source: Health News from Medical News Today)

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Epithelial-mesenchymal transition, cancer stem cells and treatment resistance

Breast Cancer Research — Thu, 19 Jan 2012 05:00:00 +0100

Mortality from breast cancer has steadily been declining over the last decade, primarily due to earlier detection, adjuvant therapies and the advent of targeted therapies for ER positive and HER2 positive cancers [1, 2]. Despite these advances, a large number of patients relapse after an initial response to standard of care therapy. Novel therapies that prevent breast cancer relapse and metastasis are needed. An emerging hypothesis is that tumors contain a subpopulation of cells, called cancer stem cells (CSCs), which have the ability to self renew and regenerate the tumor. Increasingly, clinical evidence points to an intrinsic resistance to endocrine therapy and chemotherapy of this subpopulation of cancer stem cells [3]. The residual tumors after chemotherapy are enriched for CSCs and ha...

EGFR gene copy number increase in vulvar carcinomas is linked with poor clinical outcome

Journal of Clinical Pathology — Thu, 19 Jan 2012 05:00:00 +0100

In conclusion, EGFR copy number increases are detectable in a substantial proportion of vulvar carcinomas with relationships to advanced tumour stages and the development of lymph node metastases. EGFR copy number aberrations are connected to other gene amplifications and probably define an human papillomaviruses-independent pathway in the development of vulvar carcinomas. These data support the potential utility of EGFR inhibitors as a therapeutic alternative in a subset of vulvar carcinomas. (Source: Journal of Clinical Pathology)

Detection of HER2 and Topo 2 in breast cancers: comparison between MLPA and FISH approaches

Journal of Clinical Pathology — Thu, 19 Jan 2012 05:00:00 +0100

In conclusion, MLPA is a fast and accurate quantitative method to detect HER2 and Topo 2 amplification, and could be considered a good alternative to FISH. (Source: Journal of Clinical Pathology)

The interplay of HER2/HER3/PI3K and EGFR/HER2/PLC‐γ1 signalling in breast cancer cell migration and dissemination

The Journal of Pathology — Thu, 19 Jan 2012 05:00:00 +0100

AbstractHER2 signalling by heterodimerization with EGFR and HER3 in breast cancer is associated with worst outcome of the afflicted patients, which is not only attributed to the aggressiveness of such tumours, but also to therapy resistance. In the present study we thus investigated the role of EGFR, HER2, and HER3 lateral signalling in cell migration by applying the MDA‐MB‐468‐HER2 (MDA‐HER2) breast cancer cell line representing a valid model system. Knockdown of HER3 expression by siRNA resulted in decreased pAKT levels, abrogated EGF‐mediated PLC‐?1 activation, and a diminished EGF‐induced migratory activity depicting the interplay of EGFR/HER2/PLC‐?1 and HER2/HER3/PI3K signalling in mediating the migration of EGFR/HER2/HER3 expressing breast cancer cells. Since therapy ...

Lapatinib 'not suitable' outside clinical trials

Pharmacy Europe — Wed, 18 Jan 2012 11:47:00 +0100

Trastuzumab significantly more effective in patients with HER2-positive breast cancer, Lancet finds (Source: Pharmacy Europe)

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Researchers find discordance between standard human epidermal growth factor receptor 2 (HER2) testing and HER2 status reported on Oncotype DX

CA: A Cancer Journal for Clinicians — Wed, 18 Jan 2012 05:00:00 +0100

(Source: CA: A Cancer Journal for Clinicians)

Elucidating prognosis and biology of breast cancer arising in young women using gene expression profiling.

Clinical Cancer Research — Wed, 18 Jan 2012 05:00:00 +0100

CONCLUSIONS: Proliferation-related prognostic gene signatures can aid treatment decision-making for young women. However, breast cancer arising at a young age appears to be biologically distinct beyond subtype distribution. Separate therapeutic approaches such as targeting RANKL or mammary stem cells could be therefore needed. PMID: 22261811 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Neoadjuvant Therapy for HER2-Positive Early-Stage Breast Cancer: The Future Is Almost Here

Cancer Network — Tue, 17 Jan 2012 12:00:00 +0100

It may not be appropriate, nor always considered standard, to recommend neoadjuvant chemotherapy for all patients for whom adjuvant therapy was recommended before surgery. Indeed, tumor size and nodal status play a role, as do hormone receptors, in determining the appropriate extent of adjuvant therapy. (Source: Cancer Network)

What Is the Current Standard of Care for Anti-HER2 Neoadjuvant Therapy in Breast Cancer?

Cancer Network — Tue, 17 Jan 2012 12:00:00 +0100

This article provides a comprehensive summary of the knowledge gained from recent neoadjuvant trials conducted with agents targeting HER2, and will put them into perspective with current treatment recommendations from American and European guidelines. (Source: Cancer Network)

Improving Therapy for HER2-Positive Cancers Through Neoadjuvant Studies

Cancer Network — Tue, 17 Jan 2012 12:00:00 +0100

Treatment of HER2-positive cancers has improved rapidly over the past decade, and the pace of progress continues to accelerate. The advances have been fueled in part by the conduct of neoadjuvant studies, which have aided in the development of novel therapies and more effective combination regimens. (Source: Cancer Network)

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Preoperative Breast Cancer Treatment May Be Improved By Combining 2 Anti-HER2 Drugs

Health News from Medical News Today — Tue, 17 Jan 2012 10:00:00 +0100

Using two drugs that inhibit the growth factor HER2 for preoperative treatment of early-stage HER2-positive breast cancer appears to have better results than treatment with a single agent. In a report in the January 17 issue of The Lancet, an international research team reports that a protocol adding lapatinib (Tykerb) to trastuzumab (Herceptin) was more effective than single-drug treatment with either drug in eliminating microscopic signs of cancer at the time the tumors were surgically removed... (Source: Health News from Medical News Today)

Echocardiography signs of early cardiac impairment in patients with breast cancer and trastuzumab therapy

Clinical Research in Cardiology — Tue, 17 Jan 2012 07:17:08 +0100

Conclusion The blockade of Her2/-neu receptors with trastuzumab in patients with breast cancer led to measurable alterations of left ventricular volume, left atrial volume, and systolic function as early as 3 months after start of treatment. Content Type Journal ArticleCategory Original PaperPages 1-12DOI 10.1007/s00392-011-0406-0Authors Stefan A. Lange, Medizinische Klinik I, Kardiologie und Angiologie, Klinikum Worms, Akademisches Lehrkrankenhaus der Johannes–Gutenberg–Universität, Mainz, GermanyBernd Ebner, Herzzentrum Dresden, Universitätsklinikum Carl-Gustav-Carus an der Technischen Universität, Dresden, GermanyAstrid Wess, Medizinische Klinik I, Kardiologie und Angiologie, Klinikum Worms, Akademisches Lehrkrankenhaus der Johannes–Gutenberg–Unive...

A guide to picking the most selective kinase inhibitor tool compounds for pharmacological validation of drug targets

British Journal of Pharmacology — Tue, 17 Jan 2012 05:00:00 +0100

AbstractTo establish the druggability of a target, genetic validation needs to be supplemented with pharmacological validation. Pharmacological studies, especially in the kinase field, are hampered by the fact that many reference inhibitors are not fully selective for one target. Fortunately, the initial trickle of selective inhibitors released in the public domain has steadily swelled into a stream. However, rationally picking the most selective tool compound out of the increasing amounts of available inhibitors, has become progressively difficult due to the lack of accurate quantitative descriptors of drug selectivity. A recently published approach, termed ‘selectivity entropy’ is an improved way of expressing selectivity as a single‐value parameter and enables rank‐ordering of i...

Dual HER2 blockade with lapatinib and trastuzumab may improve response in HER2-positive early breast cancer

NeLM - News — Tue, 17 Jan 2012 05:00:00 +0100

Source: Lancet Area: News According to the results of a Phase III study published early online in the Lancet, dual inhibition of the human epidermal growth factor receptor 2 (HER2) with lapatinib and trastuzumab may improve response when used in the neoadjuvant treatment of HER2-positive breast cancer. The authors note that around 20% of breast tumours over-express the HER2 receptor, and that this is associated with a poor outcome. Trastuzumab is a humanised monoclonal antibody that targets the HER2 receptor, as does the tyrosine kinase inhibitor lapatinib; both have been shown to improve disease-free/progression-free survival in HER2-positive breast cancer. The purpose of the current study was to determine whether use of both agents together would be better than si...

Lapatinib versus trastuzumab in combination with neoadjuvant chemotherapy for HER2-positive breast cancer

NeLM - News — Tue, 17 Jan 2012 05:00:00 +0100

Source: Lancet Oncology Area: News According to the findings of a Phase III study published early online in the Lancet Oncology, trastuzumab is superior to lapatinib when used in combination with chemotherapy for the neoadjuvant treatment of HER2-positive primary breast cancer. The authors note that the tyrosine kinase inhibitor lapatinib, which targets EGFR and HER2, has been shown to improve outcomes when used in the treatment of metastatic breast cancer. The purpose of the current study was to evaluate its efficacy in the early breast cancer setting. The Phase III GeparQuinto study randomised patients with primary breast cancer to neoadjuvant therapy within three groups - the current report looks at the HER2-positive group. This included 62...

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Predictability of Adjuvant Trastuzumab Benefit in N9831 Patients Using the ASCO/CAP HER2-Positivity Criteria

JNCI — Tue, 17 Jan 2012 05:00:00 +0100

The 2007 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) joint guidelines defined criteria for HER2 positivity of tumors that modified those of the US Food and Drug Administration (FDA), causing some confusion and uncertainty among clinicians. Using data from the HER2-positive breast cancer adjuvant trial N9831, we compared eligibility for patients who met both criteria, and disease-free survival (DFS) was assessed by Cox proportional hazards regression. The number of patients in the N9831 trial retrospectively eligible for trastuzumab therapy was decreased when ASCO/CAP criteria vs FDA criteria were applied to immunohistochemistry and/or fluorescence in situ hybridization results (107 [3.7%] of 2904 patients with immunohistochemistry results, 37 [1.3%...

Ipsilateral breast tumor recurrence (IBTR) in patients with operable breast cancer who undergo breast‐conserving treatment after receiving neoadjuvant chemotherapy

Cancer — Tue, 17 Jan 2012 05:00:00 +0100

CONCLUSIONS:ER status and multifocality of the residual tumor after NAC were independent predictors of IBTR after BCT. The MDAPI was barely adaptable to the study patients in terms of predicting IBTR. Patients with ER‐positive and HER2‐negative tumors had a favorable prognosis, whereas patients who developed IBTR after NAC had significantly worse overall survival. The authors propose a new IBTR prognostic index using the 2 factors that were identified as predictive of IBTR: ER status and multifocality of the residual tumor. Cancer 2012. © 2012 American Cancer Society. (Source: Cancer)

First-line endocrine therapy alone could be a reasonable treatment option for hormone-positive, HER2-positive metastatic breast cancer.

Bulletin du Cancer — Tue, 17 Jan 2012 05:00:00 +0100

Conclusions. Our result suggests that first-line endocrine therapy is a viable therapeutic option for a selected population of metastatic breast cancer patients with HER2-positive tumors. Genomic and transcriptomic signature could help to identify tumors that remain dependant of estrogen-signaling pathway. PMID: 22257781 [PubMed - as supplied by publisher] (Source: Bulletin du Cancer)

Dual HER2 Blockade Better than One as Neoadjuvant Tx (CME/CE)

MedPage Today Hematology/Oncology — Mon, 16 Jan 2012 22:30:00 +0100

(MedPage Today) -- Significantly more women with HER2-positive breast cancer achieved complete tumor resolution when they received two targeted agents before surgery instead of one, results of a large European study showed. (Source: MedPage Today Hematology/Oncology)

A Transductionally Retargeted Adenoviral Vector for Virotherapy of Her2/neu-Expressing Prostate Cancer

Human Gene Therapy — Mon, 16 Jan 2012 16:52:42 +0100

Human Gene Therapy Jan 2012, Vol. 23, No. 1: 70-82. (Source: Human Gene Therapy)

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Combining 2 anti-HER2 drugs may provide better preoperative breast cancer treatment

EurekAlert! - Medicine and Health — Mon, 16 Jan 2012 05:00:00 +0100

(Massachusetts General Hospital) Using two drugs that inhibit the growth factor HER2 for preoperative treatment of early-stage HER2-positive breast cancer appears to have better results than treatment with a single agent. An international research team reports that a protocol adding lapatinib (Tykerb) to trastuzumab (Herceptin) was more effective than single-drug treatment with either drug in eliminating microscopic signs of cancer at the time the tumors were surgically removed. (Source: EurekAlert! - Medicine and Health)

Association of HER2/ErbB2 Expression and Gene Amplification with Pathologic Features and Prognosis in Esophageal Adenocarcinomas.

Clinical Cancer Research — Sun, 15 Jan 2012 05:00:00 +0100

CONCLUSIONS: HER2 positivity was shown in 17% of resected EACs and associated with reduced tumor aggressiveness. EACs with BE had nearly twice the odds of being HER2 positive and, within this subgroup, HER2 positivity was independently associated with improved survival. Clin Cancer Res; 18(2); 546-54. ©2012 AACR. PMID: 22252257 [PubMed - in process] (Source: Clinical Cancer Research)

Human epidermal growth factor receptor-2 gene amplification in gastric cancer using tissue microarray technology.

World Journal of Gastroenterology : WJG — Sat, 14 Jan 2012 05:00:00 +0100

CONCLUSION: In gastric cancer, HER2 amplification is the main mechanism for HER2 protein overexpression and is preserved in lymph node metastases. PMID: 22253521 [PubMed - in process] (Source: World Journal of Gastroenterology : WJG)

Phase II trial of temsirolimus in patients with metastatic breast cancer

Breast Cancer Research and Treatment — Fri, 13 Jan 2012 16:57:39 +0100

Abstract Preclinical models suggested that activating mutations of the PIK3CA gene are associated with sensitivity to inhibitors of the mammalian target of rapamycin (mTOR). In breast cancers, PIK3CA mutations are associated with estrogen receptor (ER) positivity. We therefore performed an open-label single arm phase II study of the rapamycin analog, temsirolimus, at a dose of 25 mg weekly, in women with pretreated breast cancers that were positive for ER, PR, or HER2. Archived formalin-fixed paraffin embedded tumor was collected for immunohistochemical evaluation of components of the PI3K/Akt/mTOR pathway and PIK3CA mutation analysis. Thirty-one patients were enrolled. There were no major objective responses; however, three patients had stable disease for over 24 ...

Phase I first-in-human study of TAK-285, a novel investigational dual HER2/EGFR inhibitor, in cancer patients

British Journal of Cancer AOP — Thu, 12 Jan 2012 05:00:00 +0100

Phase I first-in-human study of TAK-285, a novel investigational dual HER2/EGFR inhibitor, in cancer patients British Journal of Cancer advance online publication, January 12, 2012. doi:10.1038/bjc.2011.590 Authors: T Doi, H Takiuchi, A Ohtsu, N Fuse, M Goto, M Yoshida, N Dote, Y Kuze, F Jinno, M Fujimoto, T Takubo, N Nakayama & R Tsutsumi (Source: British Journal of Cancer AOP)

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Phase I study of lapatinib plus vinorelbine in patients with locally advanced or metastatic breast cancer overexpressing HER2

British Journal of Cancer AOP — Thu, 12 Jan 2012 05:00:00 +0100

Authors: E Brain, N Isambert, F Dalenc, V Diéras, J Bonneterre, K Rezai, M Jimenez, F Mefti-Lacheraf, E Cottura, P Tresca, L Vanlemmens, C Mahier-Aït Oukhatar, F Lokiec & P Fumoleau (Source: British Journal of Cancer AOP)

Loss of PTEN is associated with elevated EGFR and HER2 expression and worse prognosis in salivary gland cancer

British Journal of Cancer AOP — Thu, 12 Jan 2012 05:00:00 +0100

Authors: T Ettl, K Baader, C Stiegler, M Müller, A Agaimy, J Zenk, T Kühnel, M Gosau, K Zeitler, S Schwarz & G Brockhoff (Source: British Journal of Cancer AOP)

HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy.

Journal of Translational Medicine — Thu, 12 Jan 2012 05:00:00 +0100

Background: HER2 and TOP2A parameters (gene status, mRNA and protein expression) have individually been associated with the outcome of patients treated with anthracyclines. The aim of this study was to comprehensively evaluate the prognostic/predictive significance of the above parameters in early, high-risk breast cancer patients treated with epirubicin-based, dose-dense sequential adjuvant chemotherapy. Methods: In a series of 352 breast carcinoma tissues from patients that had been post-operatively treated with epirubicin-CMF with or without paclitaxel, we assessed HER2 and TOP2A gene status (chromogenic in situ hybridization), mRNA expression (quantitative reverse transcription PCR), as well as HER2 and TopoIIa protein expression (immunohistochemistry). Results: HER2 and TOP2A amplific...

The Nonreceptor-Type Tyrosine Phosphatase PTPN13 Is a Tumor Suppressor Gene in Non-Small Lung Cancer.

The American Journal of Pathology — Thu, 12 Jan 2012 05:00:00 +0100

In conclusion, the expression screening of PTPs in lung cancer reported here has identified PTPN13 as a novel candidate tumor suppressor in NSCLC whose loss increases signaling from epidermal growth factor receptor and HER2 tyrosine kinase receptors. PMID: 22245727 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)

Characteristic Genes in Luminal Subtype Breast Tumors with CD44+CD24-/Low Gene Expression Signature.

Oncology — Wed, 11 Jan 2012 05:00:00 +0100

Conclusion: This study suggests that the Notch pathway may be an important signaling pathway in luminal subtype with CD44+CD24-/low gene expression signature. In addition, either ALDH1 or SOX2 may be a candidate marker for cancer stem cells in luminal subtype breast cancer. PMID: 22237177 [PubMed - as supplied by publisher] (Source: Oncology)

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"A novel in vivo model for the study of human breast cancer metastasis using primary breast tumor-initiating cells from patient biopsies"

BMC Cancer — Tue, 10 Jan 2012 05:00:00 +0100

Conclusions: Tumorspheres isolated under defined culture conditions from patient core biopsies were tumorigenic when transplanted into the mammary fat pad of NUDE mice, and metastasized to multiple mouse organs. Micrometastases in mouse organs demonstrated a dormancy period prior to outgrowth of macrometastases. The development of macrometastases with organ-specific phenotypic distinctions provides a superior model for the investigation of organ-specific effects on metastatic cancer cell survival and growth. (Source: BMC Cancer)

Characterization and clinical evaluation of CD10+ stroma cells in the breast cancer microenvironment.

Clinical Cancer Research — Tue, 10 Jan 2012 05:00:00 +0100

CONCLUSIONS: Our results highlight the importance of CD10+ cells in breast cancer prognosis and efficacy of chemotherapy, particularly within the HER2+ breast cancer disease. PMID: 22235100 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Optical Imaging with HER2-targeted Affibody Molecules can monitor Hsp90 treatment response in a breast cancer xenograft mouse model.

Clinical Cancer Research — Tue, 10 Jan 2012 05:00:00 +0100

CONCLUSION: Optical imaging with an affibody can be used to non-invasively monitor changes in Her2 expression in vivo as a response to treatment with an Hsp90 inhibitor, with results similar to response measurements in PET imaging studies. PMID: 22235098 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Gene expression, molecular class changes and pathway analysis after neoadjuvant systemic therapy for breast cancer.

Clinical Cancer Research — Tue, 10 Jan 2012 05:00:00 +0100

CONCLUSIONS: Our data indicates that energy metabolism related processes are up-regulated and immune related signals are depleted in residual cancers. Targeting these biological processes may represent promising adjuvant treatment strategies for patients with residual cancer. PMID: 22235097 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Breast cancer: Fast, positive data from neosphere

Nature Clinical Practice Oncology — Tue, 10 Jan 2012 05:00:00 +0100

Nature Reviews Clinical Oncology 9, 67 (2012). doi:10.1038/nrclinonc.2011.205 Author: Rebecca Kirk Before the advent of HER2-targeted therapies, the 20–25% of patients with breast tumors that overexpressed HER2 had a poor prognosis. The approval and use of the HER2-targeted monoclonal antibody trastuzumab has gone some way to ameliorating this problem; however, more treatment options are still needed. (Source: Nature Clinical Practice Oncology)

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HER2-Positive Breast Cancer and Long LifeHER2-Positive Breast Cancer and Long Life

Medscape Today Headlines — Mon, 09 Jan 2012 16:25:03 +0100

Dr. Kathy Miller takes another look at CLEOPATRA and predicts that dual HER2 blockade, when offered in the adjuvant setting, will make HER2+ breast cancer a disease patients can live with, for years. Medscape Hematology-Oncology (Source: Medscape Today Headlines)

Targeted Therapies and Predictive Markers in Epithelial Malignancies of the Gastrointestinal Tract.

Archives of Pathology and Laboratory Medicine — Mon, 09 Jan 2012 05:00:00 +0100

Conclusion.-Gene testing of critical elements of the pathways targeted by these agents (such as KRAS mutational analysis in colorectal tumors and HER2/neu testing in gastric cancers) allows the ability to predict which patients will respond to these treatments. As the molecular profiling of tumors and our understanding of cancer genomics and epigenetic alterations continues to grow, it is expected that these personalized targeted therapies will form one of the mainstays of gastrointestinal cancer treatment. PMID: 22229849 [PubMed - as supplied by publisher] (Source: Archives of Pathology and Laboratory Medicine)

Verification of brain penetration of the unbound fraction of a novel HER2/EGFR dual kinase inhibitor (TAK-285) by microdialysis in rats.

Brain Research Bulletin — Mon, 09 Jan 2012 05:00:00 +0100

The objective of the present work was to verify the presence of unbound TAK-285 in the rat brain after oral administration by a microdialysis technique with simultaneous sampling of blood and brain. In a pilot microdialysis experiment no detectable amount of TAK-285 was found in the brain dialysate samples after oral administration of the drug (50mg/kg). A conventional pharmacokinetic study was performed simultaneously with the pilot microdialysis study using the same dosing suspension. TAK-285 was detected in the brain even at the last time point when the samples were taken from the animal at the end-point of the microdialysis experiment. The apparent absence of TAK-285 in blood and brain dialysate samples might be explained by a very low recovery of microdialysis probes for TAK-285 and/o...

Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer

World Journal of Surgical Oncology — Sun, 08 Jan 2012 05:00:00 +0100

Conclusions: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered. (Source: World Journal of Surgical Oncology)

Methylation of O6-methylguanine-DNA methyltransferase (MGMT) promoter gene in triple-negative breast cancer patients

Breast Cancer Research and Treatment — Sat, 07 Jan 2012 16:51:25 +0100

In conclusion, our data suggest that in TNBC with wild-type BRCA1, the direct DNA repair system may be frequently (63.6%) silenced by MGMT methylation. The evaluation of the MGMT status could offer a new adjunct in predicting tumor response to alkylating drugs in TNBC patients. Content Type Journal ArticleCategory Preclinical StudyPages 1-7DOI 10.1007/s10549-011-1945-9Authors Caterina Fumagalli, Division of Pathology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, ItalyGiancarlo Pruneri, Division of Pathology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, ItalyPaola Possanzini, Division of Pathology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, ItalyMichela Manzotti, Division of Pathology, European Institute of Oncology, Via Ri...

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Two Anti-HER2 Drugs Are Better Than OneTwo Anti-HER2 Drugs Are Better Than One

Medscape Today Headlines — Fri, 06 Jan 2012 16:20:53 +0100

Dr. Lidia Schapira looks at the striking results of the CLEOPATRA trial, which combined 2 anti-HER2-positive drugs, pertuzumab and trastuzumab, as first-line therapy in metastatic breast cancer. Medscape Hematology-Oncology (Source: Medscape Today Headlines)

Prognostic value of proliferation assay in the luminal, HER2 positive and triple negative biological classes of breast cancer

Breast Cancer Research — Fri, 06 Jan 2012 05:00:00 +0100

Conclusions: Assessment of proliferation using Ki67LI and MS can distinguish subgroups of patients within luminal/hormone receptor positive breast cancer significantly different in clinical outcomes. Overall, both Ki67LI and mitotic count scores showed comparable results. The methodology described could provide a cost effective method for prognostic sub-classification of luminal/hormone receptor positive breast cancer in routine clinical practice. (Source: Breast Cancer Research)

HER2 testing in gastric cancer: a practical approach

Modern Pathology AOP — Fri, 06 Jan 2012 05:00:00 +0100

Authors: Josef Rüschoff, Wedad Hanna, Michael Bilous, Manfred Hofmann, Robert Y Osamura, Frédérique Penault-Llorca, Marc van de Vijver & Giuseppe Viale (Source: Modern Pathology AOP)

Accuracy of HER2 status determination on breast core-needle biopsies (immunohistochemistry, FISH, CISH and SISH vs FISH)

Modern Pathology AOP — Fri, 06 Jan 2012 05:00:00 +0100

Authors: Laurent Arnould, Pascal Roger, Gaëtan MacGrogan, Marie-Pierre Chenard, André Balaton, Sophie Beauclair & Frederique Penault-Llorca (Source: Modern Pathology AOP)

CCL19 (ELC) improves TH1‐polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model

The Journal of Gene Medicine — Fri, 06 Jan 2012 05:00:00 +0100

ConclusionsCCL19 is able to induce a TH‐1 polarization of the anti Her2/neu immune response which can be further amplified by GM‐CSF. Clinical use of a pDNA(Her2/neu‐CCL19 ± GM‐CSF) vaccine might be promising in Her2/neu + breast cancer in the clinical situation of minimal residual disease. Copyright © 2012 John Wiley & Sons, Ltd. (Source: The Journal of Gene Medicine)

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Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations.

Clinical Cancer Research — Fri, 06 Jan 2012 05:00:00 +0100

CONCLUSIONS: Our findings suggest that EGFR/KRAS mutations do not occur in pure pulmonary SQCC, and occasional detection of these mutations in samples diagnosed as "SQCC" is due to challenges with the diagnosis of AD-SQC and ADC, which can be largely resolved by comprehensive pathologic assessment incorporating immunohistochemical biomarkers. PMID: 22228640 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Biological and prognostic associations of miR‐205 and let‐7b in breast cancer revealed by in situ hybridisation analysis of micro‐RNA expression in arrays of archival tumour tissue

The Journal of Pathology — Wed, 04 Jan 2012 05:00:00 +0100

AbstractMicro‐RNAs (miRNAs) are frequently dysregulated in a range of human malignancies, many have been shown to act either as tumour supressors or oncogenes, and several have been implicated in breast cancer. However, breast cancer is a diverse disease, and little is known about the relationships between miRNA expression, clinical outcome, and tumour subtype. We used locked nucleic acid probe in situ hybridisation (LNA‐ISH) to visualise, in tissue micro‐arrays (TMAs) of 2919 formalin‐fixed paraffin‐embedded (FFPE) archival breast tumours, the expression of two key miRNAs which are frequently lost in a range of solid malignancies, let‐7b and miR‐205. These miRNAs were also quantified by quantitative reverse transcription PCR in cores of FFPE tissue from 40 of these cases, de...

Triple negative breast cancer is associated with an increased risk of residual invasive carcinoma after lumpectomy

Cancer — Tue, 03 Jan 2012 05:00:00 +0100

CONCLUSION:TN subtype has a statistically significant association with an increased risk of residual tumor. This suggests the putative increase in the risk of local failure in TN patients may be related to increased residual tumor burden. Cancer 2011;. © 2011 American Cancer Society. (Source: Cancer)

Differential Influence of Dietary Soy Intake on the Risk of Breast Cancer Recurrence Related to HER2 Status.

Nutrition and Cancer — Mon, 02 Jan 2012 05:00:00 +0100

In conclusion, overall soy food intake might not affect the risk of cancer recurrence, but high intake of soy isoflavones increased the risk of cancer recurrence in HER2-positive breast cancer patients. However, further research is needed to confirm these results due to the small number of cancer recurrence events. PMID: 22211813 [PubMed - as supplied by publisher] (Source: Nutrition and Cancer)

A CpG oligodeoxynucleotide potentiates the anti-tumor effect of HSP65-Her2 fusion protein against Her2 positive B16 melanoma in mice.

International Immunopharmacology — Mon, 02 Jan 2012 05:00:00 +0100

In this study, we investigated whether a B-class CpG ODN (BW006), a TLR9 agonist, could facilitate HSP65-Her2, a recombinant protein between mycobacterial HSP65 and Her2-dervied peptide, to induce vigorous anti-tumor activity against Her2 positive tumors in mice both prophylactically and therapeutically. It was found that BW006 could enhance prophylactic and therapeutic effect of HSP65-Her2 with improved survival of the mice bearing Her2(+) B16 melanoma and HSP65-Her2 specific Th1 response. PMID: 22222115 [PubMed - as supplied by publisher] (Source: International Immunopharmacology)

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[Comment] Further progress in HER2-directed therapy

The Lancet Oncology — Sun, 01 Jan 2012 05:00:00 +0100

Outcomes for women with early stage HER2-positive breast cancer have improved markedly since the introduction of the HER2-targeted monoclonal antibody trastuzumab. Women with node-positive disease can expect relapse-free survival to exceed 80% when treated with multi-agent chemotherapy and trastuzumab. However, there is still room for improvement, both by further reducing recurrence rates and by decreasing the toxicities of treatment. For some patients, the option may ultimately exist to eliminate chemotherapy entirely. (Source: The Lancet Oncology)

[News] Trastuzumab, pertuzumab, and docetaxel: CLEOPATRA

The Lancet Oncology — Sun, 01 Jan 2012 05:00:00 +0100

Use of trastuzumab and pertuzumab—anti-HER2 monoclonal antibodies—with docetaxel as a first-line therapy prolonged survival for patients with HER2-positive metastatic breast cancer, according to a new study. (Source: The Lancet Oncology)

[Articles] Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial

The Lancet Oncology — Sun, 01 Jan 2012 05:00:00 +0100

SummaryBackgroundStudies with pertuzumab, a novel anti-HER2 antibody, show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy. We investigated the combination of pertuzumab or trastuzumab, or both, with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting.MethodsIn this multicentre, open-label, phase 2 study, treatment-naive women with HER2-positive breast cancer were randomly assigned (1:1:1:1) centrally and stratified by operable, locally advanced, and inflammatory breast cancer, and by hormone receptor expression to receive four neoadjuvant cycles of: trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m2, escalating, if tolerated, ...

Hsp90 molecular chaperone inhibitors: are we there yet?

Clinical Cancer Research — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Neckers L, Workman P Abstract Heat shock protein (Hsp) 90 is an ATP-dependent molecular chaperone that is exploited by malignant cells to support activated oncoproteins, including many cancer-associated kinases and transcription factors, and it is essential for oncogenic transformation. Originally viewed with skepticism, Hsp90 inhibitors are now being actively pursued by the pharmaceutical industry, with 17 agents having entered clinical trials. Investigators established Hsp90's druggability using the natural products geldanamycin and radicicol, which mimic the unusual ATP structure adopted in the chaperone's N-terminal nucleotide-binding pocket and cause potent and selective blockade of ATP binding/hydrolysis, inhibit chaperone function, deplete oncogenic clients, and sho...

[Modern pathologic diagnostics of breast cancer.]

Orvosi Hetilap — Sun, 01 Jan 2012 04:42:32 +0100

Authors: Szőke J, Udvarhelyi N Abstract The diagnosis of breast cancer is morphologically based. Pathologic parameters, such as tumor size, lymph node status, and histological grade are well accepted to guide treatment decisions in clinical practice. Estrogen receptor, progesterone receptor and HER2 status are also routinely assessed in today's pathology laboratories to provide further information on predictive and prognostic factors affecting patients' care. Newer molecular techniques, including gene-expression profiling have been widely used to study breast cancer and several molecular prognostic tests already available for clinical use stemmed from these scientific efforts. Authors review prognostically important aspects of the diagnostic pathology and the molecular classificat...

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Biopsy of liver metastasis for women with breast cancer: Impact on survival.

Breast — Sat, 31 Dec 2011 05:00:00 +0100

CONCLUSIONS: Liver biopsy can impact survival of patients with early metastases from BC. Discordance between primary and distant lesions can offer the patients new treatment options. PMID: 22212746 [PubMed - as supplied by publisher] (Source: Breast)

Receptor for activated C kinase 1 (RACK1): a regulator for migration and invasion in oral squamous cell carcinoma cells

Journal of Cancer Research and Clinical Oncology — Fri, 30 Dec 2011 06:49:27 +0100

Conclusion Our results clearly showed the significance of RACK1-induced OSCC cell migration, invasion and adhesion, which could explain the underlined mechanism of the effect of the gene on metastasis and clinical outcome. Also, our results confirmed its role to be a prognostic indicator and a promising drug target for OSCC cell metastasis. Content Type Journal ArticleCategory Original PaperPages 1-9DOI 10.1007/s00432-011-1097-7Authors Jing Li, State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Sec.3, Renminnan Road, Chengdu, 610041 Sichuan, ChinaYu Guo, State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Sec.3, Renminnan Road, Chengdu, 610041 Sichuan, ChinaXiaodong ...

Treml4, an Ig Superfamily Member, Mediates Presentation of Several Antigens to T Cells In Vivo, Including Protective Immunity to HER2 Protein.

Journal of Immunology — Fri, 30 Dec 2011 05:00:00 +0100

Authors: Hemmi H, Zaidi N, Wang B, Matos I, Fiorese C, Lubkin A, Zbytnuik L, Suda K, Zhang K, Noda M, Kaisho T, Steinman RM, Idoyaga J Abstract Members of the triggering expressed on myeloid cells (Trem) receptor family fine-tune inflammatory responses. We previously identified one of these receptors, called Treml4, expressed mainly in the spleen, as well as at high levels by CD8α(+) dendritic cells and macrophages. Like other Trem family members, Treml4 has an Ig-like extracellular domain and a short cytoplasmic tail that associates with the adaptor DAP12. To follow up on our initial results that Treml4-Fc fusion proteins bind necrotic cells, we generated a knockout mouse to assess the role of Treml4 in the uptake and presentation of dying cells in vivo. Loss of Treml4 expression...

Proposal for a new multidisciplinary therapeutic strategy in the breast cancer patient with sentinel lymph node metastasis.

Cirugia eEspanola — Fri, 30 Dec 2011 05:00:00 +0100

This article presents a literature review carried out by our multidisciplinary group and its strategy for avoiding routine ALND in women with SLN metastases. In this new strategy ALND should not be performed on women with T1 tumours, with 1-2 positive SLN and undergoing breast conservative surgery. On the other hand, ALND would be indicated in those patients with three or more positive SLN, presence of extracapsular invasion, mastectomised women and triple negative subtype or HER2+ tumours that have not received biological treatment with antibodies. PMID: 22209478 [PubMed - as supplied by publisher] (Source: Cirugia eEspanola)

Digital imaging in pathology – current applications and challenges

Journal of Biophotonics — Thu, 29 Dec 2011 18:48:03 +0100

This article provides an overview of current digital pathology applications and research with emphasis on whole slide imaging (WSI). Static or interactive digital pathology work stations already can be used for many purposes, e.g. telepathology expert consultations, frozen section diagnosis in remote areas, cytology screening, quality assurance, diagnostic validations for clinical trials, quantitation of hormone receptor or HER2 studies in breast cancer, or three‐dimensional visualization of anatomical structures, among others. Changes of workflow in histology laboratories are beginning to enable digital image acquisition and WSI in a routine setting. WSI plays an increasing role in pathology education, glass slide boxes in medical schools are being replaced by digital slide collections;...

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Medullary Cancer of Breast with Atypical Features – A Case Study

Journal of Pakistan Medical Students — Thu, 29 Dec 2011 05:00:00 +0100

DISCUSSION According to the World Health Organization, over 1.2 million women are diagnosed with breast cancer annually worldwide.(1) Infiltrating ductal carcinoma is a broad entity which comprises of tumors that exhibit one or more characteristics of specific types of breast cancers. There is evidence of tubular, papillary, medullary or mucinous differentiation microscopically.(2)The etiology is still unknown. Marcus et al have suggested that BRCA1-associated tumors were more likely to be of medullary or atypical medullary type.(3) For the diagnosis of medullary carcinoma to be made, strict histopathologic criteria should be completed. Traditionally, there has been no clear consensus among pathologists of the best diagnostic parameters for classifying medullary carcinoma. Since th...

Exploration of Chemical Space Based on 4-Anilinoquinazoline.

Current Medicinal Chemistry — Thu, 29 Dec 2011 05:00:00 +0100

Authors: Li DD, Hou YP, Wang W, Zhu HL Abstract Chemical space is defined as all possible small organic molecules, including those present in biological systems, which is so vast that so far only a tiny fraction of it has been explored. Indeed, a thorough examination of all "chemical space" is practically impossible. The success of three EGFR inhibitors (Gefitnib, Erlotinib, Lapatinib) suggests that 4-anilinoquinazoline scaffold is still worth developing in the future. To date hundreds of this sort of derivatives have been synthesized and show potent anticancer activities. Most of the compounds have been proved to be EGFR/HER2 kinase inhibitors, binding at the hinge region of the ATP site and some lead compounds have been optimized against a number of different kinases, including V...

Bay846, a new irreversible small molecule inhibitor of EGFR and Her2, is highly effective against malignant brain tumor models

Investigational New Drugs — Wed, 28 Dec 2011 06:53:28 +0100

Summary The epidermal growth factor receptor (EGFR) pathway is aberrantly activated in tumors and plays a key role in promoting tumor growth. Small molecule inhibitors which bind reversibly to EGFR have demonstrated limited clinical activity. Thus, there is a continued need to develop novel EGFR inhibitors with improved anti-tumor activity. Bay846 is a newly developed small molecule inhibitor that binds irreversibly to the tyrosine kinase domains of EGFR and Her2. The in vitro and in vivo efficacy of Bay846 was tested using a panel of nine human malignant brain tumor (glioma) models. Lapatinib, a reversible inhibitor of EGFR and Her2, was included for comparison. Six glioma cell lines were sensitive to Bay846 treatment. Bay846 strongly suppressed tumor cell growth in vitro ...

Association of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status with total choline concentration and tumor volume in breast cancer patients: An MRI and in vivo proton MRS study

Magnetic Resonance in Medicine — Wed, 28 Dec 2011 05:00:00 +0100

AbstractThe association of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status of breast cancer patients with total choline (tCho) concentration and tumor volume was investigated using in vivo proton magnetic resonance spectroscopy and MRI at 1.5 T. Values for tCho concentration were determined in 120 locally advanced breast cancer patients (stages IIB, IIIA, IIIB, and IIIC), 31 early breast cancer patients (stage IIA), 38 patients with benign lesions, and 37 controls. Significantly higher tCho concentration and lower tumor volume were observed in early breast cancer patients compared to locally advanced breast cancer patients (P < 0.05). tCho concentration and tumor volume did not correlate with age and menstruation. tCho cutoff values w...

Population-based outcomes after whole brain radiotherapy and re-irradiation in patients with metastatic breast cancer in the trastuzumab era

Radiation Oncology — Wed, 28 Dec 2011 05:00:00 +0100

Conclusion: The proportion of cases with HER2 positive disease was increased at repeat BRT compared to initial BRT. RPA class 1 and 2 patients should be considered for repeat BRT. (Source: Radiation Oncology)

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Development and validation of a rapid LC-MS/MS method for the determination of JCC76, a novel antitumor agent for breast cancer, in rat plasma and its application to a pharmacokinetics study.

Biomedical Chromatography : BMC — Tue, 27 Dec 2011 05:00:00 +0100

In conclusion, this rapid and sensitive method has been proven to effectively quantify JCC76 for pharmacokinetics study. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 22213194 [PubMed - as supplied by publisher] (Source: Biomedical Chromatography : BMC)

Hormone receptor and human epidermal growth factor receptor 2 status evaluation on ThinPrep specimens from breast carcinoma

Cancer Cytopathology — Sun, 25 Dec 2011 05:00:00 +0100

CONCLUSIONS:Alcohol‐based fixation seems not to affect the immunocytochemical evaluation of HR and HER2. Considering the high levels of agreement between the evaluation of HR and HER2, on both cytology specimens and on the corresponding FFPE tissue samples, the authors concluded that the TP technique can be routinely used for the biological characterization of IBC. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society. (Source: Cancer Cytopathology)

Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657)

Breast Cancer Research and Treatment — Sat, 24 Dec 2011 16:42:11 +0100

Abstract Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatu...

A phase II study of lapatinib and bevacizumab as treatment for HER2-overexpressing metastatic breast cancer

Breast Cancer Research and Treatment — Fri, 23 Dec 2011 16:52:50 +0100

Abstract Preclinical data have demonstrated that the combination of antihuman epidermal growth factor receptor-2 (anti-HER2) and antivascular endothelial growth factor (anti-VEGF)—targeted agents has antitumor activity; these data indicate certain patients with HER2-overexpressing breast cancer may derive clinical benefit from this combination. The purpose of this single-arm phase II study was to determine the efficacy and safety of the dual-targeting combination of lapatinib and bevacizumab. Women with HER2-overexpressing advanced breast cancer received 1,500 mg oral lapatinib daily plus 10 mg/kg IV bevacizumab every 2 weeks. The primary endpoint was progression-free survival (PFS) at week 12; secondary endpoints included overall tumor response rate (ORR),...

Expression of Tight Junction Molecules in Breast Carcinomas Analysed by Array PCR and Immunohistochemistry.

Pathology Oncology Research — Fri, 23 Dec 2011 05:00:00 +0100

Authors: Tőkés AM, Szász AM, Juhász E, Schaff Z, Harsányi L, Molnár IA, Baranyai Z, Besznyák I, Zaránd A, Salamon F, Kulka J Abstract In the past few decades an enormous amount of data became known to clarify the molecular composition and architecture of tight junctions (TJs). Despite the efforts, the expression and function of several TJ genes and proteins in breast carcinoma are still not known and some of the data are contradictory. The expression of forty-four TJ associated genes was examined at mRNA level in eighteen invasive ductal breast carcinoma samples and corresponding normal breast tissues by using low density array PCR. Expressions of claudins (CLDNs) 5, 10, 16, 17, and 18, and ZO-1, ZO-2 were evaluated by immunohistochemistry as well. Using immunohistochemical...

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Synthesis of a Covalent Epirubicin-(C3-amide)-Anti-HER2/neu Immunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

Cancer Biotherapy and Radiopharmaceuticals — Fri, 23 Dec 2011 04:06:44 +0100

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0. (Source: Cancer Biotherapy and Radiopharmaceuticals)

Block Copolymer Micelles Target Auger Electron Radiotherapy to the Nucleus of HER2-Positive Breast Cancer Cells.

Biomacromolecules — Thu, 22 Dec 2011 05:00:00 +0100

Authors: Hoang B, Reilly RM, Allen C Abstract Intracellular trafficking of Auger electron emitting radionuclides to perinuclear and nuclear regions of cells is critical to realizing their full therapeutic potential. In the present study, block copolymer micelles (BCMs) were labeled with the Auger electron emitter indium-111 (111In) and loaded with the radiosensitizer methotrexate. HER2 specific antibodies (trastuzumab fab) and nuclear localization signal (NLS; CGYGPKKKRKVGG) peptides were conjugated to the surface of the BCMs to direct uptake in HER2 expressing cells and subsequent localization in the cell nucleus. Cell uptake and intracellular distribution of the multifunctional BCMs were evaluated in a panel of breast cancer cell lines with different levels of HER2 expression. I...

A case of complete hydatidiform mole in a perimenopausal woman with diagnostic usefulness of p57(kip2) immunohistochemistry and HER2 fluorescent in situ hybridization.

Pathology, Research and Practice — Thu, 22 Dec 2011 05:00:00 +0100

Authors: Hatanaka K, Higashi M, Fujibayashi M, Hori S, Yoshioka T, Umekita Y, Tanimoto A Abstract Gestational trophoblastic disease in perimenopausal women is very rare. A 53-year-old perimenopausal woman complained about amenorrhea lasting over a period of 4months. Ultrasound showed enlargement of the uterus with a complex echogeneous area in the uterine cavity. Serum human chorionic gonadotropin was 67,611mIU/ml. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. The uterus contained hemorrhagic and fragile tumor with grape-like vesicles in the enlarged endometrial cavity. Microscopic examination revealed hydropically degenerated villi with circumferential hyperplasia of atypical trophoblast and cistern formation. p57(kip2) immnostaining was negative...

Drug boosts survival when breast cancer spreads to brain

Pharmacy Europe — Wed, 21 Dec 2011 10:34:00 +0100

Lapatinib more effective than herceptin for Her2-positive breast cancer patients, study finds (Source: Pharmacy Europe)

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Lapatinib boosts survival when cancer spreads to brain

Pharmacy Europe — Wed, 21 Dec 2011 10:34:00 +0100

Treatment more effective than herceptin for Her2-positive breast cancer patients, study finds (Source: Pharmacy Europe)

Breast cancer: Increasing therapy options for HER2-positive early breast cancer

Nature Clinical Practice Oncology — Wed, 21 Dec 2011 05:00:00 +0100

Nature Reviews Clinical Oncology 9, 10 (2012). doi:10.1038/nrclinonc.2011.193 Author: Nadia Harbeck One year of adjuvant trastuzumab, preferentially given upfront with a taxane as part of an anthracycline–taxane containing chemotherapy, is currently considered standard therapy for treating early-stage breast cancer. The long-awaited full publication of the BCIRG-006 trial now establishes the TCH (docetaxel, carboplatin, trastuzumab) regimen as an additional option with a distinct safety profile. (Source: Nature Clinical Practice Oncology)

Evaluation of Dual Immunohistochemistry and Chromogenic In Situ Hybridization for HER2 on a Single Section.

American Journal of Clinical Pathology — Tue, 20 Dec 2011 15:13:58 +0100

Authors: Reisenbichler ES, Horton D, Rasco M, Andea A, Hameed O Abstract The evaluation of HER2 status in invasive breast carcinoma can be performed by multiple methods. We assessed the feasibility of performing 2 of these, chromogenic in situ hybridization (CISH) and immunohistochemical staining, on single tissue sections of breast carcinoma. During assay development, sequential performance of immunohistochemical staining after CISH resulted in weaker HER2 expression than that obtained when immunohistochemical staining was performed alone; this was ameliorated by increased antibody incubation time. Performance of both techniques in a combined/hybrid protocol resulted in HER2 protein expression and gene signals identical to those produced by the individual techniques performed alon...

Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer

Annals of Oncology — Tue, 20 Dec 2011 05:00:00 +0100

Conclusions: In heavily pretreated HER2-positive MBC patients, prior exposure to T-DM1 does not exhaust the potential benefit of ongoing anti-HER2 therapy with trastuzumab- and/or lapatinib-based regimens. (Source: Annals of Oncology)

Pancreatic endocrine tumours: mutational and immunohistochemical survey of protein kinases reveals alterations in targetable kinases in cancer cell lines and rare primaries

Annals of Oncology — Tue, 20 Dec 2011 05:00:00 +0100

Conclusions: Only rare PET cases, harbouring either HER2 amplification or KIT mutation, might benefit from targeted drugs. KIT membrane expression deserves further attention as a prognostic marker. ATM mutation is involved in a proportion of PET. The finding of specific mutations in PET cell lines renders these models useful for preclinical studies involving pathway-specific therapies. (Source: Annals of Oncology)

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AVEREL: Bevacizumab in HER2+ Metastatic Breast CancerAVEREL: Bevacizumab in HER2+ Metastatic Breast Cancer

Medscape Today Headlines — Mon, 19 Dec 2011 21:57:37 +0100

Are we closer to finding a subset of patients who benefit from the addition of bevacizumab? Medscape Hematology-Oncology (Source: Medscape Today Headlines)

Efficacy of trastuzumab in Japanese patients with HER2-positive advanced gastric or gastroesophageal junction cancer: a subgroup analysis of the Trastuzumab for Gastric Cancer (ToGA) study

Gastric Cancer — Fri, 16 Dec 2011 16:54:47 +0100

Conclusions After adjusting for imbalanced patient backgrounds between arms, overall survival of Japanese patients with human epidermal growth factor 2 positive advanced/metastatic gastric or gastroesophageal junction cancer who received trastuzumab plus chemotherapy was improved compared with patients who received chemotherapy alone. Content Type Journal ArticleCategory Original articlePages 1-10DOI 10.1007/s10120-011-0118-1Authors Akira Sawaki, Department of Gastroenterology, Aichi Cancer Center Hospital, Aichi, JapanYasuo Ohashi, Department of Biostatistics, Public Health Research Foundation, Tokyo, JapanYasushi Omuro, Department of Chemotherapy, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, JapanTaroh Satoh, Department of Med...

A novel inhibitor of fatty acid synthase shows activity against HER2+ breast cancer xenografts and is active in anti-HER2 drug-resistant cell lines

Breast Cancer Research — Fri, 16 Dec 2011 05:00:00 +0100

Conclusions: G28UCM inhibits FASN activity and the growth of breast carcinoma xenografts in vivo, and is active in cells with acquired resistance to anti-HER2 drugs, which make it a candidate for further pre-clinical development. (Source: Breast Cancer Research)

Gemcitabine Plus Docetaxel Versus Docetaxel in Patients With Predominantly Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer: A Randomized, Phase III Study by the Danish Breast Cancer Cooperative Group [Breast Cancer]

Journal of Clinical Oncology — Fri, 16 Dec 2011 05:00:00 +0100

Conclusion GD compared with docetaxel demonstrated increased TTP in metastatic breast cancer. However, RR and OS were similar. Thus, the addition of gemcitabine failed to demonstrate any clinically meaningful benefit when combined with docetaxel. (Source: Journal of Clinical Oncology)

MET Amplification Identifies a Small and Aggressive Subgroup of Esophagogastric Adenocarcinoma With Evidence of Responsiveness to Crizotinib [Gastrointestinal Cancer]

Journal of Clinical Oncology — Fri, 16 Dec 2011 05:00:00 +0100

Conclusion MET amplification defines a small and aggressive subset of GEC with indications of transient sensitivity to the targeted MET inhibitor crizotinib (PF-02341066). (Source: Journal of Clinical Oncology)

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Thymic Malignancies: From Clinical Management to Targeted Therapies [REVIEW ARTICLE]

Journal of Clinical Oncology — Fri, 16 Dec 2011 05:00:00 +0100

Conclusion Drug development for the treatment of thymic malignancies is difficult because of the rarity of these tumors. Ethnic differences are becoming apparent, with aggressive subtypes being observed in Asians and African Americans. Incremental improvements in our understanding of tumor biology suggest that molecular profiling–directed therapies may be the preferred route of investigation in the future. (Source: Journal of Clinical Oncology)

Immunotherapy targeting HER2 with genetically modified T cells eliminates tumor-initiating cells in osteosarcoma

Cancer Gene Therapy — Fri, 16 Dec 2011 05:00:00 +0100

Authors: N Rainusso, V S Brawley, A Ghazi, M J Hicks, S Gottschalk, J M Rosen & N Ahmed (Source: Cancer Gene Therapy)

The prognostic significance of lymphovascular invasion in invasive breast carcinoma

Cancer — Fri, 16 Dec 2011 05:00:00 +0100

CONCLUSIONS:LVI provided a strong predictor of outcome in patients with invasive breast cancer and should be incorporated into breast cancer staging systems. Cancer 2012;. © 2011 American Cancer Society. (Source: Cancer)

Racial disparity in estrogen receptor positive breast cancer patients receiving trimodality therapy.

Breast — Fri, 16 Dec 2011 05:00:00 +0100

CONCLUSIONS: Black women had worse survival outcomes in this cohort. This disparity was driven by (1) a higher proportion of ER- and TN tumors in black women and (2) worse outcome of similarly treated black women with ER+ breast cancer. The underlying causes of racial disparity within hormone receptor categories must be further examined. PMID: 22178596 [PubMed - as supplied by publisher] (Source: Breast)

The biological features and prognosis of breast cancer diagnosed during pregnancy: A case-control study.

Acta Oncologica — Fri, 16 Dec 2011 05:00:00 +0100

Conclusions. While we did not observe any differences in tumor features, BCP patients have poorer prognosis compared to age and stage-matched control. Further studies should try to elucidate reasons for such poor outcome. PMID: 22171586 [PubMed - as supplied by publisher] (Source: Acta Oncologica)

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T cells sensitized with breast tumor progenitor cell vaccine have therapeutic activity against spontaneous HER2/neu tumors

Breast Cancer Research and Treatment — Thu, 15 Dec 2011 16:49:07 +0100

Abstract Cancer progenitor cells are critical for tumor initiation and recurrence so they are an important therapeutic target. We tested whether T cells could recognize tumor antigens expressed by breast cancer progenitor cells and acquire therapeutic activity against established metastases or delay onset of spontaneous tumors. Breast tumors were derived from HER2/neu transgenic mice and propagated in vitro under conditions that selected progenitor cells which were then used as an irradiated whole cell vaccine. A minor subset of recently sensitized T cells was isolated from vaccine-draining lymph nodes then activated in vitro to achieve numerical expansion. We show that the tumor progenitor cell vaccines reversed tolerance to a known HER2/neu epitope, otherwise inhibited by ...

Preparation of anti-HER2 monoclonal antibody-paclitaxel immunoconjugate and its biological evaluation

Journal of Huazhong University of Science and Technology -- Medical Sciences -- — Thu, 15 Dec 2011 16:45:11 +0100

Summary Anti-HER2 monoclonal antibody (Sc7301)-paclitaxel (TAX) immunoconjugate was prepared and its specific binding to tumor cells was investigated in this study. Sc7301 was conjugated to TAX by the active ester method and then the TAX-Sc7301 immunoconjugate was obtained. After purification and labeling by Cyano-fluorescein isothiocyanate (FITC), the specific binding of TAX-Sc7301 to HER2-positive tumor cells (SKOV3) and HER2-negative tumor cells (HepG2) was evaluated respectively. TAX-Sc7301 (20 nmol/L) showed distinct specific binding to SKOV3 cells rather than HepG2 cells. And the uptake of the immunoconjugate by SKOV3 cells was increased with the TAX-Sc7301 concentration (3–48 nmol/L) and the incubation time (P<0.05). It was concluded that the TAX-Sc7301 immunoco...

Systematic review and economic analysis: Lapatinib and trastuzumab in combination with an aromatase inhibitor for first-line treatment of metastatic hormone receptor

NeLM - Drug Specific Reviews — Thu, 15 Dec 2011 05:00:00 +0100

Source: Health Technology Assessment (HTA) Area: Evidence > Drug Specific Reviews This systematic review conducted by researchers with the NHS Health Technology Assessment (HTA) programme examined the clinical- and cost-effectiveness of lapatinib (LAP) in combination with an aromatase inhibitor (AI) and trastuzumab (TRA) in combination with an AI for the first-line treatment of patients who have hormone receptor-positive (HR+)/human epidermal growth factor 2-positive (HER2+) metastatic breast cancer. A search for literature was conducted until May 2010 and three trials were included in the systematic review: 1. lapatinib combined with letrozole (EGF30008 trial) 2. trastuzumab combined with anastrozole (TAnDEM trial) 3. letrozole combined with trastuzumab (eLEcTRA tr...

Double blockade of HER2 extends progression-free survival in breast cancer

Modern Medicine — Thu, 15 Dec 2011 05:00:00 +0100

Adding pertuzumab to combination therapy for women with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer prolonged progression-free survival (PFS) by a median of 6.1 months compared with combination therapy plus placebo, a study published online December 7 in the New England Journal of Medicine reports. MORE (Source: Modern Medicine)

Highly sensitive proximity mediated immunoassay reveals HER2 status conversion in the circulating tumor cells of metastatic breast cancer patients

Proteome Science — Thu, 15 Dec 2011 05:00:00 +0100

Conclusion: CEER can be multiplexed to analyze pathway proteins in a comprehensive manner with extreme specificity and sensitivity. This format is ideal for analyzing clinical samples with limited availability. (Source: Proteome Science)

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Direct comparison of 111In-labelled two-helix and three-helix Affibody molecules for in vivo molecular imaging

European Journal of Nuclear Medicine and Molecular Imaging — Wed, 14 Dec 2011 16:42:25 +0100

Conclusion For tumours with high HER2 expression, two-helix HER2-targeting Affibody molecules can provide higher tumour-to-blood ratio at the cost of lower tumour uptake. In the case of low expression, both tumour uptake and tumour-to-organ ratios are appreciably higher for three-helix than for two-helix HER2-targeting Affibody molecules. Content Type Journal ArticleCategory Original ArticlePages 1-10DOI 10.1007/s00259-011-2016-5Authors Daniel Rosik, Division of Molecular Biotechnology, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, SwedenAnna Orlova, Preclinical PET Platform, Uppsala University, Uppsala, SwedenJennie Malmberg, Preclinical PET Platform, Uppsala University, Uppsala, SwedenMohamed Altai, Unit of Biomedical Radiation Sciences, R...

A monoclonal antibody to the human HER3 receptor inhibits Neuregulin 1-beta binding and co-operates with Herceptin in inhibiting the growth of breast cancer derived cell lines

Breast Cancer Research and Treatment — Wed, 14 Dec 2011 16:42:10 +0100

Abstract The HER3 protein contributes to malignant transformation in breast and other cancer types as a consequence of elevated levels of expression, particularly in the presence of the HER2 protein. We show here that an antibody, called SGP1, to the extracellular domain of the HER3 receptor can inhibit completely Neuregulin stimulated growth of cultured breast cancer cells. Herceptin is a humanised monoclonal antibody to the HER2 protein which has an established role in the treatment of some patients with breast cancer. We demonstrate that Herceptin and SGP1 can bind simultaneously to breast cancer cells expressing both the HER2 and HER3 proteins. In the presence of moderate levels of Herceptin, addition of the SGP1 monoclonal antibody gave a dose-dependent inhibition of ...

Landscape of somatic allelic imbalances and copy number alterations in HER2-amplified breast cancer

Breast Cancer Research — Wed, 14 Dec 2011 05:00:00 +0100

IntroductionHER2-amplified breast cancer represents a clinically well-defined subgroup due to availability of targeted treatment. However, HER2-amplified tumors have been shown to be heterogeneous at the genomic level by genome-wide microarray analyses, pointing towards a need of further investigations for identification of recurrent copy number alterations and delineation of patterns of allelic imbalance. Methods: High-density whole genome array-based comparative genomic hybridisation (aCGH) and SNP array data from 260 HER2-amplified breast tumors or cell lines, and 346 HER2-negative breast cancers with molecular subtype information were assembled from different repositories. Copy number alteration (CNA), loss-of-heterozygosity (LOH), copy number neutral allelic imbalance (CNN-AI), subclo...

Classical lobular breast carcinoma consistently lacks topoisomerase‐IIα gene amplification: implications for the tailored use of anthracycline‐based chemotherapies

Histopathology — Wed, 14 Dec 2011 05:00:00 +0100

Conclusions: In the era of personalized and tailored therapies, we suggest that patients affected by the classical lobular subtype of breast carcinoma constantly lack the ad hoc predictive rationale for receiving common chemotherapy that includes anthracyclines. (Source: Histopathology)

Urinary strontium and the risk of breast cancer: A case-control study in Guangzhou, China.

Environmental Research — Wed, 14 Dec 2011 05:00:00 +0100

Authors: Chen LJ, Tang LY, He JR, Su Y, Cen YL, Yu DD, Wu BH, Lin Y, Chen WQ, Song EW, Ren ZF Abstract Strontium has been widely used in industries like electronic and pharmacy. It has a carcinogenic potential, however, and no study has been conducted to evaluate its effects on cancer risk. The aim of this study was to explore the possible association between strontium and breast cancer risk in a case-control study including 240 incident invasive breast cancer patients and 246 age-matched controls. We measured the urinary concentrations of strontium by inductively coupled plasma mass spectrometry, and conducted face-to-face interviews to obtain information on potential breast cancer risk factors. Multivariable analysis was used to estimate the association. Creatinine-adjusted level...

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Coordinated expression of oestrogen and androgen receptors in HER2-positive breast carcinomas: impact on proliferative activity

Journal of Clinical Pathology — Tue, 13 Dec 2011 05:00:00 +0100

Conclusions These results suggest that co-expression of AR and ER can provide a protective effect based on phenotypical presentation of HER2-positive carcinomas. Furthermore, lack of both steroid hormone receptors characterises the most aggressive phenotype. (Source: Journal of Clinical Pathology)

Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941

Cancer Cell — Tue, 13 Dec 2011 00:00:00 +0100

Teemu T. Junttila, Robert W. Akita, Kathryn Parsons, Carter Fields, Gail D. Lewis Phillips, Lori S. Friedman, Deepak Sampath, Mark X. Sliwkowski. (Source: Cancer Cell)

Proteins Do Not Predict Outcome of Herceptin Treatment in HER2-Positive Breast Cancer

News from Mayo Clinic — Mon, 12 Dec 2011 13:43:24 +0100

Precisely quantifying the amount of three different HER growth proteins, along with several other proteins believed linked to breast cancer, did not predict a patient's outcome after treatment for HER2-Positive Breast Cancer with Herceptin, say Mayo Clinic researchers. (Source: News from Mayo Clinic)

Mayo Clinic: Obese Patients with HER2-Positive Breast Cancer May Have Worse Outcomes

News from Mayo Clinic — Mon, 12 Dec 2011 13:34:23 +0100

SABCS: Bevacizumab Improves PFS in HER2-Positive Breast Cancer in AVEREL Study

Cancer Network — Mon, 12 Dec 2011 12:00:00 +0100

Bevacizumab (Avastin) improved progression-free survival (PFS) in women with HER2-positive locally recurrent or metastatic breast cancer by an average of 3 months when added to standard treatment as first-line therapy in the multinational, randomized, phase III AVEREL study. (Source: Cancer Network)

Addition Of Trastuzumab May Potentially Equalize Disease-Free Survival Outcomes Among Obese And Normal-Weight Patients

Health News from Medical News Today — Mon, 12 Dec 2011 08:00:00 +0100

A large, multicenter, randomized study has shown that obese patients with HER2-positive breast cancer have larger tumors, increased lymph node involvement and, when not treated with trastuzumab, poorer long-term outcomes than normal-weight patients. This is the first time the relationship between obesity and HER2-positive breast cancer has been studied, according to Jennifer A. Crozier, M.D., a medical resident at Mayo Clinic, Jacksonville, who presented the results at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011... (Source: Health News from Medical News Today)

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Conference report: Adjuvant lapatinib for early breast cancer fails in Phase III study

NeLM - News — Mon, 12 Dec 2011 05:00:00 +0100

Source: PharmaTimes, BioSpace Area: News According to a PharmaTimes report, adjuvant lapatinib failed to improve disease-free survival (DFS) for women with early-stage HER2-positive breast cancer in a Phase III study. The Phase III TEACH study was designed to evaluate the effects of lapatinib monotherapy when given to women who were diagnosed with HER2-positive breast cancer, had received treatment (but not with trastuzumab), and remained disease free. The primary objective was to compare DFS between women receiving lapatinib and those receiving placebo. Results from the study, after a median follow-up of four years, were presented at the San Antonio Breast Cancer Symposium. DFS events occurred in 13% of patients in the lapatinib arm and 17% of those in ...

Conference report: Addition of bevacizumab to trastuzumab and docetaxel results for women with HER2-positive breast cancer

NeLM - News — Mon, 12 Dec 2011 05:00:00 +0100

Source: MedPage Today Area: News Results from the AVERAL study, evaluating the addition of bevacizumab to the combination of trastuzumab and docetaxel for the first-line treatment of HER2-positive breast cancer, have been presented at the San Antonio Breast Cancer Symposium. The AVERAL study randomised 424 women with previously untreated, locally recurrent, or metastatic HER2-positive breast cancer to treatment with trastuzumab plus docetaxel, with or without bevacizumab. Treatment was continued treatment until disease progression or development of unacceptable toxicity. The primary endpoint was progression-free survival; overall survival was evaluated as a secondary endpoint. After a median follow-up of 26 months, the median PFS by investigator assessmen...

HER2 Amplification in Breast Cancer With Equivocal IHC ResultsHER2 Amplification in Breast Cancer With Equivocal IHC Results

Medscape Today Headlines — Mon, 12 Dec 2011 04:00:00 +0100

In this study, chromogenic in situ hybridization was utilized to refine results. Journal of Clinical Pathology (Source: Medscape Today Headlines)

AVEREL: Addition of Bevacizumab to First-line Trastuzumab Plus Docetaxel May Improve PFS in HER2-Positive Advanced Breast Cancer

Clinical Care Options Oncology - Breast Cancer — Sun, 11 Dec 2011 18:03:58 +0100

Capsule Summary - According to the results of the phase III AVEREL trial, addition of bevacizumab to first-line trastuzumab and docetaxel in HER2-positive advanced breast cancer may prolong PFS vs trastuzumab plus docetaxel alone, particularly in those older than 65 years of age, with measurable disease, or no previous adjuvant anti-HER2 therapy. (Source: Clinical Care Options Oncology - Breast Cancer)

Everolimus Plus Cisplatin and Paclitaxel Is Active in Heavily Pretreated Patients With Metastatic Breast Cancer

Clinical Care Options Oncology - Breast Cancer — Sun, 11 Dec 2011 17:59:48 +0100

Capsule Summary - In a single-arm phase II study, addition of everolimus to cisplatin and paclitaxel demonstrated a response in nearly 25% of patients, with the greatest benefit in those patients with HER2-positive tumors. (Source: Clinical Care Options Oncology - Breast Cancer)

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CLEOPATRA: Addition of Pertuzumab to Trastuzumab Plus Docetaxel Significantly Improves PFS in HER2-Positive Advanced Breast Cancer

Clinical Care Options Oncology - Breast Cancer — Sun, 11 Dec 2011 16:39:24 +0100

Capsule Summary - The addition of pertuzumab to trastuzumab plus docetaxel in the randomized phase III CLEOPATRA trial significantly improved survival and clinical response and was not associated with substantial additive toxicity compared with trastuzumab plus docetaxel. (Source: Clinical Care Options Oncology - Breast Cancer)

Single-Agent Neratinib Has High Antitumor Activity, but May Be Less Active Than Lapatinib/Capecitabine in Heavily Pretreated HER2-Positive Advanced Breast Cancer

Clinical Care Options Oncology - Breast Cancer — Sun, 11 Dec 2011 15:21:04 +0100

Capsule Summary - In a phase II noninferiority trial, the noninferiority of neratinib vs lapatinib/capecitabine in patients with HER2-positive advanced breast cancer was not established; however, neratinib was associated with fewer dose reductions, dose delays, and discontinuations vs lapatinib/capecitabine. (Source: Clinical Care Options Oncology - Breast Cancer)

TEACH: Delayed Adjuvant Lapatinib Did Not Significantly Improve DFS in Early-Stage HER2-Positive Breast Cancer

Clinical Care Options Oncology - Breast Cancer — Sun, 11 Dec 2011 13:27:17 +0100

Capsule Summary - Despite the lack of significant DFS benefit in the overall population, significant improvements were noted in subgroups of patients with hormone receptor–positive disease, confirmed HER2-positive disease, and those who started lapatinib within 1 year after diagnosis. (Source: Clinical Care Options Oncology - Breast Cancer)

Mayo Clinic: Obese Patients With HER2-Positive Breast Cancer May Have Worse Outcomes

Health News from Medical News Today — Sun, 11 Dec 2011 08:00:00 +0100

Obese patients with early-stage HER2-positive breast cancer may have worse outcomes than patients who are normal weight or overweight, Mayo Clinic researchers found in a study presented today at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. HER2-positive breast cancer gets its name from a protein called human epidermal growth factor receptor 2 that promotes cancer cell growth... (Source: Health News from Medical News Today)