TY - JOUR. T1 - American society of clinical oncology/college of american pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. AU - Hammond, M. Elizabeth H.. AU - Hayes, Daniel F.. AU - Dowsett, Mitch. AU - Allred, D. Craig. AU - Hagerty, Karen L.. AU - Badve, Sunil. AU - Fitzgibbons, Patrick L.. AU - Francis, Glenn. AU - Goldstein, Neil S.. AU - Hayes, Malcolm. AU - Hicks, David G.. AU - Lester, Susan. AU - Love, Richard. AU - Mangu, Pamela B.. AU - McShane, Lisa. AU - Miller, Keith. AU - Osborne, C. Kent. AU - Paik, Soonmyung. AU - Perlmutter, Jane. AU - Rhodes, Anthony. AU - Sasano, Hironobu. AU - Schwartz, Jared N.. AU - Sweep, Fred C.G.. AU - Taube, Sheila. AU - Torlakovic, Emina Emilia. AU - Valenstein, Paul. AU - Viale, Giuseppe. AU - Visscher, Daniel. AU - Wheeler, Thomas. AU - Williams, R. Bruce. AU - Wittliff, James L.. AU - Wolff, Antonio C.. PY - 2010/6/1. Y1 - 2010/6/1. N2 - Purpose: To develop a guideline to ...
Among the 629 patients, 30 (4.8%) had ALK fusions, 364 (57.9%) had EGFR mutations, and two had ALK fusions that coexisted with EGFR mutations. Intratumoral heterogeneity of ALK fusions were identified in nine patients by reverse-transcriptase polymerase chain reaction. In the two patients with an ALK/EGFR coaltered status, genetic intratumoral heterogeneity was observed both between different growth patterns and within the same growth pattern. The relative abundance of ALK and EGFR alterations was different in the same captured area. ALK fusions were positively associated with a micropapillary pattern (P = .002) and were negatively associated with a lepidic pattern (P = .008) in an expanded statistical analysis of 900 individual adenocarcinoma components, although they appeared to be more common in acinar-predominant LADCs in the analysis of 629 patients.. Conclusion ...
Introduction: The updated 2013 ASCO/CAP HER2 guidelines proposed revised scoring with the aim of capturing all patients eligible for targeted therapy. The current guidelines also address intratumoral heterogeneity using immunohistochemistry (IHC) as a platform to identify and target heterogeneously staining areas for FISH analysis. We wanted to determine if identifying the most intense areas of staining in IHC equivocal / 2+ cases would help identify genetic heterogeneity and potentially more FISH amplified patients.. Materials and Methods: Our lab offers HER2 immunohistochemistry by HercepTest™ (Dako) or 4B5 (Ventana), and dual probe FISH (Abbot Molecular or Dako IQ). We offer HER2 testing as IHC or FISH only, and also as a reflex FISH following equivocal (2+) IHC. HER2 tests performed and interpreted after 10/2013, following the implementation of the ASCO/CAP 2013 guidelines, to 5/2015 were included in this study. Both IHC and FISH were manually read following ASCO/CAP 2013 guidelines by one ...
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Silver-enhanced in-situ hybridization (SISH) is an emerging tool for the determination of the Her-2/neu amplification status in breast cancer. SISH is technically comparable to fluorescence in-situ hybridization (FISH) but does not require a fluorescence microscope for its interpretation. Although recent studies on histologic evaluations of SISH are promising, we aimed to evaluate its performance on 71 cytologic breast cancer specimens with the new combined Her-2/Chr17 probe. Her-2/neu status as routinely determined by FISH was available for all patients. We found SISH signals in cytologic cell blocks and smear specimens easy to evaluate in most cases. Small numbers of tumor cells and difficulties in identifying tumor cells in lymphocyte-rich backgrounds were limiting factors. Her-2/neu status, as determined by Her-2/Chr17 SISH, was basically identical to the results of the corresponding FISH. The discrepancies were mainly owing to the heterogeneity of Her-2/neu amplification in the tumor ...
Although cancer stemness, antitumor immunity, and intratumoral heterogeneity have all emerged as important features of cancer in recent years, their covariation across cancers has not been systematically investigated. Here we report that stemness is associated with suppressed immune response, higher intratumoral heterogeneity, and dramatically worse outcome for the majority of cancers. Although correlative analyses such as ours do not reveal causality, we propose that the stemness phenotype found in cancer cells, similar to that in normal stem cells, involves the expression of immunosuppressive factors that engender the formation of immune-privileged microenvironments in which tumor clone diversification can occur. The resulting heterogeneity may provide a substrate for the selection of treatment-resistant clones, resulting in inferior clinical outcomes. Thus, our findings implicate stemness as a shared therapeutic target to achieve the dual objectives of constraining tumor evolution and ...
Learn about PathVysion and the HER-2 DNA Probe Kit, including valuable information related to breast cancer for patients, clinicians, and laboratory professionals.
HER-2/neu expression in breast cancers (HER-2/neu phenotype and Luminal B) is associated with poor prognosis high risk breast cancers. Targeting HER-2/neu in ea...
Looking for online definition of c-erb B2/neu protein in the Medical Dictionary? c-erb B2/neu protein explanation free. What is c-erb B2/neu protein? Meaning of c-erb B2/neu protein medical term. What does c-erb B2/neu protein mean?
Methods for the detection, monitoring and treatment of malignancies in which the HER-2/neu oncogene is associated are disclosed. Detection of specific T cell activation (e.g., by measuring the proliferation of T cells) in response to in vitro exposure to the HER-2/neu protein, or detection of immunocomplexes formed between the HER-2/neu protein and antibodies in body fluid, allows the diagnosis of the presence of a malignancy in which the HER-2/neu oncogene is associated. The present invention also discloses methods and compositions, including peptides, for treating such malignancies.
Dakos HercepTest, used to predict response to Herceptin in breast cancer patients, may be the first such FDA-approved predictor of therapeutic efficacy, but it is unlikely to be the last, say Noel Weidner, MD, and Richard Zarbo, MD, DMD. How its used is going to set the stage for future similar tests.. "This is the paradigm," says Dr. Weidner. "It is the prototype for predictive testing. What happens with HER2/neu testing is likely to repeat itself.". Dr. Zarbo agrees. "We are seeing the proverbial tip of the iceberg," he declares. "This is just the start. Were going to see many more smart immunotherapies directed toward specific aspects of cancer cells. The way we handle this one will almost certainly set a precedent for future tests that are tied to therapeutics.". HER2/neu testing may be todays standard of care for metastatic breast cancer, but pathologists remain far from consensus on what test methods are most appropriate, effective, and reliably predictive. Controversies continue and ...
Compounds and compositions for eliciting or enhancing immune reactivity to HER-2/neu protein are disclosed. The compounds include polypeptides and nucleic acid molecules encoding such peptides. The co
Gene amplification is a cellular process in which multiple copies of a gene are produced. Most instances of gene amplification...
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PURPOSE: To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers. METHODS: The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance. RESULTS: Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria. RECOMMENDATIONS: The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, ...
Patient management based on HER2 status in breast carcinoma is an archetypical example of personalized medicine but remains hampered by equivocal testing and intratumoral heterogeneity. We developed a fully automated, quantitative, bright-field in situ hybridization technique (RNAscope), applied it to quantify single-cell HER2 mRNA levels in 132 invasive breast carcinomas, and compared the results with those by real-time quantitative PCR (qPCR) and Food and Drug Administration-approved methods, including fluorescence in situ hybridization (FISH), IHC, chromogenic in situ hybridization, and dual in situ hybridization. Both RNAscope and qPCR were 97.3% concordant with FISH in cases in which FISH results were unequivocal. RNAscope was superior to qPCR in cases with intratumoral heterogeneity or equivocal FISH results. This novel assay may enable ultimate HER2 status resolution as a reflex test for current testing algorithms. Quantitative in situ RNA measurement at the single-cell level may be ...
Purpose: The level of estrogen receptor (ER), progesterone receptor (PR), and HER2 aids in the determination of prognosis and treatment of breast cancer. Immunohistochemistry is currently the predominant method for assessment, but differences in methods and interpretation can substantially affect the accuracy, resulting in misclassification. Here, we investigated the association of microarray-based mRNA expression levels compared with immunohistochemistry.. Experimental Design: Microarray mRNA quantification of ER, PR, and HER2 was done by the developed TargetPrint test and compared with immunohistochemical assessment for breast tumors from 636 patients. Immunohistochemistry was done in a central laboratory and in an independent reference laboratory according to American Society of Clinical Oncology/College of American Pathologists guidelines for 100 cases. For HER2 immunohistochemistry 2+ cases, additional chromogenic in situ hybridization (CISH) was used to determine the final ...
Synonyms for gene amplification in Free Thesaurus. Antonyms for gene amplification. 46 synonyms for amplification: increase, boosting, stretching, strengthening, expansion, extension, widening, raising, heightening, deepening, lengthening.... What are synonyms for gene amplification?
Background: Gastric cancer in Kenya is ranked third in both males and females. Most patients present clinically with advanced unsusceptible disease have poor prognosis de..
With the increasing availability of agents that target individual ErbB receptors, the possible combinations incorporating these agents are numerous. This discussion will be limited to combinations employing trastuzumab and EGFR tyrosine kinase inhibitors in the treatment of HER-2-positive breast cancer. HER-2-positive metastatic breast cancer may be the best setting in which to test the concurrent inhibition of multiple ErbB receptors, because the pathogenesis and progression of the disease are driven by amplification of the HER-2/neu gene, and breast cancer patients can be selected for targeted therapy based on the presence of this molecular abnormality. Trastuzumab, the prototypical ErbB-targeted therapy, has a single agent response rate of 34% in women with metastatic HER-2/neu-positive breast cancer as measured by fluorescence in situ hybridization (47). Preclinical experiments have shown that trastuzumab has synergistic activity when combined with chemotherapeutic agents such as ...
The FDA has expanded use of a molecularly targeted therapeutic to treat certain patients with advanced or metastatic HER2-positive breast cancer.
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In all arms, study treatment begins with the first dose of trastuzumab and continues for up to 52 weeks or until the end of trastuzumab therapy.. Quality of life is assessed using the EORTC QLQ-C30 questionnaire at baseline, at 52 weeks (or at the end of trastuzumab therapy), and at 18 and 24 months (or 6 and 12 months after the completion of trastuzumab).. After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months. ...
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Overexpression of HER-2/neu seems to be associated with a survival advantage and with TNF resistance in breast, ovarian, and HER-2/neu-transfected cell lines (14-16). On the other hand, down-regulation of HER-2/neu has been shown to confer enhanced sensitivity to the cytotoxicity of TNF in doxorubicin-resistant tumor cell lines (28). Studies have additionally shown that epidermal growth factor signaling in breast and cervical carcinoma cells can also modulate the cytotoxic effects of TNF (29).. In our study, we observed that scFv23/TNF, composed of the anti-HER-2/neu single-chain antibody fused to TNF, can overcome HER-2/neu-induced TNF resistance in HER-2/neu-overexpressing SKBR-3-LP cells. The results of our study suggest that TNF-R1 expression, caspase activation, and Akt phosphorylation are three critical factors that contribute to scFv23/TNF-induced cytotoxicity in TNF-resistant HER-2/neu-overexpressing SKBR-3-LP cells.. First, a critical factor in the mediation of scFv23/TNF cytotoxicity ...
Hammond, M. E. H., Hayes, D. F., Dowsett, M., Allred, D. C., Hagerty, K. L., Badve, S., Fitzgibbons, P. L., Francis, G., Goldstein, N. S., Hayes, M., Hicks, D. G., Lester, S., Love, R., Mangu, P. B., McShane, L. M., Miller, K., Osbourne, K., Paik, S., Perlmutter, J., Rhodes, A., Sasano, H., Schwartz, J. N., Sweep, F. C., Taube, S., Torlakovic, E. E., Valenstein, P., Viale, G., Visscher, D., Wheeler, T., Williams, R. B., Whittcliff, J. L. and Wolff, A. C. (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Journal of Clinical Oncology, 28 (16). pp. 2784-2795. ISSN 0732-183X Available from: http://eprints.uwe.ac.uk/11123 Hammond, M. E. H., Hayes, D. F., Dowsett, M., Allred, D. C., Hagerty, K. L., Badve, S., Fitzgibbons, P. L., Francis, G., Goldstein, N. S., Hayes, M., Hicks, D. G., Lester, S., Love, R., Mangu, P. B., McShane, L., Miller, K., Osbourne, C. K., ...
Recently, molecular pathologic studies of intratumoral and intertumoral heterogeneity, within each individuals using multiple microdissected samples, have increased gradually (9, 10, 11, 12, 13, 14 , 20 , 33 , 34) . These studies have provided valuable insights into the process of tumorigenesis and progression in various human tumors by detecting various patterns of spatial and/or temporal differences of accumulated genetic damage within each individual. Although the concept of intratumoral heterogeneity of neoplasms appears to have been met with rather general acceptance, this area of studies in NSCLCs is still scant. Only a few studies have described a cross-sectional view of ongoing sequential genetic alterations within individual NSCLCs (12, 13, 14) . These studies have focused mainly on a comparison of genetic alterations occurring during an early stage of carcinogenesis and progression by analyzing the difference of molecular genetic alteration between premalignant or in situ lesion and ...
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A new study has revealed that a combination of chemotherapy and treatment with two drugs lengthens survival of patients with HER2-positive metastatic breast cancer.
HER-2 is a 185-kDa orphan transmembrane receptor tyrosine kinase. Dimerization of HER-2 with ligand- bound HER-3 or HER-4 receptor activates signaling pathways inside the cell. Activated HER-2 signaling stimulates cell proliferation and survival via activation of the MAPK and PI3K/Akt/mTOR pathways. Collectively these signaling pathways result in uncontrolled growth of the tumor. Several studies suggested that the overexpression/amplification of HER-2 may lead to the development and progression of pre-malignant breast disease and also tumor metastasis. Therefore, the association of HER-2 in breast cancer as well as its involvement in tumor aggressiveness makes this receptor an appropriate target for tumor-specific therapies. Several strategies have been developed to inhibit HER-2 signaling. These include a tyrosine kinase inhibitor called lapatinib and a recombinant humanized monoclonal antibody called trastuzumab (Herceptin®). In this post I will focus only on trastuzumab mediated therapy in ...
HER-2/neu is a growth factor receptor, the expression of which has been associated with a more aggressive breast tumor biology and resistance to some types of chemotherapy. Preliminary laboratory and clinical data have led to claims that HER-2/neu expression is also associated with resistance to tamoxifen. Therefore, to test the hypothesis that HER-2/neu expression is associated with a poorer response to tamoxifen, a shorter time to treatment failure (TTF), and worse survival in estrogen receptor (ER)-positive metastatic breast cancer, we examined 205 paraffin-embedded blocks of tumors from patients enrolled on Southwest Oncology Group 8228 for HER-2/neu expression. Tumors were ER positive (ER level , 3 fmol/mg cytosolic protein in either primary tumors or metastases), and patients had not received any prior therapy for metastatic disease. All patients were treated with daily tamoxifen. The study began in 1982, and median follow-up of patients who are still alive is now 9 years. Membrane ...
By doing this study, researchers hope to learn the effectiveness of the combination of Lapatinib and RAD-001 for treating patients who have progressed o
Health,Researchers Edith Perez and Edward Romond reported from two separate trials that Breast cancer patients with Her2-positive were effectively treated with Herceptin therapy using trastuzumab. //The results of their study were published in the journal The New England Journal of Medicine. The researchers compiled results from two clinical trials which compared patients getting only chemotherapy with,Trastuzumab,therapy,effective,for,Breast,cancer,patients,with,Her-2/neu,positive,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
The Young Oncologists Journal Club is an initiative from the European Society from Medical Oncology. Read the latest article on breast cancer.
Synthon today announced the initiation of the second part of its ongoing Phase I clinical trial with the investigational anti-HER2 antibody-drug conju
Additional file 1: Figure S1. of Palmitate-induced ER stress increases trastuzumab sensitivity in HER2/neu-positive breast cancer cells
The evaluation of fluorescent in situ hybridization (FISH) images is one of the most widely used methods to determine Her-2/neu status of breast samples, a
Results Digitally, 93/96 cases could be assessed (96.8%). Microscopic and digital evaluation of HER2 amplification status were concordant in 68/93 cases ((73.1%, 95% CI: 0.639 −0.823), κ 0.588). CISH underscoring was most noticeable in the amplified and equivocal categories while the highest level concordance was seen in cases with a normal copy number. Additionally there was a noticeable tendency to underestimate the average HER2 scores on WSI: lower in 59 and higher in 11 cases. There was no major difference in time spent for microscopic scoring (86.9 s) and digital scoring (81.7 s). ...
The researchers compared detection of Her2/neu in the blood between ELISA and FACTT. Her2/neu proteins were in fact first identified by the Greene laboratory in the early 1980s, and the Her2/neu gene was found by other scientists to be overexpressed in breast cancer. Her2/neu is normally a low-abundance molecule that becomes overexpressed in more than 30 percent of primary breast, ovarian, and pancreatic tumors. Part of the Her2/neu molecule is shed from the surface of tumor cells and has been detected in the blood of breast-cancer patients. Higher blood concentrations of Her2/neu correlate with a lower response rate to chemotherapy and shorter survival time after relapse ...
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TY - JOUR. T1 - Phase I study of alpelisib (BYL-719) and trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC) after trastuzumab and taxane therapy. AU - Jain, Sarika. AU - Shah, Ami N.. AU - Santa-Maria, Cesar A.. AU - Siziopikou, Kalliopi. AU - Rademaker, Alfred. AU - Helenowski, Irene. AU - Cristofanilli, Massimo. AU - Gradishar, William J.. PY - 2018/9/1. Y1 - 2018/9/1. N2 - Purpose: Activation of the phosphoinositide 3-kinase (PI3K) pathway is an important resistance mechanism to anti-HER2 therapies. This study aimed to assess the safety and activity of alpelisib (a PI3Kα isoform-specific inhibitor) with T-DM1 in trastuzumab- and taxane-resistant HER2-positive MBC. Methods: Patients with HER2-positive MBC that had progressed on trastuzumab-based therapy were treated with alpelisib daily and T-DM1 3.6 mg/kg every 3 weeks. The dose-limiting toxicity (DLT), maximum tolerated dose (MTD), adverse events, overall response rate (ORR), and clinical benefit rate (CBR = CR + ...
The high expression of metabolic enzymes, including glutaminase (GA) and lactate dehydrogenase A (LDHA), which contribute to bioenergetics and biosynthesis of mammalian cells, has been identified in a variety of cancer types. The current study indicated intratumoral heterogeneity with respect to protein expression of the metabolic enzymes in colorectal cancer (CRC). GA protein expression was determined using immunohistochemistry in 98 cases of surgically resected T3 CRC. A total of 75 cases (74%) exhibited moderate to strong immunopositivity of GA based on whole‑section examination. A significant correlation was demonstrated between GA expression and clinicopathological features, including histological type and tumor budding in a patient population. Detailed histological analysis revealed the upregulation of GA protein expression at the invasive margin, including tumor budding of CRC tissues. Semi‑quantitative examination revealed a significant difference in immunoexpression level of GA ...
To study potential sources of tumor-associated Ags in human ovarian cancer, we have established two ovarian tumor cell lines (OvS1 and OvA2) from two ovarian cancer patients, which express the cellular oncogene HER2/neu. Corresponding tumor infiltrating lymphocyte cultures have also been established and display an autologous tumor-specific pattern of cytotoxicity that is HLA-A2 restricted. To determine the potential relationship between HER2/neu expression and CTL-mediated cytolysis, we first established tumor cell clones from OvS1. These were categorized as high or low expressors of HER2/neu (cOvS1+ or cOvS1-, respectively), and cOvS1+ clones displayed a significantly higher sensitivity to CTL killing as compared with cOvS1- clones. To modulate the expression of HER2/neu, ovarian cancer cells were treated with IFN-gamma. After this exposure, HER2/neu expression was significantly decreased, whereas the expression of HLA Class I was significantly increased. Despite the increase in HLA Class I ...
The occurrence of an objective response was determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST). An objective response was defined as a complete response or a partial response as determined on 2 consecutive occasions ≥ 4 weeks apart. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions ...
Trastuzumab emtansine (T-DM1) is a novel antibodyCdrug conjugate, made up of a potent cytotoxic medication connected with a steady linker towards the anti-HER2 antibody, trastuzumab, mainly targeting chemotherapy delivery to cells overexpressing the HER2 receptor thus. of proteins is normally involved in marketing cell development through activation from the PI3K/Akt/mTOR as well as the Ras/Raf/MEK/MAPK pathways [2]. Amplification of HER2 is normally predictive of intense phenotype and poorer final result unless treated with anti-HER2 therapy Rabbit Polyclonal to BAIAP2L1. [3]. Summary of the marketplace Trastuzumab, a humanized anti-HER2 monoclonal antibody, is among the most set up gold regular treatment for HER2-amplified breasts cancer because it was first authorized by the united states FDA in 1998 [4,5]. Subsequently, two additional HER2-targeted agents have already been authorized for the treating HER2-positive metastatic breasts cancer, pertuzumab and lapatinib. Lapatanib, an dental ...