For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
14
views
36
references
 Top references
cited by
15
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      427
      similar
       All similar
      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Relationship between HER2 gene status and selected potential biological features related to trastuzumab resistance and its influence on survival of breast cancer patients undergoing trastuzumab adjuvant treatment

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          The aim of the study was to investigate if parameters associated with human epidermal growth factor receptor type 2 ( HER2) status ( HER2 gene copy number, HER2/CEP17 ratio or polysomy of chromosome 17) are related to various biological features potentially responsible for trastuzumab resistance (PTEN, IGF-1R, MUC4, EGFR, HER3, HER4, and mutation status of PIK3CA) as well as their influence on survival of HER2-positive breast cancer patients treated with adjuvant chemotherapy and trastuzumab.

          Patients and methods

          The investigated group consisted of 117 patients with invasive ductal breast cancer (T≥1, N≥0, M0) with overexpression of HER2, who underwent radical surgery between 2007 and 2014. Status of ER, PR, and HER2 expression was retrieved from patients’ files. HER2 gene copy number was investigated by fluorescence in situ hybridization using PathVysion HER-2 DNA Probe Kit II. Expression of PTEN, IGF-1R, MUC4, EGFR, HER3, and HER4 was assessed immunohistochemically on formalin-fixed paraffin-embedded tissue sections. PIK3C mutation status was determined by qPCR analysis.

          Results

          Overexpression of HER2 protein (IHC 3+) and ER negativity corresponded to higher HER22 copy number and HER2/CEP17 ratio (.<0.001). Tumors with polysomy were characterized by higher HER22 gene copy number but lower HER2/CEP17 p ratio ( p<0.026, p<0.001). Patients with tumors featuring HER3 immunonegativity or low HER2/CEP17 ratio (#4) were characterized by 100% metastasis-free survival (.=0.018, p=0.062).

          Conclusion

          Presence of both unfavorable factors, ie, HER3 expression and high HER2/CEP17 ratio, allowed to distinguish a group of patients with worse prognosis (.=0.001).

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: not found

          HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues.

          Marilyn A. Owens, Bruce Horten, Moacyr M Da Silva (2004)
          To analyze HER2 amplification in a large cohort of diagnostic breast cancer specimens, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed on the same specimens with use of Food and Drug Administration&approved products. Procedures were standardized following the manufacturers' recommendations. Of 116,736 IHC specimens, 20% were positive for HER2. In 16,092 FISH specimens, 22.7% showed HER2 amplification. In the subset of 6556 tissues analyzed with IHC and FISH, however, 59% were positive on IHC and 23.6% were amplified on FISH. The increased frequency of positive test results is skewed by more frequent reflex FISH testing. In general, expression and amplification trended together, with the least amplification (4.1%) seen in IHC-negative cases, 7.4% amplification seen in IHC 1+ cases, 23.3% amplification seen in IHC 2+ cases, and 91.7% amplification seen in IHC 3+ cases. When FISH amplification ratios were stratified, the low FISH ratios (2.0-2.2) were most frequently seen in specimens with negative IHC results, high ratios (>5.0) were seen in IHC 3+ specimens, and intermediate levels of amplification were similar for all levels of IHC. The effect of changing the cutoff point was analyzed: removing cases with a ratio of exactly 2.0 decreased the FISH positivity rate to 22.2% in the combined IHC and FISH cohort. Sequentially moving the cutoff point to 2.2 and 2.5 affected cases at all IHC expression levels. Each change removed approximately 2% from the apparent positivity. This large database provides the distribution frequency of HER2 protein expression and gene amplification in invasive ductal and lobular breast cancer. The relationship between level of HER2 amplification and clinical outcome will require reanalysis of pivotal trial data.
          Article 0 comments Cited 171 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer.

            G Konecny, G Pauletti, M Pegram … (2003)
            HER-2/neu, which encodes a receptor tyrosine kinase, is amplified and overexpressed in 20%-25% of human breast cancers. Such tumors are often resistant to hormone therapy. Despite a general inverse association between HER-2/neu amplification/overexpression and estrogen receptor (ER) and/or progesterone receptor (PR) expression, a fraction of patients are both HER-2/neu- and hormone receptor (HR)-positive. The efficacy of hormone therapy in this group is currently a matter of debate. To better understand the relationship between HER-2/neu positivity and HR expression, we analyzed HER-2/neu, ER, and PR as continuous variables in breast cancer cell lines and two cohorts of primary breast cancer patients. HER-2/neu and ER/PR expression was analyzed by enzyme-linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA), respectively, in 14 human breast cancer cell lines, some of which had been transfected with the HER-2/neu gene. For the clinical study population, HER-2/neu protein levels were assessed by ELISA (cohort A, n = 665), and HER-2/neu gene copy number was determined using fluorescence in situ hybridization (cohort B, n = 894). ER/PR expression was analyzed by EIA (cohort A) or radioligand binding (cohort B). Associations between HER-2/neu and ER/PR expression were analyzed using Spearman's rho correlation and the chi-square test, and absolute levels were compared using the Mann-Whitney U test. All statistical tests were two-sided. HR-positive human breast cancer cell lines transfected with the HER-2/neu gene expressed statistically significantly lower levels of ER and PR than parental lines. In the clinical cohorts, levels of HER-2/neu overexpression and gene amplification were inversely correlated with ER/PR levels (Cohort A [n = 112]: for ER, r = -0.34, P<.001; for PR, r = -0.24, P =.010. Cohort B [n = 188]: for ER, r = -0.39, P<.001; for PR, r = -0.26, P<.001). Among patients with HR-positive tumors, HER-2/neu-positive tumors had statistically significantly lower ER/PR levels than HER-2/neu-negative ones (Cohort A: for ER, median = 25 fmol/mg [interquartile range [IQR] = 13-78] versus median = 38.5 fmol/mg [IQR = 17-99] and P =.031; for PR, median = 35 fmol/mg [IQR = 12-119] versus median = 88.5 fmol/mg [IQR = 22-236] and P<.001. Cohort B: for ER, median = 44 fmol/mg [IQR = 13-156] versus median = 92 fmol/mg [IQR = 35-235] and P<.001; for PR, median = 36 fmol/mg [IQR = 13-108] versus median = 84 fmol/mg [IQR = 24-250] and P<.001). Patients with higher levels of HER-2/neu overexpression or amplification had statistically significantly lower levels of ER/PR than patients with lower levels of HER-2/neu overexpression or amplification. Because absolute HR levels are strongly related to response to hormone therapy in primary and advanced breast cancer, reduced ER/PR expression may be one mechanism to explain the relative resistance of HER-2/neu-positive:HR-positive tumors to hormone therapy.
            Article 0 comments Cited 94 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              HER3 overexpression and survival in solid tumors: a meta-analysis.

              Alberto Ocana, Francisco Vera-Badillo, Bostjan Seruga … (2013)
              The human epidermal growth factor receptor 3 (HER3) is an ErbB/HER family member that dimerizes with other ErbB receptors such as HER2. Numerous agents against HER3 are in clinical development despite variable data for the prognostic impact of HER3 expression. Here we report a meta-analysis of the association of HER3 expression and survival in solid tumors. PubMed was searched for studies evaluating expression of HER3 (as measured by immunohistochemistry) and overall survival (OS) in solid tumors. Published data were extracted and computed into odds ratios (ORs) for death at 3 and 5 years. Data were pooled using the Mantel-Haenszel random-effect model. All statistical tests were two-sided. Analysis included 12 studies: three that evaluated colorectal cancer, two that evaluated gastric cancer, two that evaluated breast cancer, and one each that evaluated melanoma, ovarian cancer, head and neck cancer, pancreatic cancer, and cervical cancer. The median percentage of cancers with HER3 overexpression was 42.2%. HER3 was associated with worse OS at both 3 years (OR = 2.24, 95% confidence interval [CI] = 1.77 to 2.83, P < .001) and 5 years (OR = 2.20, 95% CI = 1.75 to 2.76, P < .001). Among studies with common HER2 overexpression (breast, gastric, and ovarian cancers), the magnitude of effect of HER3 on OS was statistically significantly greater for both 3-year OS (OR = 3.12, 95% CI = 2.24 to 4.37) and 5-year OS (OR = 2.84, 95% CI = 2.09 to 3.88). Expression of HER3 is associated with worse survival in solid tumors. The influence of HER3 may be greater in those tumors where HER2 is commonly overexpressed.
              Article 0 comments Cited 93 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): OncoTargets and Therapy
                Title: OncoTargets and therapy
                Publisher: Dove Medical Press
                ISSN (Electronic): 1178-6930
                Publication date Collection: 2018
                Publication date (Electronic): 03 August 2018
                Volume: 11
                Pages: 4525-4535
                Affiliations
                [1 ]Department of Tumour Pathology, z5adamcz@ 123456cyfronet.pl
                [2 ]Department of Systemic and Generalized Malignancies, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Cracow Branch, Cracow, Poland
                Author notes
                Correspondence: Agnieszka Adamczyk, Department of Tumour Pathology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Cracow, Poland, Cracow Branch, ul. Garncarska 11, Cracow 31-115, Poland, Tel +48 12 63 48 415, Fax +48 12 423 1076, Email z5adamcz@ 123456cyfronet.pl
                Article
                Publisher ID: ott-11-4525
                DOI: 10.2147/OTT.S166983
                PMC ID: 6082350
                PubMed ID: 30122944
                SO-VID: 1a21d6c3-5051-4ac6-be4d-986629bec1d5
                Copyright © © 2018 Adamczyk et al. This work is published and licensed by Dove Medical Press Limited
                License:

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: her2-overexpressing breast cancer,her2 amplification,her2 gene copy number,her2/cep17 ratio,her3 expression,trastuzumab
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: her2-overexpressing breast cancer, her2 amplification, her2 gene copy number, her2/cep17 ratio, her3 expression, trastuzumab

                Comments

                Comment on this article

                scite_

                Similar content427

                See all similar

                Cited by15

                See all cited by

                Most referenced authors939

                See all reference authors