scholarly journals Weakly-Supervised Classification of HER2 Expression in Breast Cancer Haematoxylin and Eosin Stained Slides

2020 ◽  
Vol 10 (14) ◽  
pp. 4728
Author(s):  
Sara P. Oliveira ◽  
João Ribeiro Pinto ◽  
Tiago Gonçalves ◽  
Rita Canas-Marques ◽  
Maria-João Cardoso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Multiple Instance Learning ◽  
Cancer Tissue ◽  
Her2 Overexpression ◽  
Test Set ◽  
Invasive Tumour ◽  
Improved Performance ◽  
Weakly Supervised ◽  
The Individual

Human epidermal growth factor receptor 2 (HER2) evaluation commonly requires immunohistochemistry (IHC) tests on breast cancer tissue, in addition to the standard haematoxylin and eosin (H&E) staining tests. Additional costs and time spent on further testing might be avoided if HER2 overexpression could be effectively inferred from H&E stained slides, as a preliminary indication of the IHC result. In this paper, we propose the first method that aims to achieve this goal. The proposed method is based on multiple instance learning (MIL), using a convolutional neural network (CNN) that separately processes H&E stained slide tiles and outputs an IHC label. This CNN is pretrained on IHC stained slide tiles but does not use these data during inference/testing. H&E tiles are extracted from invasive tumour areas segmented with the HASHI algorithm. The individual tile labels are then combined to obtain a single label for the whole slide. The network was trained on slides from the HER2 Scoring Contest dataset (HER2SC) and tested on two disjoint subsets of slides from the HER2SC database and the TCGA-TCIA-BRCA (BRCA) collection. The proposed method attained 83.3 % classification accuracy on the HER2SC test set and 53.8 % on the BRCA test set. Although further efforts should be devoted to achieving improved performance, the obtained results are promising, suggesting that it is possible to perform HER2 overexpression classification on H&E stained tissue slides.

scholarly journals Current Approaches and Emerging Directions in HER2-resistant Breast Cancer

2014 ◽  
Vol 8 ◽  
pp. BCBCR.S9453 ◽  
Author(s):  
Adam M. Brufsky
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Initial Response ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Intrinsic Resistance ◽  
Her2 Positive

Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of breast cancers; HER2 overexpression is indicative of poor prognosis. Trastuzumab, an anti-HER2 monoclonal antibody, has led to improved outcomes in patients with HER2-positive breast cancer, including improved overall survival in adjuvant and first-line settings. However, a large proportion of patients with breast cancer have intrinsic resistance to HER2-targeted therapies, and nearly all become resistant to therapy after initial response. Elucidation of underlying mechanisms contributing to HER2 resistance has led to development of novel therapeutic strategies, including those targeting HER2 and downstream pathways, heat shock protein 90, telomerase, and vascular endothelial growth factor inhibitors. Numerous clinical trials are ongoing or completed, including phase 3 data for the mammalian target of rapamycin inhibitor everolimus in patients with HER2-resistant breast cancer. This review considers the molecular mechanisms associated with HER2 resistance and evaluates the evidence for use of evolving strategies in patients with HER2-resistant breast cancer.

scholarly journals Prognostic values of L-type amino acid transporter 1 and CD98hc expression in breast cancer

2020 ◽  
pp. jclinpath-2020-206457
Author(s):  
Masaaki Ichinoe ◽  
Tetuo Mikami ◽  
Nobuyuki Yanagisawa ◽  
Tsutomu Yoshida ◽  
Kiyomi Hana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Invasive Breast Cancer ◽  
Poor Prognosis ◽  
Growth Factor Receptor ◽  
Amino Acid Transporter ◽  
Breast Cancers ◽  
Non Invasive ◽  
Invasive Tumour ◽  
Acid Transporter

AimsL-type amino acid transporter 1 (LAT1) is a major Na+-independent neutral amino acid transporter, forming a complex with CD98hc. The aim of this study is to investigate the significance of LAT1 and CD98hc in invasive breast cancer.MethodsLAT1 and CD98hc expression was immunohistochemically assessed in 280 invasive breast cancers and analysed for association with clinicopathological features.ResultsHigh levels of LAT1 and CD98hc were observed in triple-negative breast cancers (TNBCs) possessing negative immunoreactivity with oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, compared with non-TNBCs (NTNBCs), and were associated with lymph-node metastasis and higher nuclear grade. The high-LAT1-expression group showed a poor prognosis in NTNBC and TNBC, however, high-CD98hc-expression group showed a poor prognosis only in NTNBC. LAT1 and CD98hc expression could be the prognostic factors in univariate analyses, but not in multivariate analyses. Further, we found that invasive tumour components showed higher LAT1 and CD98hc expression than non-invasive tumour components.ConclusionsLAT1 and CD98hc may possess prognostic values in invasive breast cancer. LAT1 may be linked with cancer cell activities and disease progression in breast cancer.

scholarly journals Automated Image Analysis of HER2 Fluorescence In Situ Hybridization to Refine Definitions of Genetic Heterogeneity in Breast Cancer Tissue

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Gedmante Radziuviene ◽  
Allan Rasmusson ◽  
Renaldas Augulis ◽  
Daiva Lesciute-Krilaviciene ◽  
Aida Laurinaviciene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Image Analysis ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
High Capacity ◽  
Automated Image Analysis ◽  
Cancer Tissue ◽  
Her2 Overexpression ◽  
Borderline Cases

Human epidermal growth factor receptor 2 gene- (HER2-) targeted therapy for breast cancer relies primarily on HER2 overexpression established by immunohistochemistry (IHC) with borderline cases being further tested for amplification by fluorescence in situ hybridization (FISH). Manual interpretation of HER2 FISH is based on a limited number of cells and rather complex definitions of equivocal, polysomic, and genetically heterogeneous (GH) cases. Image analysis (IA) can extract high-capacity data and potentially improve HER2 testing in borderline cases. We investigated statistically derived indicators of HER2 heterogeneity in HER2 FISH data obtained by automated IA of 50 IHC borderline (2+) cases of invasive ductal breast carcinoma. Overall, IA significantly underestimated the conventional HER2, CEP17 counts, and HER2/CEP17 ratio; however, it collected more amplified cells in some cases below the lower limit of GH definition by manual procedure. Indicators for amplification, polysomy, and bimodality were extracted by factor analysis and allowed clustering of the tumors into amplified, nonamplified, and equivocal/polysomy categories. The bimodality indicator provided independent cell diversity characteristics for all clusters. Tumors classified as bimodal only partially coincided with the conventional GH heterogeneity category. We conclude that automated high-capacity nonselective tumor cell assay can generate evidence-based HER2 intratumor heterogeneity indicators to refine GH definitions.

Immunohistochemical study of p185 HER2 and DF3 in primary breast cancer and correlation with CA-15-3 serum tumor marker

2002 ◽  
Vol 12 (1) ◽  
pp. 74-79
Author(s):  
C Dimas ◽  
M Frangos-Plemenos ◽  
E Kouskouni ◽  
A Kondis-Pafitis
Keyword(s):  
Breast Cancer ◽  
Tumor Marker ◽  
Primary Breast Cancer ◽  
Immunohistochemical Study ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Her2 Overexpression ◽  
Serum Tumor Marker ◽  
Degree Of Differentiation

Abstract.Dimas C, Frangos-Plemenos M, Kouskouni E, Kondis-Pafitis A. Immunohistochemical study of p185 HER2 and DF3 in primary breast cancer and correlation with CA-15-3 serum tumor marker.Human epidermal growth factor receptor 2 (p185 HER2) oncoprotein immunohistochemical expression and DF3 antigen distribution were evaluated in 129 patients with primary breast cancer. p185 HER2 overexpession was positively correlated with the degree of differentiation, metastatic disease, progesterone receptors, and cytoplasmic distribution of DF3 antigen. p185 HER2 overexpression had prognostic significance for the disease-free interval.

Human Epidermal Growth Factor Receptor 2 Overexpression As a Prognostic Factor in a Large Tissue Microarray Series of Node-Negative Breast Cancers

2008 ◽  
Vol 26 (35) ◽  
pp. 5697-5704 ◽  
Author(s):  
Stephen Chia ◽  
Brian Norris ◽  
Caroline Speers ◽  
Maggie Cheang ◽  
Blake Gilks ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Prognostic Factor ◽  
Growth Factor Receptor ◽  
Her2 Overexpression ◽  
Prognostic Impact ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Node Negative ◽  
Epidermal Growth

Purpose Human epidermal growth factor receptor 2 gene (HER2) is associated with a poorer outcome in node-positive breast cancer, but the results are conflicting in node-negative disease. This study assessed the prognostic impact of HER2 overexpression/amplification in a large series of node-negative breast cancers. Patients and Methods A tissue microarray (TMA) series was constructed consisting of 4,444 invasive breast cancers diagnosed in British Columbia from 1986 to 1992. Within this series, 2,026 patients were node negative, of whom 70% did not receive adjuvant systemic therapy. The TMA series was assessed for estrogen receptor (ER) and HER2. Logistic regression modeling was used to estimate odds ratios at the 10-year follow-up. Results HER2 was positive in 10.2% of the node-negative cohort. In this cohort, an inferior outcome was seen in patients with HER2-positive tumors compared with HER2-negative tumors for 10-year relapse-free survival (RFS; 65.9% v 75.5%, respectively; P = .01), distant RFS (71.2% v 81.8%, respectively; P = .004), and breast cancer–specific survival (BCSS; 75.5% v 86.3%, respectively; P = .001). A trend for a worse overall survival was also seen (P = .06). HER2 was an independent poor prognostic factor for RFS and BCSS at 10 years, with odds ratios of 1.71 (P = .01) and 2.03 (P = .003), respectively. The number of HER2-positive tumors that were ≤ 1 cm was small, but there was a trend for a worse outcome in T1b tumors. Conclusion HER2 overexpression/amplification is correlated with a poorer outcome in node-negative breast cancer. Larger studies are needed to more clearly define the prognostic impact of HER2 in tumors ≤ 1 cm, particularly within the separate hormone receptor subgroups.

scholarly journals Trastuzumab Use in Breast Cancer: Clinical Issues

2002 ◽  
Vol 9 (6) ◽  
pp. 499-507 ◽  
Author(s):  
John Horton
Keyword(s):  
Breast Cancer ◽  
Metastatic Disease ◽  
Large Scale ◽  
Cardiac Toxicity ◽  
Chemotherapeutic Agents ◽  
Cancer Tissue ◽  
Her2 Overexpression ◽  
Antitumor Effects ◽  
Large Scale Testing ◽  
Epidermal Growth

Background Overexpression of the epidermal growth factor 2 HER2 in breast cancer tissue is associated with shorter survival. Trastuzumab, a monoclonal antibody against HER2, can induce tumor responses when given alone and enhances the effectiveness of several chemotherapeutic agents. Methods The recent clinical data on outcomes regarding testing for HER2 overexpression and the tolerance, toxicity, and antitumor effects of trastuzumab are reviewed. Results Trastuzumab use is indicated either alone or with chemotherapy only in patients with IHC 3+ or FISH+ test results and survival is prolonged in patients with metastatic disease. Cardiac toxicity differs from anthracycline cardiac toxicity and is often reversible. Conclusions The safety and efficacy profile of trastuzumab in patients with metastatic disease has led to large-scale testing of addition of the intervention in the adjuvant setting.

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