A clinical evaluation of the TK 210 ELISA in sera from breast cancer patients demonstrates high sensitivity and specificity in all stages of disease

BACKGROUND: Accurate assessment of HER-2 is imperative in selecting patients for targeted therapy. Most commonly used test methods for HER-2 are immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). We evaluated the concordance between FISH and IHC for HER-2 in breast cancer samples using Food and Drug Administration approved tests.MATERIAL AND METHODS: Archived paraffin tissue blocks from 73 breast cancer patients were used. HER-2 immunostaining was performed using Ventana anti–HER-2 monoclonal antibody. The FISH assay was performed using PathVysion™ HER-2 DNA Probe Kit.RESULTS: Of the 73 cases 68.5% were IHC 0/1+, 15.07% were IHC 2+ and 16.44% were IHC 3+. Successful hybridisation was achieved in 72 cases. HER-2 FISH amplification was determined in 16.67% cases. Ten IHC 3+ and two IHC 2+ cases were FISH positive. Two of the IHC 3+ cases were FISH negative. Concordance rate was 100%, 18.18% and 83.33% for IHC 0/1+, 2+ and 3+ group, respectively. Total concordance was 84.72%, kappa 0.598 (p < 0.0001). The sensitivity of IHC in detecting IHC 2+ and IHC 3+ cases was 16.7% and 83.3%, and the specificity was 85% and 96.67%, respectively.CONCLUSION: The consistency between the methods was highest for IHC negative and lowest for IHC equivocal cases. The immunohistochemistry showed high sensitivity for IHC 2+/3+ cases and high specificity for IHC 3+ cases. Our results support the view that false-positive rather than false-negative IHC results are a problem with HER-2/IHC testing, and that IHC should be used as an initial screening test, but IHC 2+/ 3+ results should be confirmed by FISH.

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Aquaporin 1 promotes sensitivity of anthracycline chemotherapy in breast cancer by inhibiting β-catenin degradation to enhance TopoIIα activity

Cell Death and Differentiation ◽

10.1038/s41418-020-00607-9 ◽

2020 ◽

Vol 28 (1) ◽

pp. 382-400

Author(s):

Wei Chong ◽

Huikun Zhang ◽

Zhifang Guo ◽

Limin Yang ◽

Ying Shao ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Nuclear Translocation ◽

Glycogen Synthase ◽

Breast Cancer Mortality ◽

High Sensitivity ◽

Breast Cancer Patients ◽

Chemotherapy Drugs ◽

Aqp1 Expression ◽

Anthracycline Chemotherapy

AbstractAnthracyclines are a class of conventional and commonly used frontline chemotherapy drugs to treat breast cancer. However, the anthracycline-based regimens can only reduce breast cancer mortality by 20–30%. Furthermore, there is no appropriate biomarker for predicting responses to this kind of chemotherapy currently. Here we report our findings that may fill this gap by showing the AQP1 (Aquaporin1) protein as a potential response predictor in the anthracycline chemotherapy. We showed that breast cancer patients with a high level of AQP1 expression who underwent the anthracycline treatment had a better clinical outcome relative to those with a low level of AQP1 expression. In the exploration of the underlying mechanisms, we found that the AQP1 and glycogen synthase kinase-3β (GSK3β) competitively interacted with the 12 armadillo repeats of β-catenin, followed by the inhibition of the β-catenin degradation that led to β-catenin’s accumulation in the cytoplasm and nuclear translocation. The nuclear β-catenin interacted with TopoIIα and enhanced TopoIIα’s activity, which resulted in a high sensitivity of breast cancer cells to anthracyclines. We also found, the miR-320a-3p can attenuate the anthracycline’s chemosensitivity by inhibiting the AQP1 expression. Taken together, our findings suggest the efficacy of AQP1 as a response predictor in the anthracycline chemotherapy. The application of our study includes, but is not limited to, facilitating screening of the most appropriate breast cancer patients (who have a high AQP1 expression) for better anthracycline chemotherapy and improved prognosis purposes.

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Prognosis of Treatment Response (Pathological Complete Response) in Breast Cancer

Biomarker Insights ◽

10.4137/bmi.s9387 ◽

2012 ◽

Vol 7 ◽

pp. BMI.S9387 ◽

Cited By ~ 5

Author(s):

Jason B. Nikas ◽

Walter C. Low ◽

Paul A. Burgio

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Sensitivity And Specificity ◽

Pathological Complete Response ◽

Prognostic Biomarker ◽

Complete Response ◽

Mathematical Function ◽

Breast Cancer Patients ◽

Model Complex ◽

Clinical Stages

Pertaining to the female population in the USA, breast cancer is the leading cancer in terms of annual incidence rate and, in terms of mortality, the second most lethal cancer. There are currently no biomarkers available that can predict which breast cancer patients will respond to chemotherapy with both sensitivity and specificity > 80%, as mandated by the latest FDA requirements. In this study, we have developed a prognostic biomarker model (complex mathematical function) that–-based on global gene expression analysis of tumor tissue collected during biopsy and prior to the commencement of chemotherapy–-can identify with a high accuracy those patients with breast cancer (clinical stages I–III) who will respond to the paclitaxel-fluorouracil-doxorubicin-cyclophosphamide chemotherapy and will experience pathological complete response (Responders), as well as those breast cancer patients (clinical stages I–III) who will not do so (Non-Responders). Most importantly, both the application and the accuracy of our breast cancer prognostic biomarker model are independent of the status of the hormone receptors ER, PR, and HER2, as well as of the ethnicity and age of the subjects. We developed our prognostic biomarker model with 50 subjects [10 responders (R) and 40 non-responders (NR)], and we validated it with 43 unknown (new and different) subjects [10 responders (R) and 33 non-responders (NR)]. All 93 subjects were recruited at five different clinical centers around the world. The overall sensitivity and specificity of our prognostic biomarker model were 90.0% and 91.8%, respectively. The nine most significant genes identified, which comprise the input variables to the mathematical function, are involved in regulation of transcription; cell proliferation, invasion, and migration; oncogenesis; suppression of immune response; and drug resistance and cancer recurrence.

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Endocrinological and clinical evaluation of two depot formulations of leuprolide acetate in pre- and perimenopausal breast cancer patients

Cancer Chemotherapy and Pharmacology ◽

10.1007/s002800050924 ◽

1999 ◽

Vol 43 (6) ◽

pp. 461-466 ◽

Cited By ~ 8

Author(s):

Francesco Boccardo ◽

Alessandra Rubagotti ◽

Domenico Amoroso ◽

Biagio Agostara ◽

Dino Amadori ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Clinical Evaluation ◽

Leuprolide Acetate ◽

Breast Cancer Patients

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Diagnostic usefulness of serum carcinoembryonic antigen determinations in breast cancer patients

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2003.3552 ◽

2003 ◽

Vol 3 (2) ◽

pp. 30-34

Author(s):

Zlata Mujagić ◽

Hamza Mujagić

Keyword(s):

Breast Cancer ◽

Carcinoembryonic Antigen ◽

Cancer Patients ◽

Sensitivity And Specificity ◽

Tumour Marker ◽

Breast Cancer Patients ◽

Female Patients ◽

Healthy Women ◽

Serum Carcinoembryonic Antigen ◽

Circulating Levels

Background and purpose: Carcinoembryonic antigen (CEA) is used as a tumour marker in breast cancer (BC). In order to assess diagnostic value of CEA in BC we examined its serum levels and frequencies of its increase in breast cancer patients (BCP), and compared them to those in controls. We also determined CEA in patients with metastatic and non-metastatic BC, and calculated sensitivity and specificity of CEA in BC.Patients and methods: The main experimental group consisted of 47 female patients with histologically proved diagnosis of BC. There were two control groups: clinically healthy women, and female patients with other locations of cancer. Circulating levels of CEA were measured by means of immunoradiometric assay. Results were processed by means of t-test and two-way analysis of variance.Results: Circulating levels of CEA, before treatment in BCP, were significantly higher (p<0.0001) than in healthy women, and in patients with other cancers (p<0.007), while serum CEA in other cancer patients was significantly higher (p<0.01) than in healthy control. There was a difference between frequencies of CEA increase in BCP and healthy women, while such a difference did not exist between BCP and other cancer patients. The circulating levels of CEA in metastatic BCP were significantly higher (p<0.03) in comparison to non-metastatic patients. Sensitivity and specificity of CEA in BCP was 65.0%, and 57.1%, respectively.Conclusions: CEA does not have high tumour specificity for BC, since its circulating levels as well as frequencies of its increase may be elevated in patients with other types and locations of cancer, different from breast cancer. CEA can be detected in the serum of majority of patients with metastatic BC. CEA may be used as prognostic tumour marker in advanced BC.

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A new enrichment model for high sensitivity detection and downstream analyses of circulating tumor cells in breast cancer patients.

10.1158/0008-5472.sabcs-4162 ◽

2009 ◽

Author(s):

G Deng ◽

M Mishaeli ◽

M Miller ◽

AA Zayed ◽

D Huntsman ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

High Sensitivity ◽

Breast Cancer Patients ◽

High Sensitivity Detection ◽

Sensitivity Detection

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Assay of serum E2 concentration in postmenopausal breast cancer patients using a high-sensitivity RIA method is generally useful

The Journal of Medical Investigation ◽

10.2152/jmi.63.236 ◽

2016 ◽

Vol 63 (3.4) ◽

pp. 236-240 ◽

Cited By ~ 1

Author(s):

Masami Morimoto ◽

Masako Takahashi ◽

Junko Honda ◽

Takahiro Yoshida ◽

Mitsuteru Yoshida ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Postmenopausal Breast Cancer ◽

High Sensitivity ◽

Breast Cancer Patients

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Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) Spectroscopy Analysis of Saliva for Breast Cancer Diagnosis

Journal of Oncology ◽

10.1155/2020/4343590 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Izabella C. C. Ferreira ◽

Emília M. G. Aguiar ◽

Alinne T. F. Silva ◽

Letícia L. D. Santos ◽

Léia Cardoso-Sousa ◽

...

Keyword(s):

Breast Cancer ◽

Fourier Transform ◽

Ftir Spectroscopy ◽

Cancer Patients ◽

Sensitivity And Specificity ◽

Fourier Transform Infrared ◽

Total Reflection ◽

Attenuated Total Reflection ◽

Breast Cancer Patients ◽

Potential Use

Saliva biomarkers using reagent-free biophotonic technology have not been investigated as a strategy for early detection of breast cancer (BC). The attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy has been proposed as a promising tool for disease diagnosis. However, its utilization in cancer is still incipient, and currently saliva has not been used for BC screening. We have applied ATR-FTIR onto saliva from patients with breast cancer, benign breast disease, and healthy matched controls to investigate its potential use in BC diagnosis. Several salivary vibrational modes have been identified in original and second-derivative spectra. The absorbance levels at wavenumber 1041 cm−1 were significantly higher (p<0.05) in saliva of breast cancer patients compared with those of benign patients, and the ROC curve analysis of this peak showed a reasonable accuracy to discriminate breast cancer from benign and control patients. The 1433–1302.9 cm−1 band area was significantly higher (p<0.05) in saliva of breast cancer patients than in control and benign patients. This salivary ATR-FTIR spectral area was prevalidated as a potential diagnostic biomarker of BC. This spectral biomarker was able to discriminate human BC from controls with sensitivity and specificity of 90% and 80%, respectively. Besides, it was able to differentiate BC from benign disease with sensitivity and specificity of 90% and 70%, respectively. Briefly, for the first time, saliva analysis by ATR-FTIR spectroscopy has demonstrated the potential use of salivary spectral biomarkers (1041 cm−1 and 1433–1302.9 cm−1) as a novel alternative for noninvasive BC diagnosis, which could be used for screening purposes.

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N-glycolylneuraminic acid serum biomarker levels are elevated in breast cancer patients at all stages of disease.

10.1101/2021.06.21.449179 ◽

2021 ◽

Author(s):

Lucy K Shewell ◽

Christopher J. Day ◽

Jamie R Kutasovic ◽

Jodie L Abrahams ◽

Jing Wang ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Patients ◽

Early Stage ◽

Specific Binding ◽

High Sensitivity ◽

Disease Recurrence ◽

Serum Biomarker ◽

Breast Cancer Patients ◽

Sialic Acid Binding

N-glycolylneuraminic acid (Neu5Gc) is an aberrant glycosylation that has been proposed as a cancer biomarker. Using a Neu5Gc-specific lectin called SubB2M in a Surface Plasmon Resonance (SPR)-based assay, we previously reported elevated Neu5Gc biomarkers in serum from ovarian cancer patients. Here we report an optimized SubB2M SPR-based assay to enhance specificity with a non-sialic acid binding version of SubB2M, SubBA12, to control for any non-specific binding to SubB2M, which improved discrimination of cancer-free controls from early-stage ovarian cancer. Using this new assay, sera from breast cancer cases were analysed, revealing significantly elevated levels of Neu5Gc biomarkers at all stages of breast cancer. We show that Neu5Gc serum biomarker levels can discriminate breast cancer patients from cancer-free individuals with high sensitivity and specificity. Analysis of serum collected prospectively, post-diagnosis, from breast cancer patients at high risk for disease recurrence showed a trend for a decrease in Neu5Gc levels immediately following treatment for those in remission. Neu5Gc serum biomarkers are a promising new tool for early detection and disease monitoring for breast cancer that may complement current imaging- and biopsy-based approaches.

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Abstract 12538: Effect of High Intensity Interval Training on High-sensitivity C-reactive Protein in Breast Cancer Patients Undergoing Anthracycline-based Chemotherapy

Circulation ◽

10.1161/circ.142.suppl_3.12538 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Kyuwan Lee ◽

Christina Dieli-Conwright

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Interval Training ◽

High Sensitivity ◽

Breast Cancer Patients ◽

High Intensity Interval Training ◽

C Reactive Protein ◽

Reactive Protein ◽

High Intensity Interval ◽

Circulating Levels

Introduction: Anthracycline-based chemotherapies are widely used chemotherapeutic agents for treatment of breast cancers, but these agents increase inflammation in the cardiovascular system. Circulating levels of high sensitivity C-reactive protein (hsCRP) have been validated to assess the degree of inflammation in adults. While exercise has been shown to reduce hsCRP in patients with coronary artery diseases, it is unclear whether high intensity interval training (HIIT) reduces hsCRP in breast cancer patients undergoing anthracycline-based chemotherapy. Hypothesis: We hypothesized that a group of participants that performed the 8-week HIIT intervention would demonstrate maintenance in hsCRP level compared to a group of participants that did not perform HIIT. Methods: Thirty breast cancer survivors were randomized to either the HIIT or control (CON) group. The HIIT group participated in 8 weeks of supervised exercise sessions 3 times/week. The CON group was asked to maintain their current activity levels. Fasting (≥ 12 hours) blood (∽30 cc) was obtained from the antecubital and hsCRP was measured by immunoturbidimetric assay. A paired t-test and 2x2 (group x time) repeated measures ANOVA were used to evaluate changes in hsCRP. Results: At baseline, there were no group differences in age (46.9±9.8 yrs), BMI (31.0±7.5 kg/m 2 ) and blood pressure (123.4 ± 16.8/72.3.9 ± 5.6 mmHg; p>0.05). Following 8 weeks, hsCRP did not significantly change (7.1±2.7 to 8.7±3.5 mg/L) in the HIIT group (p=0.21). However, there was a significant within-group change in the CON group (6.0±3.2 to 10.9.1±2.3 mg/L; p=0.02). There was no group x time interaction following 8 weeks (P=0.93). Conclusions: An 8-week HIIT intervention maintained circulating levels of hsCRP in breast cancer patients receiving anthracycline-based chemotherapy. Future large randomized controlled trials are warranted to investigate the impact of exercise-induced reductions in inflammation while undergoing anthracycline-based chemotherapy.

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