Combining serum autoantibody measurements with traditional serum biomarkers for the detection of invasive breast cancer.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 13-13
Author(s):  
Meredith C. Henderson ◽  
David Emery Reese ◽  
Sherri Borman ◽  
Susan Yeh ◽  
Alan Hollingsworth
Keyword(s):  
Breast Cancer ◽  
Serum Protein ◽  
Invasive Breast Cancer ◽  
Serum Proteins ◽  
Wide Spectrum ◽  
Great Promise ◽  
Breast Cancer Patients ◽  
Intrinsic Variability ◽  
Protein Biomarkers ◽  
Meso Scale Discovery

13 Background: The use of protein biomarkers for serum-based detection of invasive breast cancer has been problematic due in large part to intrinsic variability in the population as a whole. The Provista Biomarker Assay (PBA) has been shown previously to be highly sensitive across a wide spectrum of clinical signals. The detection of autoantibodies (AAb) holds great promise due to the inherent specificity these biomarkers provide. However, as a clinical-quality diagnostic, it is necessary to utilize a panel comprised of multiple autoantibodies, as individual sensitivity is general low. Our hypothesis was that combining serum protein and autoantibodies together in a panel would result in an increased ability to correctly identify breast cancer. Methods: To maximize clinical performance (sensitivity and specificity), we utilized the Meso Scale Discovery ELISA-based system to measure AAbs from patient sera. We analyzed 134 prospectively collected patient serum samples for a variety of autoantibody targets. These data, together with serum protein biomarker concentrations, produced an analytically robust test that is also highly specific. Results: Consistent with our hypothesis, the inclusion of autoantibodies with serum proteins in the Provista Biomarker Assay improved test specificity above that observed in serum protein biomarkers alone. Individual protein targets had limited ability to differentiate benign conditions from invasive breast cancer. However, factoring in autoantibody values resulted in improved overall accuracy to differentiate serum from benign and invasive breast cancer patients. Conclusions: In the novel approach of combining these two different classes of analytes, we exploit the specificity of AAbs while maintaining high sensitivity through the inclusion of more generalized cancer-associated protein biomarkers. The combination of these two approaches clearly offers unique performance benefits in the early detection of invasive breast cancer that is greater than either component alone.

Provista 002 prospective randomized trial utilizing Videssa in conjunction with imaging to detect breast cancer from patients with imaging findings age 25-75.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 31-31
Author(s):  
David Emery Reese ◽  
Rao Mulpuri ◽  
Kasey Benson ◽  
Elias Letsios ◽  
Christa Corn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Detection ◽  
Serum Protein ◽  
Invasive Breast Cancer ◽  
Breast Biopsy ◽  
Dense Breast ◽  
Protein Biomarkers ◽  
Serum Samples ◽  
Blood Draw ◽  
Specific Patient

31 Background: An approach to detection that relies on biochemical markers of breast cancer would significantly contribute to more accurate detection in women with suspicious lesions. The combination of imaging, which identifies anatomical anomalies consistent with cancer with proteomic approaches promises to provide a powerful detection paradigm. A proteomic detection approach would provide a powerful tool for the detection of breast cancer in women with dense breast, a diagnosis that is difficult utilizing imaging alone. While protein signatures for the presence of breast cancer have remained elusive, we have developed a novel approach that combines serum protein biomarkers with tumor-associated autoantibodies. We utilized prospectively collected serum samples to develop novel algorithms for use in conjunction with imaging. We tested whether the assay was able to distinguish benign from invasive breast cancers in a prospective, randomized setting. Methods: Provista-002 enrolled 509 patients from multiple sites across the US and followed for 6 months after the first blood draw under IRB approval. Patients were consented after assessment of a BIRADS 3 or 4 and considered eligible if they were between 25 and 75 years of age, no history of cancer, no prior breast biopsy within the last six months, and were assessed as BIRADS 3 or 4 within 28 days. Upon enrollment, patients were randomized to either training or validation groups. Clinical truth was considered equal to or greater than 80% sensitivity and/or specificity. Serum protein biomarkers and tumor-associated autoantibodies identified in prior proteomic screens were measured prior to biopsy in a blinded and randomized fashion. Individual biomarker concentrations, together with specific patient data were evaluated using various logistic regression models developed from prior studies. Results: Provista-002 demonstrated a clear difference between women under the age of 50 from over the age of 50 in both markers required for early detection and the algorithm (models) used to distinguish benign from invasive breast cancer/DCIS. This is the first study that demonstrates clearly that modeling of proteomic patterns differs significantly in the BIRADS 3/4 setting and in the detection of early breast cancer lesions. As demonstrated in Provista – 001, we did not observe a statistical difference between early detection in women with dense breast and those with mostly fatty breast. The ability of the Videssa assay to distinguish between invasive breast cancer/DCIS from benign breast conditions was demonstrated as 85.7% sensitivity and 82.4% specificity for women under the age of 50 (although, unfortunately all lesions were pathologically confirmed to be CIS) and in women over the age of 50, the sensitivity was 86.4% and specificity was 83%. Conclusions: As above, both age groups of women needed distinct marker sets and linear regressions to distinguish benign (non-clinically significant) lesions from those that needed further evaluation (DCIS and IBC). Clinical trial information: NCT02078570.

scholarly journals Metformin improves the outcomes in Chinese invasive breast cancer patients with type 2 diabetes mellitus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tianli Hui ◽  
Chao Shang ◽  
Liu Yang ◽  
Meiqi Wang ◽  
Ruoyang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cancer Patients ◽  
Invasive Breast Cancer ◽  
Breast Cancer Patients ◽  
Diabetes Group ◽  
Metformin Group

AbstractEarly reports indicate that metformin, a clinical drug administered to treat type 2 diabetes mellitus (T2DM), was found to be associated with a better prognosis of cancer. The objective of this study was retrospectively analyzed the effect of metformin on the outcomes of Chinese breast cancer patients with T2DM. A total of 3757 primary invasive breast cancer patients who underwent surgery from January 2010 to December 2013 were enrolled. According to the medication treatment, all the patients were divided as non-diabetes group, metformin group and insulin group. The follow-up data for disease-free survival (DFS) and overall survival (OS) were obtained from 3553 patients (median follow up of 85 months) and estimated with the Kaplan–Meier method followed by a log-rank test. Multivariate Cox proportional hazards regression model was applied. The results showed that there was a significant survival difference among non-diabetes group, metformin group and insulin group, 5-year DFS was 85.8%, 96.1%, 73.0%, and 5-year OS was 87.3%, 97.1%, 73.3% respectively (P < 0.05). Prognostic analysis showed metformin was significantly associated with better DFS and OS. Our results suggested that metformin may have a good effect on the survival of invasive breast cancer patients with T2DM.

scholarly journals Stromal Cell-Derived Factor 1α (SDF-1α) in Invasive Breast Cancer: Associations with Vasculo-Angiogenic Factors and Prognostic Significance

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1952
Author(s):  
Elżbieta Zarychta ◽  
Barbara Ruszkowska-Ciastek ◽  
Kornel Bielawski ◽  
Piotr Rhone
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Stromal Cell ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Roc Curve Analysis ◽  
Stromal Cell Derived Factor ◽  
A Prospective Study

(1) Background: Tumour angiogenesis is critical for the progression of neoplasms. A prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters for estimating the probability of disease relapse in 84 primary, operable invasive breast cancer (IBrC) patients (40 (48%) with stage IA and 44 (52%) with stage IIA and IIB). (2) Methods: We explored the prognostic value of the plasma levels of SDF-1α, vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs) in breast cancer patients. The median follow-up duration was 58 months, with complete follow-up for the first event. (3) Results: According to ROC curve analysis, the optimal cut-off point for SDF-1α (for discriminating between patients at high and low risk of relapse) was 42 pg/mL, providing 57% sensitivity and 75% specificity. Kaplan–Meier curves for disease-free survival (DFS) showed that concentrations of SDF-1α lower than 42 pg/dL together with a VEGFR1 lower than 29.86 pg/mL were significantly associated with shorter DFS in IBrC patients (p = 0.0381). Patients with both SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138). (4) Conclusions: Our results imply the clinical usefulness of SDF-1α, sVEGFR1 and the number of circulating EPCs as prognostic markers for breast cancer in clinical settings.

scholarly journals Comparing the Prognostic Value of PTEN and Akt Expression with the Mitotic Activity Index in Adjuvant Chemotherapy-Treated Node-Negative Breast Cancer patients aged <55 years

2007 ◽  
Vol 29 (1) ◽  
pp. 25-35
Author(s):  
Emiel A. M. Janssen ◽  
Håvard Søiland ◽  
Ivar Skaland ◽  
Einar Gudlaugson ◽  
Kjell H. Kjellevold ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Patients ◽  
Mitotic Activity ◽  
Invasive Breast Cancer ◽  
Prognostic Value ◽  
Activity Index ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Mitotic Activity Index

Background: The prognostic value of the PI3K/Akt/mTOR pathway and PTEN in invasive breast cancer (IBC) is controversial. Cell proliferation, especially the Mitotic Activity Index (MAI), is strongly prognostic in lymph node-negative (LNneg) invasive breast cancer. However, its prognostic value has not been compared with the value of Akt and PTEN expression. Material and Methods: Prognostic comparison of Her2Neu, p110alpha (PIK3CA), Akt, mTOR, PTEN, MAI and cell-cycle regulators in 125 LNneg patients aged <55 years with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based adjuvant systemic chemotherapy. Results: Twenty-one (17%) patients developed distant metastases = DMs (median follow-up: 134 months). p110alpha correlated (p = 0.01) with pAkt but only in PTEN-negatives; pAkt correlated (p = 0.02) with mTOR. PTEN-negativity correlated with high MAI, high grade and ER-negativity (p = 0.009). The MAI was the strongest prognosticator (Hazard Ratio = HR = 2.9, p = 0.01). Her2Neu/p110α/Akt/mTOR features have no additional prognostic value to the MAI. PTEN had additional value but only in MAI < 3 (39/125 = 31%; 8% DMs). 19/39 = 49% of the MAI < 3 patients have combined MAI < 3 / PTEN+ with 0% DMs, contrasting 15% DMs in MAI < 3 / PTEN− (p = 0.03). Conclusions: In T1−3N0M0 adjuvant CMF-treated breast cancer patients aged <55 years, MAI was the strongest survival predictor. The PI3K/Akt/mTOR pathway and cell-cycle regulator characteristics had no additional prognostic value, but PTEN has. Patients with combined MAI < 3 & PTEN-positivity had 100% survival. The small subgroup of MAI < 3 patients that died were PTEN-negative.

scholarly journals Twist-mediated PAR1 induction is required for breast cancer progression and metastasis by inhibiting Hippo pathway

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Yifan Wang ◽  
Ruocen Liao ◽  
Xingyu Chen ◽  
Xuhua Ying ◽  
Guanping Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Hippo Pathway ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition

Abstract Breast cancer is considered to be the most prevalent cancer in women worldwide, and metastasis is the primary cause of death. Protease-activated receptor 1 (PAR1) is a GPCR family member involved in the invasive and metastatic processes of cancer cells. However, the functions and underlying mechanisms of PAR1 in breast cancer remain unclear. In this study, we found that PAR1 is highly expressed in high invasive breast cancer cells, and predicts poor prognosis in ER-negative and high-grade breast cancer patients. Mechanistically, Twist transcriptionally induces PAR1 expression, leading to inhibition of Hippo pathway and activation of YAP/TAZ; Inhibition of PAR1 suppresses YAP/TAZ-induced epithelial-mesenchymal transition (EMT), invasion, migration, cancer stem cell (CSC)-like properties, tumor growth and metastasis of breast cancer cells in vitro and in vivo. These findings suggest that PAR1 acts as a direct transcriptionally target of Twist, can promote EMT, tumorigenicity and metastasis by controlling the Hippo pathway; this may lead to a potential therapeutic target for treating invasive breast cancer.

scholarly journals Targeting CD82/KAI1 for Precision Therapeutics in Surmounting Metastatic Potential in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4486
Author(s):  
Maximillian Viera ◽  
George Wai Cheong Yip ◽  
Han-Ming Shen ◽  
Gyeong Hun Baeg ◽  
Boon Huat Bay
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Therapeutic Approach ◽  
Traditional Approach ◽  
Unmet Need ◽  
Great Promise ◽  
Metastasis Suppressor ◽  
Precision Oncology ◽  
Breast Cancer Patients

Metastasis is the main cause of mortality in breast cancer patients. There is an unmet need to develop therapies that can impede metastatic spread. Precision oncology has shown great promise for the treatment of cancers, as the therapeutic approach is tailored to a specific group of patients who are likely to benefit from the treatment, rather than the traditional approach of “one size fits all”. CD82, also known as KAI1, a glycoprotein belonging to the tetraspanin family and an established metastasis suppressor, could potentially be exploited to hinder metastases in breast cancer. This review explores the prospect of targeting CD82 as an innovative therapeutic approach in precision medicine for breast cancer patients, with the goal of preventing cancer progression and metastasis. Such an approach would entail the selection of a subset of breast cancer patients with low levels of CD82, and instituting an appropriate treatment scheme tailored towards restoring the levels of CD82 in this group of patients. Proposed precision treatment regimens include current modalities of treating breast cancer, in combination with either clinically approved drugs that could restore the levels of CD82, CD82 peptide mimics or non-coding RNA-based therapeutics.

Gasdermin D as a potential prognosis and treatment response prediction biomarker for invasive breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12548-e12548
Author(s):  
Xianghou Xia ◽  
Wenjuan Yin ◽  
Jiefei Mao ◽  
Jiejie Hu ◽  
Dehong Zou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Invasive Breast Cancer ◽  
Response Prediction ◽  
Chemotherapy Response ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter ◽  
Treatment Response Prediction

e12548 Background: Pyroptosis is a type of inflammatory cell death mediated by gasdermins. Pyroptosis is critical for macrophage against pathogen infection. Recently growing evidences show that pyroptosis may affect development and progression of many cancers. We aim to explore the expression and related function of pyroptosis executioner Gasdermin D (GSDMD) in breast cancer. Methods: We investigated the expression level of GSDMD using TNM plotter and Breast Cancer landscape proteome with TCGA, GTEx and TARGET databases, and the prognostic value of GSDMD in invasive breast cancer using Kaplan-Meier plotter with TCGA, GEO and EGA databases. The treatment response prediction values of GSDMD in invasive breast were calculated using ROC-plotter with GEO database. Further validation of the prognostic value and chemotherapy response prediction value of GSDMD were carried out with immunohistochemical staining on tissues from 165 cases of breast cancer patients receiving neoadjuvant chemotherapy in our cancer center. Results: TNM plotter and breast cancer landscape proteome portal analysis shows that overall expression level of GSDMD in invasive breast cancer tissue is 1.67 folds higher than it is in breast normal tissues ( p=1.05*e-06). Expression of GSDMD in LuminalB subtype (p=0.019) and Her2 subtype(p=0.04) is significantly higher than it is in TNBC subtype. Calculations with Kaplan-Meier plotter show expression of GSDMD is negatively correlated with overall survival(OS), HR=0.61(0.4−0.95) p=0.027 and relapse free survival (RFS), HR =0.65(0.58−0.63), p=8.7*e-14 and distant metastasis free survival (DMFS) HR =0.75(0.61−0.91), p=0.0038 in breast cancer patients. ROC-plotter calculations show high GSDMD expression is a powerful endocrine therapy (AUC=0.731 p=6*e-09 ) and chemotherapy response (AUC=0.64 p=8*e-05 ) predictor based on 5-year RFS in overall breast cancer patients. Our IHC staining analysis shows consistent prognostic and chemotherapy prediction value of GSDMD expression in TNBC patients. Conclusions: In conclusion, our findings suggest that high expression of GSDMD is positively correlated with prognosis and therapeutic response in breast cancer. GSDMD is a promising prognostic marker and therapeutic response predictor in invasive breast cancer.

FRI0576 IDENTIFICATION OF SERUM PROTEIN BIOMARKERS ASSOCIATED WITH RA DISEASE SEVERITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 891-892
Author(s):  
D. Galbraith ◽  
M. Caliskan ◽  
O. Jabado ◽  
S. Hu ◽  
R. Fleischmann ◽  
...  
Keyword(s):  
Disease Severity ◽  
Serum Protein ◽  
Dynamic Range ◽  
Serum Proteins ◽  
Differentially Expressed ◽  
Protein Abundance ◽  
Healthy Individuals ◽  
Protein Biomarkers ◽  
Research Support ◽  
Baseline Serum

Background:RA is a systemic autoimmune disease with heterogeneous manifestation. Recent advances in serum proteomics, such as the SomaScan®platform (SomaLogic, Inc., Boulder, USA), allow for a deeper exploration of the protein biomarkers associated with RA and a better understanding of the molecular aetiology of the disease.Objectives:To characterise the differences in baseline serum proteome of patients with RA (enrolled in the Phase IIIb Abatacept vs adaliMumab comParison in bioLogic-naïvERA subjects with background MTX [AMPLE] study)1compared with a healthy population, and to identify serum protein biomarkers associated with disease severity and radiographic progression.Methods:Patients in the AMPLE study had an inadequate response to MTX and were naïve to biologic DMARDs. Protein abundance was assessed in baseline serum samples from 440 AMPLE study patients and 123 healthy individuals with matching demographics using the SomaScan®platform, with 5000+ slow off-rate modified aptamers and up to 8 log of dynamic range.2Differential abundance testing was performed using linear models to identify differences in protein abundance in patients with RA vs healthy individuals. A separate analysis using a linear model was conducted in only the patients with RA to identify the proteins associated with DAS28 (CRP) and TSS. Pathway analyses were performed for proteins significantly (false discovery rate-adjusted p value <0.05) associated with RA and the disease severity measurements to identify over-representation of the molecular pathways.Results:Compared with healthy individuals, >2000 serum proteins were significantly differentially expressed in patients with RA, including many proteins that have been associated with RA (e.g. serum amyloid A [SAA], CRP) and complement. Most of the protein expression differences were of small magnitude (fold change <2). Proteins that were differentially expressed between patients with RA and healthy individuals were enriched in interleukin signalling, neutrophil degranulation, platelet activation/degranulation and extracellular matrix organisation pathways. DAS28 (CRP) was significantly associated with several biomarkers, including SAA, fibrinogen and CRP; in general, proteins associated with DAS28 (CRP) were most strongly enriched in the platelet activation/degranulation pathways (Figure 1), also seen in patients with RA vs healthy individuals. Additionally, many proteins were significantly associated with TSS, including SAA, matrix metalloproteinase-3 and cartilage acidic protein 1. Here, the proteins were most strongly enriched in the extracellular matrix remodelling pathways (Figure 2).Conclusion:Our study revealed that thousands of serum proteins are differentially expressed and several pathways are dysregulated between patients with RA and healthy individuals. Additional pathways were identified that reflect disease severity, including joint damage, distinct from those pathways associated with the disease. The SomaScan®platform provides a unique proteomic tool with a wide dynamic range for the identification of serum protein biomarkers associated with RA and disease severity. Proteomic signatures should be considered in clinical trials to better understand disease pathogenesis and predict risk in response to treatment.References:[1]Schiff M, et al.Ann Rheum Dis2014;73:86–94.[2]Gold L, et al.PLoS One2010;5:e15004.Acknowledgments:Rachel Rankin (medical writing, Caudex; funding: Bristol-Myers Squibb)Disclosure of Interests:David Galbraith Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Minal Caliskan Employee of: Bristol-Myers Squibb, Omar Jabado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sarah Hu Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Michael Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo, Lily, Sanofi/Regeneron, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Crescendo, Gilead, Horizon, Lily, Pfizer, Roche, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Michael A Maldonado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sheng Gao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

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