The Significance of Serum HER2 Levels at Diagnosis on Intrinsic Subtype-Specific Outcome of Operable Breast Cancer Patients

Lee, Moo Hyun; Jung, So‐Youn; Kang, Sanggil; Song, Eun Jin; Park, In Hae; Kong, Sun‐Young; Kwon, Younggoo; Lee, Keun Seok; Kang, Hyejin

doi:10.1371/journal.pone.0163370

Cited by 19 publications

(18 citation statements)

References 23 publications

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“…Furthermore, a significant association was found between cats with HER2-overexpressing mammary carcinomas (luminal B-like and HER2+ subtypes) and cats with high serum SDF-1 levels, as reported for breast cancer patients [ 40 , 43 ]. Indeed, cats with elevated serum SDF-1 levels have 53 times more likelihood to show HER2-positive tumor status and increased serum HER2 values ( p <0.0001), corroborating the recent data that associates the HER2 tumor status with the serum HER2 levels [ 11 ], as also reported in humans [ 55 , 56 ]. Further ROC analysis also revealed a cut-off value of 4 ng/ml in serum levels, that allows differentiation of HER-2 positive from HER-2 negative tumor samples.…”

Section: Discussionsupporting

confidence: 86%

Serum SDF-1 levels are a reliable diagnostic marker of feline mammary carcinoma, discriminating HER2-overexpressing tumors from other subtypes

et al. 2017

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The feline mammary carcinoma (FMC) is the third most common tumor in cat, sharing many clinicopathological features with human breast cancer and thus, considered a suitable model for comparative oncology. Due to its poor prognosis, further studies are required to improve the diagnostic accuracy and treatment of cats with spontaneous mammary carcinoma. Recently, it was reported that the overexpression of stromal cell-derived factor-1 (SDF-1) has great value in human breast cancer diagnosis, suggesting that diagnostic tools and therapies targeting the SDF-1 ligand can improve the clinical outcome. In this study, we aimed to evaluate if serum SDF-1 levels can also be used as a biomarker of mammary carcinoma in cats and to analyze if serum SDF-1 levels are associated with clinicopathological features, linked to a specific FMC subtype or correlated with the tumor expression of SDF-1 receptor, the chemokine C-X-C motif receptor 4 (CXCR4). Results showed that cats with mammary carcinoma had significantly higher serum SDF-1 levels than healthy controls (p=0.035) and ROC analysis revealed that the best cut-off value to differentiate sick from healthy animals was 2 ng/ml (specificity: 80%; sensitivity: 57%; AUC=0.715). Significant associations were also found between cats with elevated serum SDF-1 concentrations (≥ 2 ng/ml) and HER2-overexpressing mammary carcinomas (Luminal B-like and HER2-positive subtypes, p<0.0001), CXCR4-negative mammary carcinomas (p=0.027), mammary carcinomas with small size (<3 cm, p=0.027) and tumors with low Ki-67 expression (p=0.012). No statistical associations were found between serum SDF-1 levels and overall or disease-free survival. In summary, our results show that serum SDF-1 levels can be used as a biomarker of feline mammary carcinoma, especially in cats with HER2-overexpressing mammary tumors. Data suggest that targeted therapies against the SDF-1 ligand and/or its CXC4 receptor may be effective for the treatment of FMC, as described for human breast cancer, strengthening the concept that spontaneous feline mammary carcinoma is a suitable model for comparative oncology.

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Section: Discussionsupporting

confidence: 86%

Serum SDF-1 levels are a reliable diagnostic marker of feline mammary carcinoma, discriminating HER2-overexpressing tumors from other subtypes

et al. 2017

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“…Surgery or biopsy tumor samples were collected from patients with stage 1–4 breast cancer treated at the National Cancer Center, Korea, between July 2014 and September 2017. Tumor samples were tested for estrogen receptor (ER) status (+/−), progesterone receptor (PR) status (+/−), and HER2 (human epidermal growth factor receptor 2, also known as ERBB2) status (+/−) using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) approaches [39,40]. Receptor positivity was accessed according to the 2010 and 2013 American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines [41,42].…”

Section: Methodsmentioning

confidence: 99%

Integrative In Vivo Drug Testing Using Gene Expression Signature and Patient-Derived Xenografts from Treatment-Refractory HER2 Positive and Triple-Negative Subtypes of Breast Cancer

Ryu

Sim

Park

et al. 2019

Cancers

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Patient-derived xenografts (PDXs) are powerful tools for translational cancer research. Here, we established PDX models from different molecular subtypes of breast cancer for in vivo drug tests and compared the histopathologic features of PDX model tumors with those of patient tumors. Predictive biomarkers were identified by gene expression analysis of PDX samples using Nanostring nCount cancer panels. Validation of predictive biomarkers for treatment response was conducted in established PDX models by in vivo drug testing. Twenty breast cancer PDX models were generated from different molecular subtypes (overall success rate, 17.5%; 3.6% for HR+/HER2−, 21.4% for HR+/HER2+, 21.9% for HR−/HER2+ and 22.5% for triple-negative breast cancer (TNBC)). The histopathologic features of original tumors were retained in the PDX models. We detected upregulated HIF1A, RAF1, AKT2 and VEGFA in TNBC cases and demonstrated the efficacy of combined treatment with sorafenib and everolimus or docetaxel and bevacizumab in each TNBC model. Additionally, we identified upregulated HIF1A in two cases of trastuzumab-exposed HR−/HER2+ PDX models and validated the efficacy of the HIF1A inhibitor, PX-478, alone or in combination with neratinib. Our results demonstrate that PDX models can be used as effective tools for predicting therapeutic markers and evaluating personalized treatment strategies in breast cancer patients with resistance to standard chemotherapy regimens.

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“…This approach was used to detect biomarkers for breast cancer [27] to calibrate HER2 biomarkers, surface functionalization is improved (APTES, cross-linking glutaraldehyde, immobilization of HER2 antibody, blocking by bovine serum albumin) at minimized non-specific interaction. The lowest detectable concentration is 2 μg/L, whereas the cut-off level is 15 μg/L serum [28]. An interesting approach is the combination of optical and opto-acoustic microscopy to image thin samples to make it more accessible to the biomedical community [202].…”

Section: Structured Fibers and Waveguidesmentioning

confidence: 99%

Critical assessment of relevant methods in the field of biosensors with direct optical detection based on fibers and waveguides using plasmonic, resonance, and interference effects

Gauglitz

2020

Anal Bioanal Chem

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Direct optical detection has proven to be a highly interesting tool in biomolecular interaction analysis to be used in drug discovery, ligand/receptor interactions, environmental analysis, clinical diagnostics, screening of large data volumes in immunology, cancer therapy, or personalized medicine. In this review, the fundamental optical principles and applications are reviewed. Devices are based on concepts such as refractometry, evanescent field, waveguides modes, reflectometry, resonance and/or interference. They are realized in ring resonators; prism couplers; surface plasmon resonance; resonant mirror; Bragg grating; grating couplers; photonic crystals, Mach-Zehnder, Young, Hartman interferometers; backscattering; ellipsometry; or reflectance interferometry. The physical theories of various optical principles have already been reviewed in detail elsewhere and are therefore only cited. This review provides an overall survey on the application of these methods in direct optical biosensing. The "historical" development of the main principles is given to understand the various, and sometimes only slightly modified variations published as "new" methods or the use of a new acronym and commercialization by different companies. Improvement of optics is only one way to increase the quality of biosensors. Additional essential aspects are the surface modification of transducers, immobilization strategies, selection of recognition elements, the influence of non-specific interaction, selectivity, and sensitivity. Furthermore, papers use for reporting minimal amounts of detectable analyte terms such as value of mass, moles, grams, or mol/L which are difficult to compare. Both these essential aspects (i.e., biochemistry and the presentation of LOD values) can be discussed only in brief (but references are provided) in order to prevent the paper from becoming too long. The review will concentrate on a comparison of the optical methods, their application, and the resulting bioanalytical quality.

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The Significance of Serum HER2 Levels at Diagnosis on Intrinsic Subtype-Specific Outcome of Operable Breast Cancer Patients

Cited by 19 publications

References 23 publications

Serum SDF-1 levels are a reliable diagnostic marker of feline mammary carcinoma, discriminating HER2-overexpressing tumors from other subtypes

Serum SDF-1 levels are a reliable diagnostic marker of feline mammary carcinoma, discriminating HER2-overexpressing tumors from other subtypes

Integrative In Vivo Drug Testing Using Gene Expression Signature and Patient-Derived Xenografts from Treatment-Refractory HER2 Positive and Triple-Negative Subtypes of Breast Cancer

Critical assessment of relevant methods in the field of biosensors with direct optical detection based on fibers and waveguides using plasmonic, resonance, and interference effects

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