Abstract
Breast cancer is a multifactorial disease classified by several sub-types which differ from each other by risk factors, specific molecular promoters and severity of outcomes. Tumour aggressiveness and metastatic disease are the key determinants of breast cancer outcomes. Tumour cell ability to degrade the extracellular matrix and to be motile is the hallmark of invasion and essential step in a development of breast cancer metastatic disease. Therefore, a coordinated action between cell motility and ability to degrade the extracellular matrix is currently under extensive investigation focused on molecular targets for both diagnostic and therapeutic purposes. Contextually, our current study was dedicated to patient stratification utilising MMP-9 serum activity levels and RhoA expression patterns measured in circulating leucocytes. Biomarker patterns were “masked” in non-stratified patient groups. In contrast, the multiparametric stratification approach led to highly improved clinical utility of biomarker patterns. Presented stratification system is recommended for population screening as a cost-effective non-invasive approach to facilitate predictive diagnostics of breast cancer predisposition, pre-lesions and early stages, when the pathology can be effectively prevented or cured. Proposed approach might be particularly useful for early and predictive breast cancer diagnostics applied to certain phenotypes such as premenopausal rather than postmenopausal women, women with dense breast tissue, where highly increased RhoA/MMPs activities are utilised for effective proteolysis of the matrix and cancer cell migration into dense matrices, as well as for breast cancer of unclear origin such as particularly aggressive triple-negative sub-type.
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Acknowledgements
The authors thank the European Association for Predictive, Preventive and Personalised Medicine (EPMA, Belgium) for professional and financial support of the project. Further, our cordial thanks belong to Prof. Dr. J. Flammer, University of Basel, Switzerland for professional considerations of potential implementing areas for the stratification system published here and critical reading of the manuscript. For the performance of “Western-blot” analysis, the authors thank Mrs. G. Windisch-Schuster, Department of Radiology, University of Bonn.
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The study funding has been performed by the Breast Cancer Research Centre, University of Bonn, Bonn, Germany. KY has been awarded with corresponding fellowship by the European Association for Predictive, Preventive and Personalised Medicine (EPMA, Belgium).
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The authors declare that they have no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Golubnitschaja, O., Yeghiazaryan, K., Abraham, JA. et al. Breast cancer risk assessment: a non-invasive multiparametric approach to stratify patients by MMP-9 serum activity and RhoA expression patterns in circulating leucocytes. Amino Acids 49, 273–281 (2017). https://doi.org/10.1007/s00726-016-2357-2
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DOI: https://doi.org/10.1007/s00726-016-2357-2