Breast cancer (BC) epidemic is recognised now worldwide as the reality of the early twenty-first century. Increasing trends in the postmenopausal BC prevalence, even for the European countries earlier demonstrating relatively stable incidence rates of the disease, are highly alarming for the healthcare givers. This new actuality requires a substantial revision of the paradigm currently applied to the BC management and creation of highly innovative concepts. Current multi-centred study highlights new complex mechanisms of the development and progression of the postmenopausal BC. Innovative concepts are presented which argue for more effective predictive and preventive approaches well justified in view of the clusters of the symptoms analysed here and demonstrated as highly prevalent in the postmenopausal breast cancer versus BC-free individuals. Another conceptual novelty presented here is a new interpretation of the "Seed and Soil" theory of metastasis in BC. According to the new concept, the "pre-metastatic niches" ("Soil") are created by a systemic hypoxia a long time before the breast malignancy is clinically manifested.

Department of Histology and Embryology and Biomedical Centre Faculty of Medicine in Plzen Charles University Prague Czech Republic Department of Neurology Faculty Hospital Plzen Plzen Czech Republic

Department of Obstetrics and Gynaecology Jessenius Faculty of Medicine Martin University Hospital Martin Slovak Republic Division of Oncology Biomedical Centre Martin Jessenius Faculty of Medicine Comenius University in Bratislava Bratislava Slovak Republic

Department of Ophthalmology University of Basel Basel Switzerland

European Medical Association EMA Brussels Belgium

Faculty of Medical Sciences University Goce Delcev Stip Stip Macedonia Diabetes and Metabolic Disorders University Clinic of Endocrinology Skopje Macedonia

Radiological clinic Rheinische Friedrich Wilhelms University of Bonn Sigmund Freud Str 25 53105 Bonn Germany Breast Cancer Research Centre Rheinische Friedrich Wilhelms University of Bonn Bonn Germany Centre for Integrated Oncology Cologne Bonn Rheinische Friedrich Wilhelms University of Bonn Bonn Germany

University Clinic of Radiotherapy and Oncology Skopje Macedonia

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