Relevance of Flammer Syndrome Phenotype to Metastatic Breast Cancer: Risks by Pre-metastatic Systemic Hypoxic Environment

Abstract

Metastatic disease is the major cause of the death in breast cancer patient (BC) cohorts. Lymph nodes, bones, lung, liver and brain are the most frequently reported sites of the metastatic disease in BC. For example, over 20% of the entire patients’ cohort suffering from aggressive metastases in the liver are individuals with primary tumours diagnosed in the breast. Further, the brain is one of the predominant sites of the metastatic disease recorded for more than 20% of some specific BC subgroups, although in BC-free populations primary brain tumours is a rare disorder. This phenomenon has not been yet adequately explained.

The achievements of our international project have substantially extended the currently existing knowledge regarding the “Seed and Soil” theory of metastasis clearly demonstrating that a strong predisposition of individuals at risk to form the systemic hypoxic pre-metastatic niches can be established a long time before the breast malignancy is clinically manifested. The Flammer syndrome (FS) phenotype may strongly contribute to the aggressive metastatic disease. The exploitation of the acquired knowledge might be performed by creating innovative screening programmes. Contextually, we propose the FS-questionnaire to be considered by family doctors (GPs) for its practical application to the general population, in order to improve the quality of primary care by developing novel more effective approaches for the targeted prevention of the metastatic BC.