Stress in Metastatic Breast Cancer: To the Bone and Beyond

Simple Summary Breast cancer is the most common cancer affecting women of all ages worldwide. In spite of the encouraging advances made in early diagnosis, 10% of breast cancer patients are still affected with metastatic breast cancer at the time of diagnosis. The available therapeutic options are predominantly palliative, and thus this unfavourable prognosis is associated with a low survival rate. Intriguingly, stress has been shown to promote the growth of breast tumours and the incidence of metastasis. Herein, we describe the contribution of the sympathetic hyperactivation induced by stress to the progression of breast cancer and its dissemination to distant organs, specifically to the bone, but also to the lung, liver and brain. The putative sympathetic adrenergic signalling mechanisms responsible for this modulation are also summarised. The knowledge gathered highlights the therapeutic potential of targeting sympathetic signalling to tackle cancer progression and metastasis. Breast cancer (BRCA) remains as one the most prevalent cancers diagnosed in industrialised countries. Although the overall survival rate is high, the dissemination of BRCA cells to distant organs correlates with a significantly poor prognosis. This is due to the fact that there are no efficient therapeutic strategies designed to overcome the progression of the metastasis. Over the past decade, critical associations between stress and the prevalence of BRCA metastases were uncovered. Chronic stress and the concomitant sympathetic hyperactivation have been shown to accelerate the progression of the disease and the metastases incidence, specifically to the bone. In this review, we provide a summary of the sympathetic profile on BRCA. Additionally, the current knowledge regarding the sympathetic hyperactivity, and the underlying adrenergic signalling pathways, involved on the development of BRCA metastasis to distant organs (i.e., bone, lung, liver and brain) will be revealed. Since bone is a preferential target site for BRCA metastases, greater emphasis will be given to the contribution of alpha 2- and beta-adrenergic signalling in BRCA bone tropism and the occurrence of osteolytic lesions.