Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management.

Konstantinos Venetis,Nicola Fusco,Stefania Morganti,Carmen Criscitiello,Elham Sajjadi,Marco Invernizzi,Roberto Piciotti

doi:10.3390/cells10061377

Abstract

Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on patient’s survival and overall frailty. The interplay between tumor cells and the bone microenvironment induces bone destruction and tumor progression. To date, the clinical management of bone metastatic breast cancer encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing bone resorption to reduce the risk of skeletal-related events. However, their effect on patients’ survival remains controversial. Unraveling the biology that governs the interplay between breast neoplastic cells and bone tissue would provide means for the development of new therapeutic agents. This article outlines the state-of-the art in the characterization and targeting the bone metastasis in breast cancer, focusing on the major clinical and translational studies on this clinically relevant topic.

Highlights

Breast cancer is the most prevalent malignancy and the foremost cause of cancerrelated death in women worldwide [1]
We provide an overview of the biological models and the molecular heterogeneity that characterizes bone metastasis in breast cancer
endothelin 1 (ET1) downregulates the expression of dickkopf 1 (DKK1), which allows the activation of Wnt inducing an osteoblastic phenotype in breast cancer bone metastases [57]

Summary

Introduction

Breast cancer is the most prevalent malignancy and the foremost cause of cancerrelated death in women worldwide [1]. Several therapeutic strategies to target this condition (e.g., bone-modifying agents) are currently available [9,11,12,13]. Their reliability and impact on patients’ frailty remain a subject of debate [14]. Emphasis is placed on the currently available systemic therapies and bone-modifying agents through a broad overview of the main trials involving patients with breast cancer and bone metastasis, in order to highlight the current and future therapeutic implications

Biological Mechanisms of Bone Metastasis

Bone-Targeting Therapies for Breast Cancer Patients with Bone Metastasis

Findings

Concluding Remarks