Abstract

The presence of microcalcifications in the breast microenvironment, combined with the growing evidences of the possible presence of osteoblast-like or osteoclast-like cells in the breast, suggest the existence of active processes of calcification in the breast tissue during a woman’s life. Furthermore, much evidence that osteoimmunological disorders, such as osteoarthritis, rheumatoid arthritis, or periodontitis influence the risk of developing breast cancer in women exists and vice versa. Antiresorptive drugs benefits on breast cancer incidence and progression have been reported in the past decades. More recently, biological agents targeting pro-inflammatory cytokines used against rheumatoid arthritis also demonstrated benefits against breast cancer cell lines proliferation, viability, and migratory abilities, both in vitro and in vivo in xenografted mice. Hence, it is tempting to hypothesize that breast carcinogenesis should be considered as a potential osteoimmunological disorder. In this review, we compare microenvironments and molecular characteristics in the most frequent osteoimmunological disorders with major events occurring in a woman’s breast during her lifetime. We also highlight what the use of bone anabolic drugs, antiresorptive, and biological agents targeting pro-inflammatory cytokines against breast cancer can teach us.

Highlights

  • The term “osteoimmunology” was first used in 2000 by Choi et al to define a new paradigm describing the crosstalk between the immune system and osteoclastogenesis [1]

  • Lee et al observed that the addition of Secreted Frizzled-Related Protein 1 (SFRP1), another Wnt signaling antagonist in naïve T-cells medium is responsible for T helper 17 cells (Th17) polarized T-cells differentiation

  • Numerous similarities between the microenvironment of bone tissue and the breast microenvironment in presence of hydroxyapatite microcalcifications have been highlighted in the present review (Table 1)

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Summary

Introduction

The term “osteoimmunology” was first used in 2000 by Choi et al to define a new paradigm describing the crosstalk between the immune system and osteoclastogenesis [1]. Adaptative and innate immunity could be induced by several pathological (bacteria, tissue injury) or physiological (tissue remodeling) processes Despite this variety of stimuli, the associated response remains similar between diseases: a crosstalk between myeloid lineage, mesenchymal stem cells and the inflammatory microenvironment, which results mainly in both excessive bone and cartilage resorption, and chronic inflammation, and in bone formation in some cases (Figure 1) [1,2,3,4,5,6]. Much evidence that osteoimmunological disorders such as osteoarthritis [29], rheumatoid arthritis [30,31,32,33,34] or periodontitis [35,36,37] influence the risk of developing breast cancer in women exists and vice versa. We highlight what the use of bone anabolic drugs, antiresorptive and biological agents targeting on pro-inflammatory cytokines against breast cancer can teach us

Overview of the Most Frequent Osteoimmunological Disorders
Osteoarthritis
Rheumatoid Arthritis
Periodontitis
Other Osteoimmunological Disorders
Pregnancy and Lactation
Postlactation Lobular Involution
Age-Related Lobular Involution
Inflammation in Breast Carcinogenesis
Osteoclast-Like Giant Breast Cells
Osteolytic Lesions
Osteoblastic and Mixed Lesions
Hormone Replacement Therapies
Bisphosphonates
Denosumab
Parathyroid Hormone Analog
Parathyroid Hormone Related Protein Analog
Findings
Conclusions
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