Breast cancer anti-hormonal therapy and rheumatic diseases: linking the clinical to molecular world

Abstract

Anti-hormonal therapies are used in the treatment of hormone dependent breast cancer. Their use may be complicated with the onset of arthralgia and autoimmune diseases. Recently a clinical relationship between oestrogen, anti-oestrogen therapy and rheumatic diseases has been reported in the literature, but, until now, experimental supporting data about the interacting biochemical pathways involved are still very limited. The understanding of this molecular link may provide important information to elucidate the relationship between autoimmunity and cancer mechanism and treatment. This review is intended to highlight the relationship between known common molecular mechanisms which explain this association and that probably need to be investigated in future studies.

Aromatase Inhibitors—Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects

“…As suggested also by Melillo et al [169], in a recent review on the possible molecular mechanisms responsible for the onset of autoimmunity during AIs therapy, other biological pathways may involve IL-17. In a genome-wide association study, a SNP signal on chromosome 14 that mapped near the 3' end of the T-cell leukemia 1A (TCL1A) gene, was identified as being associated with musculoskeletal pain in women in adjuvant AIs therapy for BC.…”

“…In this context, IL-17 acts as a key amplifier of the inflammatory response, as it initiates the synthesis of several other inflammatory mediators, such as granulocyte-macrophage colony stimulating factor, Prostaglandin (PG)-E2 and IL-8, which, in turn, increase the inflammatory cascade [171]. The estradiol-dependent regulation of this cytokine and of its receptor expression, mediated by TCL1A, might help to explain the association of TCL1A with musculoskeletal symptoms, within the range of SpA described in patients treated with AIs [127,169]. Other pro-inflammatory cytokines, such as TNF-α and IL-1β, are known for their central role in the pathogenesis of autoimmune diseases, and previous evidence showed that estrogens modulated their release, controlling the expression of CD16 receptor on monocytes and macrophages [172].…”