De-Escalating Breast Cancer Therapy.

The potential value of de-escalation in breast cancer therapy cannot be overstated. From reducing complications and morbidity of surgical therapy to the avoidance of chemotherapy in certain populations, the benefits of eliminating low-value therapies are significant. Further, those interventions that have minimal to no benefit may also further low-risk care cascades resulting in additional treatments or interventions without associated value, with increased financial toxicity, and resulting excess health care expenditures.

Shear Stress in Bone Marrow has a Dose Dependent Effect on cFos Gene Expression in In Situ Culture.

INTRODUCTION: Mechanical stimulation of bone is necessary to maintain its mass and architecture. Osteocytes within the mineralized matrix are sensors of mechanical deformation of the hard tissue, and communicate with cells in the marrow to regulate bone remodeling. However, marrow cells are also subjected to mechanical stress during whole bone loading, and may contribute to mechanically regulated bone physiology. Previous results from our laboratory suggest that mechanotransduction in marrow cells is sufficient to cause bone formation in the absence of osteocyte signaling. In this study, we investigated whether bone formation and altered marrow cell gene expression response to stimulation was dependent on the shear stress imparted on the marrow by our loading regime. METHODS: Porcine trabecular bone explants were cultured in an in situ bioreactor for 5 or 28 days with stimulation twice daily. Gene expression and bone formation were quantified and compared to unstimulated controls. Correlation was used to assess the dependence on shear stress imparted by the loading regime calculated using computational fluid dynamics models. RESULTS: Vibratory stimulation resulted in a higher trabecular bone formation rate (p = 0.01) and a greater increase in bone volume fraction (p = 0.02) in comparison to control explants. Marrow cell expression of cFos increased with the calculated marrow shear stress in a dose-dependent manner (p = 0.002). CONCLUSIONS: The results suggest that the shear stress due to interactions between marrow cells induces a mechanobiological response. Identification of marrow cell mechanotransduction pathways is essential to understand healthy and pathological bone adaptation and remodeling.