Effect of a High Bone Turnover State Induced by Estrogen Deficiency on the Development and Progression of Breast Cancer Bone Metastases
Abstract
Aromatase inhibitors (AIs), effective treatment for breast cancer, block estrogen synthesis. Increased bone resorption and decreased bone mineral density (BMD) are predicted consequences. Previous data showed variable BMD response to AI therapy in the female BALBc/ICR swiss athymic mouse. Therefore, to further define the BMD response to AI therapy in a mouse model, four-week-old female BALBc/ICR Swiss immunocompetent mice were treated with ovariectomy (OVX), sham surgery, the AI letrozole (5 mg/kg/day) or control. Ten weeks after surgery or initiation of AI/control, there was increased body weight (p<0.0001) and fat mass (p<0.0001) in OVX and letrozole-treated mice as compared to their respective controls. OVX mice had decreased BMD at the total body (p=0.0089), spine (p<0.0001), femur (p=0.0573) and tibia (p=0.0045) compared to sham mice. Letrozole-treated mice did not differ from control mice at the total body or tibia, but had decreased BMD at the spine (p=0.0018) and increased BMD at the femur (p=0.0003) compared to control. There was a significant decline in uterine weight after OVX compared to sham surgery (p<0.0001), but there was no difference in uterine weight between the letrozole and control mice. Therefore, the anticipated decline in estrogen levels with AI therapy was not seen in the BALBc/ICR Swiss immunocompetent mouse strain.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2009
- Accession Number
- ADA514579
Entities
People
- Wende M. Kozlow
Organizations
- University of Virginia