Brain-Sparing Strategy for Breast Cancer Treatment and Prevention
Abstract
Tamoxifen is a mainstay of hormonal therapy for breast cancer patients, but its antagonism of estrogen actions in the brain has the potential of depriving women of the beneficial effects of estrogen on affect and cognition. Tamoxifen methyl iodide (TMI) was designed to obviate this potential problem through limited access to the brain confirmed by the permanent charge on the molecule. To prove that TMI and its metabolites do not penetrate the brain and/or interact with brain estrogen receptors, we have employed radioactive TMI and shown that brain levels were low to undetectable, as compared to high uptake and accumulation with tamoxifen. Furthermore, following 3 weeks of continuous exposure, there was no evidence for occupancy of brain ER in the TMI treated animals as compared to highly significant occupancy with tamoxifen and estradiol. These results , combined with the efficacy of the compound in animal models of human breast cancer, support further development and evaluation of TMI in human subjects.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA407295
Entities
People
- Anat Biegon
Organizations
- University of California, Berkeley