Molecular Mechanism for Breast Cancer Incidence in the Women's Health Initiative
Abstract
The Women's Health Initiative (WHI) was designed to evaluate the benefits of hormone replacement therapy. The primary goal was to establish the value of synthetic progestin and estrogen or estrogen alone to reduce the risk of coronary heart disease (CHD). The estrogen/synthetic progestin trial was stopped at 5.2 years and the estrogen trial was stopped after 6.8 years. Although the estrogen/synthetic progestin trial was stopped for the anticipated rise in the risk of breast cancer, the estrogen trial was stopped for elevation of strokes. Women taking estrogen/synthetic progestin or estrogen alone had no benefit from a reduction in CHD. Paradoxically, there was a decrease in breast cancer incidence in the estrogen trial. The decrease in breast cancer was sustained. The elevation of breast cancer in the estrogen/synthetic progestin trial was also sustained a decade after stopping treatment. Evidence is presented to explain the paradoxical sustained decrease in breast cancer with estrogen and the mechanism for the reversal of breast cancer incidence and mortality with the mixed synthetic progestin/glucocorticoid actions of the synthetic progestin used with estrogen in women with an intact uterus. The fact that the WHI study had an estrogen deprivation gap of at least 5 years, introduced an experimental biological dimension not observed in medical practice using progestin/estrogen hormone replacement. The evidence presented confirms the known human cancer biology of estrogen action.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 01, 2020
- Source ID
- 10.1158/1940-6207.capr-20-0082
Entities
People
- V. Craig Jordan
Organizations
- Avon Foundation for Women
- Canada Excellence Research Chairs
- National Institutes of Health
- Robert H. Lurie Comprehensive Cancer Center
- Susan G. Komen for the Cure
- United States Department of Defense
- University of Texas at Austin