In earlier studies, the evolution of breast cancer cell resistance in vivo was described; short-term antiestrogen therapy (1 to 2 years) caused the ER-positive breast cancer cells to grow robustly with tamoxifen (Gottardis and Jordan, 1988; Gottardis et al., 1989); however, 5 years of estrogen deprivation with tamoxifen created a cell phenotype in which cells have enhanced growth rate, but treatment of transplanted animals with low-dose E2 induced apoptosis (Yao et al., 2000). The gene discussed is ESR1; the disease is breast cancer.