BACKGROUND: Tamoxifen is considered an antiestrogen against breast cancer, yet it has known estrogenic side effects. We hypothesized that long- term administration of tamoxifen may significantly increase circulating estrogen levels in women with breast cancer. METHODS: Serum dehydroepiandrosterone (DHEA), estrone (E1), and estradiol (E2) levels were prospectively measured in 47 breast cancer patients before and during tamoxifen therapy for 2 years. Differences in baseline and peak hormone levels during treatment were compared, and significance was determined by paired Student's t test. RESULTS: Mean DHEA levels increased by 133% from 61 mg/L to 142 mg/L (P <0.001) and mean E2 levels increased by 239% from 28 pg/mL to 95 pg/mL (P <0.05). Mean E1 levels increased by 264% from 42 pg/mL to 153 pg/mL (P = 0.06). CONCLUSIONS: Long-term tamoxifen therapy can be associated with increased serum levels of DHEA, E1, and E2. Elevated serum estrogens may explain tamoxifen's estrogenic effects and may represent a mechanism for the development of drug resistance.
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