BACKGROUND: We investigated the stimulatory potential of dehydroepiandrosterone sulfate (DHEA-S) on tamoxifen-treated cells and assessed its effect on cancer progression in the adjuvant setting. METHODS: Mean serial serum levels of sex hormones from 44 patients receiving tamoxifen were correlated with follow-up status. T-47D (ER+/PR+) and HCC1937 (ER-/PR-) breast cancer cells were pretreated with 100 microM anastrozole, with or without tamoxifen, and stimulated with 22.8 microM DHEA-S. Rapid colorimetric assays allowed calculation of growth percent change. RESULTS: Clinically, development of metastatic disease correlated only with > or =90 microg/dL DHEA-S (P = 0.005). In vitro, T-47D cells stimulated with DHEA-S after anastrozole showed 35% increased growth. Addition of 0.01 nM tamoxifen demonstrated -7% inhibition. Increasing the DHEA-S/tamoxifen ratio reversed suppression to +25%. CONCLUSIONS: DHEA-S > or =90 microg/dL is a risk factor for recurrence in the adjuvant setting. In vitro, although tamoxifen inhibits cell growth at high doses it can be circumvented by DHEA-S. These results indicate that DHEA-S contributes to tamoxifen resistance and disease progression.
BACKGROUND: We investigated the stimulatory potential of dehydroepiandrosterone sulfate (DHEA-S) on tamoxifen-treated cells and assessed its effect on cancer progression in the adjuvant setting. METHODS: Mean serial serum levels of sex hormones from 44 patients receiving tamoxifen were correlated with follow-up status. T-47D (ER+/PR+) and HCC1937 (ER-/PR-) breast cancer cells were pretreated with 100 microM anastrozole, with or without tamoxifen, and stimulated with 22.8 microM DHEA-S. Rapid colorimetric assays allowed calculation of growth percent change. RESULTS: Clinically, development of metastatic disease correlated only with > or =90 microg/dL DHEA-S (P = 0.005). In vitro, T-47D cells stimulated with DHEA-S after anastrozole showed 35% increased growth. Addition of 0.01 nM tamoxifen demonstrated -7% inhibition. Increasing the DHEA-S/tamoxifen ratio reversed suppression to +25%. CONCLUSIONS:DHEA-S > or =90 microg/dL is a risk factor for recurrence in the adjuvant setting. In vitro, although tamoxifen inhibits cell growth at high doses it can be circumvented by DHEA-S. These results indicate that DHEA-S contributes to tamoxifen resistance and disease progression.
Authors: Cara L McDermott; Angela A Hsieh; Erin S Sweet; Kimberly M Tippens; Jeannine S McCune Journal: J Altern Complement Med Date: 2011-11 Impact factor: 2.579
Authors: Sharon Wayne; Marian L Neuhouser; Cornelia M Ulrich; Carol Koprowski; Charles Wiggins; Kathy B Baumgartner; Leslie Bernstein; Richard N Baumgartner; Frank Gilliland; Anne McTiernan; Rachel Ballard-Barbash Journal: Cancer Epidemiol Biomarkers Prev Date: 2008-10-28 Impact factor: 4.254