The effect of high dehydroepiandrosterone sulfate levels on tamoxifen blockade and breast cancer progression

Am J Surg. 2003 May;185(5):411-5. doi: 10.1016/s0002-9610(03)00054-0.


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.

MeSH terms

  • Adult
  • Age Factors
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • Dehydroepiandrosterone Sulfate / blood*
  • Dehydroepiandrosterone Sulfate / pharmacology*
  • Disease Progression
  • Drug Resistance
  • Estrogen Antagonists / therapeutic use*
  • Female
  • Gonadal Steroid Hormones / blood
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Receptors, Estrogen / analysis
  • Retrospective Studies
  • Risk Factors
  • Tamoxifen / therapeutic use*
  • Tumor Cells, Cultured / drug effects


  • Antineoplastic Agents, Hormonal
  • Estrogen Antagonists
  • Gonadal Steroid Hormones
  • Receptors, Estrogen
  • Tamoxifen
  • Dehydroepiandrosterone Sulfate