Development of cross-resistance to tamoxifen in raloxifene-treated breast carcinoma cells

Anticancer Res. May-Jun 2002;22(3):1379-83.


Selective estrogen receptor modifiers (SERMs) are used chronically in the treatment of breast cancer and osteoporosis but some patients become resistant, at which point second-line SERMs are considered as options. Because the use of SERMs is increasing and breast cancer is so common, we tested the hypothesis that treatment with SERMs can induce cross-resistance to other SERMs. We used three cultured breast carcinoma cell lines (MCF-7, ZR-75-1, and T47D) which are estrogen-receptor-positive (ER+) and are prone to developing resistance to hormonal treatment. Cell lines were exposed to increasing doses of raloxifene. Raloxifene-resistant clones were selected and tested for cross-resistance to tamoxifen. Compared to untreated cells, raloxifene-resistant clones showed an increased IC50 (reduced potency) of about 15,000-fold with no apparent change in maximal inhibition of cell growth. These same raloxifene-resistant clones were also about 15-fold more resistant to the growth-inhibiting effects of tamoxifen. While the resistance to tamoxifen is considerably less marked (1000-fold less), it is large enough to raise the question as to whether patients who become resistant to raloxifene will benefit by switching to tamoxifen or vice versa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm
  • Humans
  • Inhibitory Concentration 50
  • Raloxifene Hydrochloride / pharmacology*
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Tamoxifen / pharmacology*
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Hormonal
  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • Raloxifene Hydrochloride