title: Selective estrogen receptor modulators as inhibitors of repopulation of human breast cancer cell lines after chemotherapy.
abstract: OBJECTIVE
  Repopulation of surviving tumor cells between courses of chemotherapy might lead to effective drug resistance. Here we study inhibition of repopulation of hormone-responsive human breast cancer cell lines by selective estrogen receptor (ER) modulators (SERMs) during courses of chemotherapy.
  
  
  METHODS
  Hormone responsive breast cancer cell lines MCF-7 and T47D, and the ER- cell line MDA-231, were treated with either 4-hydroxy tamoxifen (4OHT) or arzoxifene during weekly courses of treatment with 5-fluorouracil (5-FU) or methotrexate (MTX). Clonogenic assays were performed to determine the overall survival of tumor cells after treatment with the SERMs alone, after one to three doses of 5-FU or MTX alone, and after 5-FU or MTX followed by each of the SERMs.
  
  
  RESULTS
  Both SERMs inhibited the growth of ER+ cells MCF-7 and T47D but had no effect on the ER-cell line MDA-231. Arzoxifene was more effective than 4OHT. Between courses of treatment with either 5-FU or MTX, repopulation of ER+ cells was specifically inhibited by the SERMs, whereas repopulation of ER- MDA-231 was not affected.
  
  
  CONCLUSIONS
  Arzoxifene and 4OHT can inhibit specifically the repopulation of ER+ breast cancer cells between courses of chemotherapy. Scheduling of short-acting SERMs between courses of chemotherapy has the potential to improve therapeutic index.
authors.affiliation: Division of Experimental Therapeutics and Department of Medical Oncology and Hematology, Princess Margaret Hospital and University of Toronto, Toronto, Ontario M5G 2M9 Canada.
authors.forename: Wu
authors.initials: W
authors.lastname: Licun
authors.forename: Ian F
authors.initials: IF
authors.lastname: Tannock
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D010880:Piperidines / Q000008:administration & dosage; D011960:Receptors, Estrogen / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000008:administration & dosage; D013876:Thiophenes / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D018931:Antineoplastic Agents, Hormonal; D010880:Piperidines; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; D013629:Tamoxifen; C115121:LY 353381; D005472:Fluorouracil; D008727:Methotrexate