The effect of 3-week tamoxifen treatment on oestrogen receptor levels in primary breast tumours: a flow cytometric study

Br J Cancer. 1998 May;77(10):1657-60. doi: 10.1038/bjc.1998.272.

Abstract

The effect of 3-week, preoperative tamoxifen treatment on oestrogen receptor (ER) levels, expressed by primary breast tumours, was examined. Patients (age-matched) with breast cancer, confirmed by fine-needle aspiration, were either treated with 20 mg ml(-1) oral tamoxifen per day or received no medication in the 3-week interval between assessment and surgery. Quantification of ER using flow cytometry was performed on the surgically removed tumour samples from tamoxifen-treated (n = 40) and control (n = 38, untreated) patient groups. The tumours were mechanically disaggregated, and saponin treatment rendered these cells permeable to antibodies. Using dual-parameter labelling with a FITC-conjugated antibody (NCL-5D3) directed against cytokeratin 8/18/19 and a biotinylated antibody (DAKO-ER 1D5) directed against the oestrogen receptor, ER quantification was determined on a number of receptors per cell basis. Using QC quantum bead standards, ER levels in the epithelial cell population, the non-epithelial cell population and the whole-cell population (ER+) were calculated. ER levels were significantly lower in the total cell population than tamoxifen-treated patients (P = 0.002) when compared with the control (untreated) group. By using a gating procedure using 5D3 antibody positivity, a significantly lower level was detected on examining the cytokeratin-positive population alone (P = 0.006). Using a complementary gating technique, ER levels were quantified in the cytokeratin-negative cell population. Examination of this group of cells showed no significant difference between the levels of oestrogen receptor found in the tamoxifen-treated and untreated groups (P = 0.4). We have demonstrated that ER levels can be monitored by flow cytometry. ER levels in patients treated with tamoxifen 3 weeks before operation are significantly lower than in a comparative group of patients who received no drug. Furthermore, the most significant difference in receptor levels is seen by quantification of total ER levels expressed by all the tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Estrogen Antagonists / pharmacology
  • Evaluation Studies as Topic
  • Flow Cytometry*
  • Humans
  • Receptors, Estrogen / metabolism*
  • Tamoxifen / administration & dosage
  • Tamoxifen / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Hormonal
  • Estrogen Antagonists
  • Receptors, Estrogen
  • Tamoxifen