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Clin Cancer Res. 2010 Apr 1;16(7):2176-86. doi: 10.1158/1078-0432.CCR-09-1859. Epub 2010 Mar 23.

Effect of low-dose tamoxifen on steroid receptor coactivator 3/amplified in breast cancer 1 in normal and malignant human breast tissue.

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1
Institute of Medicine, University of Bergen, Hormone Laboratory, Haukeland University Hospital, Bergen, Norway.

Erratum in

  • Clin Cancer Res. 2010 Oct 15;16(20):5087. De Censi, Andrea [corrected to DeCensi, Andrea].

Abstract

PURPOSE:

Nuclear receptor coactivator expression and activity may partly explain the complex agonist/antagonist effects of tamoxifen at clinical level. In a preoperative trial, dose reduction from 20 to 1 mg tamoxifen was associated with retained antiproliferative effect on breast cancer. Here, we assessed the gene expression of the steroid receptor coactivators SRC-1, SRC-2/transcription intermediary factor 2, and SRC-3/amplified in breast cancer 1 (AIB1) and the growth factor receptor HER-2/neu under three tamoxifen dose regimens.

EXPERIMENTAL DESIGN:

Surgical specimens from estrogen receptor-positive breast cancer and adjacent normal breast tissue from 64 patients treated 4 weeks preoperatively with 20, 5, or 1 mg/d tamoxifen and 28 nontreated breast cancer controls were analyzed for coactivator and HER-2/neu mRNA expression using real-time reverse transcription-PCR. The gene expression levels were related to immunohistochemical expression of Ki67, serum levels of insulin-like growth factor I and sex hormone binding globulin, other prognostic factors, and clinical outcome.

RESULTS:

The coactivators and HER-2/neu mRNA levels were higher in malignant compared with normal tissue (P < 0.001). Tamoxifen significantly increased the expression of coactivators in normal and malignant tissue irrespective of dose, especially for SRC-3/AIB1 (P < 0.001 tamoxifen-treated versus nontreated subjects). SRC-3/AIB1 and HER-2/neu mRNA levels were positively correlated (P = 0.016), but the coactivators could not explain the variability of Ki67, insulin-like growth factor I, and sex hormone binding. Although not significant, SRC-3/AIB1 tended to be higher in subjects with poor clinical outcome and unfavorable prognostic factors.

CONCLUSIONS:

Increased coactivator mRNA levels seem to be an early response to tamoxifen without dose-response relationship in the 1- to 20-mg range. Clinical and molecular effects of low-dose tamoxifen should be further explored.

PMID:
20332317
DOI:
10.1158/1078-0432.CCR-09-1859
[Indexed for MEDLINE]
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