Short-term anastrozole therapy reduces Ki-67 and progesterone receptor expression in invasive breast cancer: a prospective, placebo-controlled, double-blind trial

J Cancer Res Clin Oncol. 2011 May;137(5):897-905. doi: 10.1007/s00432-010-0950-4. Epub 2010 Oct 1.

Abstract

Purpose: The objective of this study was to compare Ki-67, Bcl-2, Bax, Bak, ER, and PgR expression in postmenopausal women with ER-positive invasive breast cancer (IBC) before and after short-term hormone therapy (HT) with either tamoxifen or anastrozole in order to identify a possible biomarker profile associated with hormone resistance.

Methods: Fifty-eight patients with palpable IBC were assigned to receive neoadjuvant therapy with either anastrozole, placebo, or tamoxifen for 26 days prior to surgery. Tissue microarray blocks were constructed from pre- and post-treatment biopsy samples and used for immunohistochemical analysis. Biomarker (Ki-67, Bcl-2, Bax, Bak, ER, and PgR) levels were assessed semiquantitatively using the Allred score. A statistical analysis was performed using general estimating equations (GEE) and analysis of variance (ANOVA) with a significance level of 0.05.

Results: There was a significant reduction in PgR scores from baseline (mean, 4.22) to post-treatment (mean, 1.94) in the anastrozole group, but only a non-significant trend toward an increase in PgR scores was found in the tamoxifen group. There was a significant reduction in Ki-67 scores from baseline (mean, 3.61) to post-treatment (mean, 2.56) in the anastrozole group (P = 0.01), but only a non-significant trend toward a reduction in Ki-67 scores was found in the tamoxifen group.

Conclusions: There was a significant reduction in PgR and Ki-67 expression in the group treated with anastrozole. In the present study, the short-term HT was not associated with changes in apoptosis-related protein levels, regardless the type of drug used.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anastrozole
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Aromatase Inhibitors / therapeutic use*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Double-Blind Method
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis*
  • Middle Aged
  • Nitriles / therapeutic use*
  • Prospective Studies
  • Receptors, Progesterone / analysis*
  • Tamoxifen / therapeutic use
  • Triazoles / therapeutic use*

Substances

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Ki-67 Antigen
  • Nitriles
  • Receptors, Progesterone
  • Triazoles
  • Tamoxifen
  • Anastrozole