Analysis of Ki-67 expression with neoadjuvant anastrozole or tamoxifen in patients receiving goserelin for premenopausal breast cancer

Cancer. 2013 Feb 15;119(4):704-13. doi: 10.1002/cncr.27818. Epub 2012 Sep 12.

Abstract

Background: The increasing costs associated with large-scale adjuvant trials mean that the prognostic value of biologic markers is increasingly important. The expression of nuclear antigen Ki-67, a marker of cell proliferation, has been correlated with treatment efficacy and is being investigated for its value as a predictive marker of therapeutic response. In the current study, the authors explored correlations between Ki-67 expression and tumor response, estrogen receptor (ER) status, progesterone receptor (PgR) status, and histopathologic response from the STAGE study (S_tudy of T_amoxifen or A_rimidex, combined with G_oserelin acetate to compare E_fficacy and safety).

Methods: In a phase 3, double-blind, randomized trial (National Clinical Trials identifier NCT00605267), premenopausal women with ER-positive, early stage breast cancer received either anastrozole plus goserelin or tamoxifen plus goserelin for 24 weeks before surgery. The Ki-67 index, hormone receptor (ER and PgR) status, and histopathologic responses were determined from histopathologic samples that were obtained from core-needle biopsies at baseline and at surgery. Tumor response was determined by using magnetic resonance imaging or computed tomography.

Results: In total, 197 patients were randomized to receive either anastrozole plus goserelin (n = 98) or tamoxifen plus goserelin (n = 99). The best overall tumor response was better for the anastrozole group compared with the tamoxifen group both among patients who had a baseline Ki-67 index ≥20% and among those who had a baseline Ki-67 index <20%. There was no apparent correlation between baseline ER status and the Ki-67 index in either group. Positive PgR status was reduced from baseline to week 24 in the anastrozole group.

Conclusions: In premenopausal women with ER-positive breast cancer, anastrozole produced a greater best overall tumor response compared with tamoxifen regardless of the baseline Ki-67 index.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anastrozole
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / surgery
  • Double-Blind Method
  • Female
  • Goserelin / administration & dosage
  • Goserelin / therapeutic use
  • Humans
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism*
  • Middle Aged
  • Neoadjuvant Therapy
  • Nitriles / administration & dosage
  • Nitriles / therapeutic use
  • Predictive Value of Tests
  • Premenopause
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Tamoxifen / administration & dosage
  • Tamoxifen / therapeutic use
  • Treatment Outcome
  • Triazoles / administration & dosage
  • Triazoles / therapeutic use

Substances

  • Antineoplastic Agents, Hormonal
  • Ki-67 Antigen
  • Nitriles
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Triazoles
  • Tamoxifen
  • Goserelin
  • Anastrozole