Prognostic significance of Ki-67 labeling index after short-term presurgical tamoxifen in women with ER-positive breast cancer

Ann Oncol. 2011 Mar;22(3):582-587. doi: 10.1093/annonc/mdq427. Epub 2010 Aug 17.

Abstract

Background: Studies have shown that Ki-67 response after short-term neoadjuvant aromatase inhibitors may predict recurrence in postmenopausal breast cancer, whereas its prognostic effect in premenopausal women is unknown.

Patients and methods: We compared the prognostic and predictive value of baseline and post-treatment Ki-67 in 120 pre- and postmenopausal women with early-stage estrogen receptor-positive breast cancer who participated in a 4-week presurgical trial of tamoxifen.

Results: After 7.2 years of follow-up, women with post-treatment Ki-67 in the second (14%-19%), third (20%-29%) and top (≥30%) quartiles had a recurrence hazard ratio of 2.92 [95% confidence interval (CI) 0.95-8.96], 4.37 (1.56-12.25) and 6.05 (2.07-17.65), respectively, as compared with those in the bottom quartile (<14%) (P-trend = 0.001). The risk of invasive disease recurrence was 2.2% (95% CI 0.9-5.0) per point increase in baseline Ki-67 (P-trend = 0.076) and 5.0% (95% CI 2.3-7.7) per point increase in post-tamoxifen Ki-67 (P-trend < 0.001). The risk of death was 5.5 (95% CI 1.26-23.16) times higher in patients with post-drug Ki-67 ≥20% than in those with Ki-67 <20% (P-trend = 0.006).

Conclusions: Ki-67 response after short-term neoadjuvant tamoxifen is a good predictor of recurrence-free survival and overall survival, further supporting its use as surrogate biomarker to personalize adjuvant treatment and to screen novel drugs cost-effectively.

Publication types

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

MeSH terms

  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism*
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / pathology*
  • Neoplasms, Hormone-Dependent / surgery
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism
  • Staining and Labeling
  • Tamoxifen / therapeutic use*
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • ERBB2 protein, human
  • Receptor, ErbB-2