Breast Cancer Research and Treatment

, Volume 135, Issue 2, pp 619–627

Ki67 expression in the primary tumor predicts for clinical benefit and time to progression on first-line endocrine therapy in estrogen receptor-positive metastatic breast cancer

  • Y. Delpech
  • Y. Wu
  • K. R. Hess
  • L. Hsu
  • M. Ayers
  • R. Natowicz
  • C. Coutant
  • R. Rouzier
  • E. Barranger
  • G. N. Hortobagyi
  • D. Mauro
  • L. Pusztai
Brief Report

DOI: 10.1007/s10549-012-2194-2

Cite this article as:
Delpech, Y., Wu, Y., Hess, K.R. et al. Breast Cancer Res Treat (2012) 135: 619. doi:10.1007/s10549-012-2194-2

Abstract

We examined whether baseline Ki67 expression in estrogen receptor-positive (ER+) primary breast cancer correlates with clinical benefit and time to progression on first-line endocrine therapy and survival in metastatic disease. Ki67 values and outcome information were retrieved from a prospectively maintained clinical database and validated against the medical records; 241 patients with metastatic breast cancer were included—who had ER+ primary cancer with known Ki67 expression level—and received first-line endocrine therapy for metastatic disease. Patients were assigned to low (<10 %), intermediate (10–25 %), or high (>25 %) Ki67 expression groups. Kaplan–Meier survival curves were plotted and multivariate analysis was performed to assess association between clinical and immunohistochemical variables and outcome. The clinical benefit rates were 81, 65, and 55 % in the low (n = 32), intermediate (n = 103), and high (n = 106) Ki67 expression groups (P = 0.001). The median times to progression on first-line endocrine therapy were 20.3 (95 % CI, 17.5–38.5), 10.8 (95 % CI, 8.9–18.8), and 8 (95 % CI, 6.1–11.1) months, respectively (P = 0.0002). The median survival times after diagnosis of metastatic disease were also longer for the low/intermediate compared to the high Ki67 group, 52 versus 30 months (P < 0.0001). In multivariate analysis, high Ki67 expression in the primary tumor remained an independent adverse prognostic factor in metastatic disease (P = 0.001). Low Ki67 expression in the primary tumor is associated with higher clinical benefit and longer time to progression on first-line endocrine therapy and longer survival after metastatic recurrence.

Keywords

Ki67Clinical benefitEndocrine therapyMetastatic breast cancerSurvivalTime to progression

Supplementary material

10549_2012_2194_MOESM1_ESM.docx (15 kb)
Supplementary Table 1. Clinical benefit rates by Ki67 group for patients who presented with stage I-III disease at diagnosis. (DOCX 15 kb)
10549_2012_2194_MOESM2_ESM.tif (848 kb)
Supplementary Figure 1. Survival after metastasis (A) and time to progression on first-line endocrine therapy for metastatic disease (B) in low (Ki67 < 10 %), intermediate (Ki67 10-25 %) and high (Ki67 > 25 %) proliferation groups for patients who first presented with stage I-III breast cancer. Ki67 levels were determined in the primary cancer. (TIFF 847 kb)

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Y. Delpech
    • 1
    • 2
    • 3
  • Y. Wu
    • 4
  • K. R. Hess
    • 5
  • L. Hsu
    • 1
  • M. Ayers
    • 6
  • R. Natowicz
    • 1
    • 7
  • C. Coutant
    • 8
    • 9
  • R. Rouzier
    • 10
    • 11
  • E. Barranger
    • 2
    • 3
  • G. N. Hortobagyi
    • 1
  • D. Mauro
    • 6
  • L. Pusztai
    • 1
  1. 1.Department of Breast Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Gynecology and ObstetricsLariboisiere Hospital/AP-HPParisFrance
  3. 3.The University Denis DiderotParis 7France
  4. 4.Department of PathologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Department of BiostatisticsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Merck & Co., Inc.Whitehouse StationUSA
  7. 7.ESIEE-PARISUniversity of Paris-EstNoisy le GrandFrance
  8. 8.Department of Surgical OncologyGeorges Francois Leclerc Cancer CenterDijonFrance
  9. 9.The University of BourgogneDijonFrance
  10. 10.Department of Gynecology and ObstetricsTenon Hospital/AP-HPParisFrance
  11. 11.The University Pierre and Marie CurieParis 6France