A two-gene expression ratio of homeobox 13 and interleukin-17B receptor for prediction of recurrence and survival in women receiving adjuvant tamoxifen

Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2080-7. doi: 10.1158/1078-0432.CCR-05-1263.

Abstract

Purpose: In the adjuvant treatment of estrogen receptor (ER)-positive breast cancer, additional markers are needed to identify women at high risk for recurrence.

Experimental design: We examined the association between the ratio of the homeobox 13 (HOXB13) to interleukin-17B receptor (IL-17BR) expression and the clinical outcomes of relapse and survival in women with ER-positive breast cancer enrolled onto a North Central Cancer Treatment Group adjuvant tamoxifen trial (NCCTG 89-30-52).

Results: Tumor blocks were obtained from 211 of 256 eligible patients, and quantitative reverse transcription-PCR profiles for HOXB13 and IL-17BR were obtained from 206 patients. The cut point for the two-gene log 2(expression ratio) that best discriminated clinical outcome (recurrence and survival) was selected and identified women with significantly worse relapse-free survival (RFS), disease-free survival (DFS), and overall survival (OS), independent of standard prognostic markers. The cut point differed as a function of nodal status [node negative (59th percentile) versus node positive (90th percentile)]. In the node-positive cohort (n = 86), the HOXB13/IL-17BR ratio was not associated with relapse or survival. In contrast, in the node-negative cohort (n = 130), a high HOXB13/IL-17BR ratio was associated with significantly worse RFS [hazard ratio (HR), 1.98; P = 0.031], DFS (HR, 2.03; P = 0.015), and OS (HR, 2.4; P = 0.014), independent of standard prognostic markers.

Conclusion: A high HOXB13/IL-17BR expression ratio is associated with increased relapse and death in patients with resected node-negative, ER-positive breast cancer treated with tamoxifen and may identify patients in whom alternative therapies should be studied.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genetic Markers / genetics
  • Homeodomain Proteins / genetics*
  • Humans
  • Middle Aged
  • Receptors, Interleukin / genetics*
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Survival Analysis
  • Tamoxifen / administration & dosage
  • Tamoxifen / therapeutic use*

Substances

  • Antineoplastic Agents, Hormonal
  • Genetic Markers
  • HOXB13 protein, human
  • Homeodomain Proteins
  • IL17RB protein, human
  • Receptors, Interleukin
  • Tamoxifen