Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker

J Natl Cancer Inst. 2013 Jul 17;105(14):1036-42. doi: 10.1093/jnci/djt146. Epub 2013 Jun 28.

Abstract

Background: Biomarkers to optimize extended adjuvant endocrine therapy for women with estrogen receptor (ER)-positive breast cancer are limited. The HOXB13/IL17BR (H/I) biomarker predicts recurrence risk in ER-positive, lymph node-negative breast cancer patients. H/I was evaluated in MA.17 trial for prognostic performance for late recurrence and treatment benefit from extended adjuvant letrozole.

Methods: A prospective-retrospective, nested case-control design of 83 recurrences matched to 166 nonrecurrences from letrozole- and placebo-treated patients within MA.17 was conducted. Expression of H/I within primary tumors was determined by reverse-transcription polymerase chain reaction with a prespecified cutpoint. The predictive ability of H/I for ascertaining benefit from letrozole was determined using multivariable conditional logistic regression including standard clinicopathological factors as covariates. All statistical tests were two-sided.

Results: High H/I was statistically significantly associated with a decrease in late recurrence in patients receiving extended letrozole therapy (odds ratio [OR] = 0.35; 95% confidence interval [CI] = 0.16 to 0.75; P = .007). In an adjusted model with standard clinicopathological factors, high H/I remained statistically significantly associated with patient benefit from letrozole (OR = 0.33; 95% CI = 0.15 to 0.73; P = .006). Reduction in the absolute risk of recurrence at 5 years was 16.5% for patients with high H/I (P = .007). The interaction between H/I and letrozole treatment was statistically significant (P = .03).

Conclusions: In the absence of extended letrozole therapy, high H/I identifies a subgroup of ER-positive patients disease-free after 5 years of tamoxifen who are at risk for late recurrence. When extended endocrine therapy with letrozole is prescribed, high H/I predicts benefit from therapy and a decreased probability of late disease recurrence.

Publication types

  • 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
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Aromatase Inhibitors / administration & dosage
  • Aromatase Inhibitors / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Case-Control Studies
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Homeodomain Proteins / analysis*
  • Humans
  • Incidence
  • Letrozole
  • Logistic Models
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasm Staging
  • Nitriles / administration & dosage
  • Nitriles / therapeutic use*
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Receptor, ErbB-2 / analysis
  • Receptors, Estrogen / analysis
  • Receptors, Interleukin / analysis*
  • Receptors, Progesterone / analysis
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triazoles / administration & dosage
  • Triazoles / therapeutic use*

Substances

  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Biomarkers, Tumor
  • HOXB13 protein, human
  • Homeodomain Proteins
  • IL17RB protein, human
  • Nitriles
  • Receptors, Estrogen
  • Receptors, Interleukin
  • Receptors, Progesterone
  • Triazoles
  • Letrozole
  • ERBB2 protein, human
  • Receptor, ErbB-2