title: Exploring the two-gene ratio in breast cancer--independent roles for HOXB13 and IL17BR in prediction of clinical outcome.
abstract: BACKGROUND
  The two-gene expression ratio HOXB13:IL17BR has been proposed to predict the outcome of tamoxifen-treated breast cancer patients. We intended to examine whether this ratio can predict the benefit of 5 years vs. 2 years of tamoxifen treatment of postmenopausal patients. A further objective was to investigate any prognostic effects of the ratio in systematically untreated premenopausal patients. Based on the current knowledge of HOXB13 and IL17BR, we hypothesized that these genes may have individual prognostic or predictive power.
  
  
  METHODS
  Expression of HOXB13 and IL17BR were quantified by real-time PCR in tumors from 264 randomized postmenopausal patients and 93 systemically untreated premenopausal patients.
  
  
  RESULTS
  A high HOXB13:IL17BR ratio was associated with aggressive tumor characteristics, as were low levels of IL17BR alone. The ratio and HOXB13 alone predicted recurrence-free survival after endocrine treatment, with a benefit of prolonged treatment in estrogen receptor-positive patients correlated to a low ratio (recurrence rate ratio: RR = 0.39; P = 0.030), or low expression of HOXB13 (RR = 0.37; P = 0.015). No difference in recurrence-free survival was seen for the high ratio or high HOXB13 subgroups. The predictive value of HOXB13 and HOXB13:IL17BR was significant in multivariate analysis. In the systemically untreated cohort, only IL17BR showed independent prognostic significance.
  
  
  CONCLUSIONS
  We conclude that the ratio or HOXB13 alone can predict the benefit of endocrine therapy, with a high ratio or a high expression rendering patients less likely to respond. We have also shown that IL17BR might be an independent prognostic factor in breast cancer.
authors: Department of Biomedicine and Surgery, Division of Oncology, Linköping University, Linköping, Sweden. piiha-lotta.Jerevall@ibk.liu.se
authors: Piiha-Lotta
authors: PL
authors: Jerevall
authors: Sara
authors: S
authors: Brommesson
authors: Carina
authors: C
authors: Strand
authors: Sofia
authors: S
authors: Gruvberger-Saal
authors: Per
authors: P
authors: Malmström
authors: Bo
authors: B
authors: Nordenskjöld
authors: Sten
authors: S
authors: Wingren
authors: Peter
authors: P
authors: Söderkvist
authors: Mårten
authors: M
authors: Fernö
authors: Olle
authors: O
authors: Stål
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017698:Postmenopause; D017697:Premenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D053722:Receptors, Interleukin-17; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; C408922:IL17RB protein, human; D011960:Receptors, Estrogen; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D013629:Tamoxifen