A two-gene expression ratio of homeobox 13 and interleukin-17B receptor for prediction of recurrence and survival in women receiving adjuvant tamoxifen.
OBJECTIVE
In the adjuvant treatment of estrogen receptor (ER)-positive breast cancer, additional markers are needed to identify women at high risk for recurrence.


METHODS
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.


CONCLUSIONS
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.
Goetz
Matthew P
MP
Department of Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. goetz.matthew@mayo.edu
Suman
Vera J
VJ
Ingle
James N
JN
Nibbe
Andrea M
AM
Visscher
Dan W
DW
Reynolds
Carol A
CA
Lingle
Wilma L
WL
Erlander
Mark
M
Ma
Xiao-Jun
XJ
Sgroi
Dennis C
DC
Perez
Edith A
EA
Couch
Fergus J
FJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000235:genetics*; D053722:Receptors, Interleukin-17; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D005819:Genetic Markers; C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; C408922:IL17RB protein, human; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D013629:Tamoxifen