HOXB13-to-IL17BR expression ratio is related with tumor aggressiveness and response to tamoxifen of recurrent breast cancer: a retrospective study.
OBJECTIVE
A HOXB13-to-IL17BR expression ratio was previously identified to predict clinical outcome of breast cancer patients treated with adjuvant tamoxifen. However, this ratio may predict a tumor's response to tamoxifen, its intrinsic aggressiveness, or both.


METHODS
We have measured the HOXB13 and IL17BR expression levels by real-time polymerase chain reaction in 1,252 primary breast tumor specimens. Expression levels were normalized to housekeeper gene levels and related to clinicopathologic factors for all patients. The primary objective of this study was to determine the relationship of a HOXB13-to-IL17BR ratio with tumor aggressiveness and/or with response to tamoxifen therapy in estrogen receptor (ER) -positive disease. We selected ER-positive tumors, and clinical end points for the HOXB13-to-IL17BR ratio were disease-free survival (DFS) in patients with primary breast cancer (N = 619) and progression-free survival (PFS) in patients with recurrent breast cancer treated with first-line tamoxifen monotherapy (N = 193). The odds ratio (OR) and hazard ratio (HR) and their 95% CI were calculated, and all P values were two-sided.


RESULTS
The HOXB13-to-IL17BR ratio was significantly associated with DFS and PFS. In multivariate analysis, HOXB13-to-IL17BR ratio expression levels were associated with a shorter DFS for node-negative patients only. Corrected for traditional predictive factors, the dichotomized HOXB13-to-IL17BR ratio was the strongest predictor in multivariate analysis for a poor response to tamoxifen therapy (OR = 0.16; 95% CI, 0.06 to 0.45; P < .001) and a shorter PFS (HR = 2.97; 95% CI, 1.82 to 4.86; P < .001).


CONCLUSIONS
High HOXB13-to-IL17BR ratio expression levels associate with both tumor aggressiveness and tamoxifen therapy failure.
Jansen
Maurice P H M
MP
Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. m.p.h.m.jansen@erasmusmc.nl
Sieuwerts
Anieta M
AM
Look
Maxime P
MP
Ritstier
Kirsten
K
Meijer-van Gelder
Marion E
ME
van Staveren
Iris L
IL
Klijn
Jan G M
JG
Foekens
John A
JA
Berns
Els M J J
EM
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000378:metabolism*; D053722:Receptors, Interleukin-17; D012016:Reference Values; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D013629:Tamoxifen / Q000008:administration & dosage*
C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; C408922:IL17RB protein, human; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D013629:Tamoxifen