The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer.
OBJECTIVE
We previously identified three genes, HOXB13, IL17BR and CHDH, and the HOXB13:IL17BR ratio index in particular, that strongly predicted clinical outcome in breast cancer patients receiving tamoxifen monotherapy. Confirmation in larger independent patient cohorts was needed to fully validate their clinical utility.


METHODS
Expression of HOXB13, IL17BR, CHDH, estrogen receptor (ER) and progesterone receptor (PR) were quantified by real-time polymerase chain reaction in 852 formalin-fixed, paraffin-embedded primary breast cancers from 566 untreated and 286 tamoxifen-treated breast cancer patients. Gene expression and clinical variables were analyzed for association with relapse-free survival (RFS) by Cox proportional hazards regression models.


RESULTS
ER and PR mRNA measurements were in close agreement with immunohistochemistry. In the entire cohort, expression of HOXB13 was associated with shorter RFS (P = .008), and expression of IL17BR and CHDH was associated with longer RFS (P < .0001 for IL17BR and P = .0002 for CHDH). In ER+ patients, the HOXB13:IL17BR index predicted clinical outcome independently of treatment, but more strongly in node-negative patients. In multivariate analysis of the ER+ node-negative subgroup including age, PR status, tumor size, S phase fraction, and tamoxifen treatment, the two-gene index remained a significant predictor of RFS (hazard ratio = 3.9; 95% CI, 1.5 to 10.3; P = .007).


CONCLUSIONS
This tumor bank study demonstrated HOXB13:IL17BR index is a strong independent prognostic factor for ER+ node-negative patients irrespective of tamoxifen therapy.
Ma
Xiao-Jun
XJ
AviaraDx Inc, Carlsbad, CA, USA.
Hilsenbeck
Susan G
SG
Wang
Wilson
W
Ding
Li
L
Sgroi
Dennis C
DC
Bender
Richard A
RA
Osborne
C Kent
CK
Allred
D Craig
DC
Erlander
Mark G
MG
D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D050545:Choline Dehydrogenase / Q000096:biosynthesis; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics*; D053722:Receptors, Interleukin-17; D011980:Receptors, Progesterone / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; C408922:IL17RB protein, human; D011960:Receptors, Estrogen; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011980:Receptors, Progesterone; D013629:Tamoxifen; D050545:Choline Dehydrogenase