Predictive relevance of HOXB13 protein expression for tamoxifen benefit in breast cancer.
BACKGROUND
The HOXB13:IL17BR index has been identified to predict clinical outcome in the setting of adjuvant tamoxifen monotherapy of breast cancer. Further studies have shown that HOXB13 in particular can indicate benefit of prolonged tamoxifen treatment. Patients with high-expressing tumors did not benefit from prolonged treatment, suggesting that HOXB13 might be involved in tamoxifen resistance. No studies have been made regarding the HOXB13 protein levels in breast cancer. The aim of our study was to investigate whether tamoxifen benefit can be correlated to different levels of HOXB13 protein expression.


METHODS
We used immunohistochemistry to analyze protein levels of HOXB13 in tumor samples from 912 postmenopausal node-negative breast cancer patients randomized to adjuvant tamoxifen therapy or no endocrine treatment.


RESULTS
Tamoxifen-treated patients with estrogen receptor-positive tumors expressing none or low levels of HOXB13 had a clear benefit from tamoxifen in terms of longer distant recurrence-free survival (DRFS) (hazard ratio = 0.38, 95% confidence interval = 0.23 to 0.60, P = 0.000048). However, for patients with a high or intermediate HOXB13 tumor expression, tamoxifen did not prolong the DRFS compared with the untreated patients (hazard ratio = 0.88, 95% confidence interval = 0.47 to 1.65, P = 0.69). Interaction between HOXB13 expression and benefit from tamoxifen was statistically significant for DRFS (P = 0.035). No prognostic value could be ascribed to HOXB13 among systemically untreated patients.


CONCLUSIONS
A high HOXB13 expression was associated with decreased benefit from tamoxifen, which indicates that HOXB13 protein level may be used as a predictive marker for tamoxifen treatment.
Jerevall
Piiha-Lotta
PL
Department of Clinical and Experimental Medicine, Division of Oncology, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden. piiha-lotta.jerevall@liu.se
Jansson
Agneta
A
Fornander
Tommy
T
Skoog
Lambert
L
Nordenskjöld
Bo
B
Stål
Olle
O
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D017698:Postmenopause; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D013548:Sweden; D013629:Tamoxifen / Q000627:therapeutic use*; D046888:Tissue Array Analysis; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; D013629:Tamoxifen