Microsomal epoxide hydrolase expression as a predictor of tamoxifen response in primary breast cancer: a retrospective exploratory study with long-term follow-up.
OBJECTIVE
It has been suggested that estrogen receptor-independent high-affinity binding sites for antiestrogens could limit their local bioavailability and response. Microsomal epoxide hydrolase (mEH) was recently shown to be a component of the antiestrogen binding site complex. We investigated whether mEH expression in primary breast tumors is related to disease outcome and to the efficacy of tamoxifen treatment.


METHODS
Expression of mEH was semiquantitatively assessed by immunohistochemistry in sections prepared from archival paraffin blocks of primary breast cancers from 179 patients with a mean follow-up time of 81 months.


RESULTS
Expression of mEH was correlated with poor disease outcome in all patients (P: < .01; n = 179) and in patients receiving tamoxifen (P: < .01; n = 78), but not in patients not treated with tamoxifen. Moreover, mEH was an independent prognostic factor by Cox regression analysis.


CONCLUSIONS
The results of this first exploratory study suggest that mEH expression in primary breast cancer could be of predictive value for response to tamoxifen treatment and/or may be a novel independent prognostic factor for survival. The results are in agreement with the model that mEH participates in an estrogen receptor-independent tamoxifen- binding complex.
Fritz
P
P
Center of Diagnostic Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany.
Mürdter
T E
TE
Eichelbaum
M
M
Siegle
I
I
Weissert
M
M
Zanger
U M
UM
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D004851:Epoxide Hydrolases / Q000378:metabolism*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D013629:Tamoxifen / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D013629:Tamoxifen; D004851:Epoxide Hydrolases