17β-Hydroxysteroid dehydrogenase 1:2 and breast cancer recurrence:a Danish population-based study

BACKGROUND: Approximately 20–40% of patients diagnosed with breast cancer will experience a recurrence up to 20 years after their original diagnosis. 17?-hydroxysteroid dehydrogenase 1 and 2 (HSD17B1 and HSD17B2, respectively) regulate intratumoral concentrations of oestradiol, which promotes growth and proliferation of hormone dependent tumours. Breast carcinomas with increased HSD17B1, without a corresponding increase in HSD17B2, expression may become resistant to tamoxifen therapy by producing locally higher concentrations of oestradiol, which compete with tamoxifen and its metabolites for binding to the oestrogen receptor (ER). MATERIALS AND METHODS: In this population-based case-control study, we included women diagnosed with stage I–III breast cancer between 1985 and 2001, aged 35–69 years, registered in the Danish Breast Cancer Group. We identified 541 cases of breast cancer recurrence among women with ER positive disease who were treated with tamoxifen for at least 1 year (ER+TAM+). We also enrolled 300 breast cancer recurrence cases among women with ER negative disease, not treated with tamoxifen, who survived at least 1 year (ER?/TAM?). Controls were recurrence-free breast cancer patients at the time of case diagnosis, matched to recurrence cases on ER/TAM status, date of surgery, menopausal status, stage, and county or residence. Expression of HSD17B1 and HSD17B2 were measured by immunohistochemistry on tissue microarrays. We fit logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs) associating the HSD17B1:HSD17B2 ratio (>1 vs. ?1)—and each enzyme’s independent expression—with recurrence. RESULTS: We found no association between the HSD17B1:HSD17B2 ratio and breast cancer recurrence in either ER/TAM stratum (ER+/TAM+: OR=1.03, 95% CI: 0.78, 1.40; ER?/TAM?: OR=1.02, 95% CI: 0.77, 1.19). Associations for expression of each individual enzyme were also near null. CONCLUSION: The ratio of HSD17B1 expression to HSD17B2 expression was not associated with breast cancer recurrence in this study.