17ss-Hydroxysteroid
dehydrogenases (17HSDs) are involved in the local regulation of sex
steroids.
17HSD1 converts oestrone (E1) to the more potent
oestradiol (E2) and 17HSD2 catalyses the reverse reaction. The aim of this study was to investigate the expression of these
enzymes in premenopausal breast
cancers and to analyse if they have any prognostic or
tamoxifen predictive value. Premenopausal patients with invasive
breast cancer, stage II (UICC), were randomised to either 2years of adjuvant
tamoxifen (n=276) or no
tamoxifen (n=288). The median follow-up was 13.9years (range 10.5-17.5). The expression of
17HSD1 and 17HSD2 was analysed with immunohistochemistry using tissue microarrays. The
enzyme expression level (-/+/++/+++) was successfully determined in 396 and 373 tumours, respectively. Women with
hormone-receptor positive tumours, with low levels (-/+/++) of
17HSD1, had a 43% reduced risk of recurrence, when treated with
tamoxifen (Hazard Ratio (HR)=0.57; 95% confidence interval (CI), 0.37-0.86; p=0.0086). On the other hand high expression (+++) of
17HSD1 was associated with no significant difference between the two treatment arms (HR=0.91; 95% CI, 0.43-1.95; p=0.82). The interaction between
17HSD1 and
tamoxifen was significant during the first 5 years of follow-up (p=0.023). In the cohort of systemically untreated patients no prognostic importance was observed for
17HSD1. We found no predictive or prognostic value for 17HSD2. This is the first report of
17HSD1 in a cohort of premenopausal women with
breast cancer randomised to
tamoxifen. Our data suggest that
17HSD1 might be a predictive factor in this group of patients.