17ß-Hydroxysteroid dehydrogenase type 1 as predictor of tamoxifen response in premenopausal breast cancer

Abstract 

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.

Keywords: Breast cancer, 17ß-Hydroxysteroid dehydrogenases, HSD17B1, Tamoxifen, Predictive marker, Treatment prediction, Oestrogens, Premenopausal women