Human 3β‐hydroxysteroid dehydrogenase type 1 in human breast cancer: clinical significance and prognostic associations

Active sex steroids including estrogens and androgens are locally produced from circulating inactive steroids by various steroid-metabolizing enzymes, and play pivotal roles in the progression of hormone-dependent breast cancers. Human 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD type 1) is a critical enzyme in the formation of all classes of active steroid hormones, and is also involved in the inactivation of potent androgen dihydrotestosterone (DHT). Therefore, this enzyme is suggested to modulate active sex steroid production or inactivation, with a role in hormone-dependent breast cancer. The purpose of this study was to investigate the clinical significance of 3β-HSD type 1 in human breast cancer. Using immunohistochemistry (IHC), we evaluated 3β-HSD type 1 expression in 161 human breast cancers and analyzed correlations of 3β-HSD type 1 expression with various clinicopathological factors. Of 161 breast cancer cases, 3β-HSD type 1 expression in cancer cells was detected in 119 cases (73.9%), and was positively correlated with estrogen receptor (ER)-positivity but not HER-2 status. In ER-positive cases (n = 130), 3β-HSD type 1 expression was inversely correlated with invasive tumor size (P = 0.0009), presence of invasive region (P = 0.0107), and lymphatic involvement (P = 0.0004). 3β-HSD type 1 expression was significantly associated with decreased risk of recurrence or improved prognosis by both univariate (P = 0.0003 and P = 0.009, respectively) and multivariate (P = 0.027 and P = 0.023, respectively) analyses. Our findings indicate that this enzyme is a prognostic factor in hormone-dependent breast cancer.