5α-reductase type 3 is a predictive marker for chemotherapy efficacy in breast cancer in an androgen-independent manner

Abstract

Breast cancer is one of the most representative sex-steroid-dependent cancers and both estrogens and androgens are locally synthesized in breast cancer tissues by sex-steroid producing enzymes. 5$\alpha$-reductase (5$\alpha$-Red) is an enzyme which reduces testosterone to biologically active dihydrotestosterone (DHT), serving as a regulator of intratumoral DHT levels. To date, three 5$\alpha$-Red isozymes have been identified: 5$\alpha$-Red types 1–3. However, 5$\alpha$-Red type 3 is not fully examined in breast cancer, and its contribution to DHT synthesis is yet to be elucidated. We therefore immunolocalized 5$\alpha$-Red type 3 in breast cancer tissues and correlated its immunoreactivity with intratumoral DHT levels as well as clinicopathological parameters. In the present study, 5$\alpha$-Red type 3 immunoreactivity was not correlated with intratumoral DHT level. Additionally, the immunoreactivity of 5$\alpha$-Red type 3 was negatively correlated with that of 17$\beta$-hydroxysteroid dehydrogenase type 5, which converts androstenedione to testosterone. In the prognostic analysis, although 5$\alpha$-Red type 3 immunoreactivity was not correlated with patients’ clinical outcomes in the entire cohort of 172 breast cancer cases, it was significantly correlated with better clinical outcomes in the patients with non-luminal A type breast cancer or in those who received chemotherapy. These findings suggest that 5$\alpha$-Red type 3 does not contribute to intratumoral DHT synthesis, while served as a potent predictive marker for efficacy of chemotherapy in breast cancer independent of androgen action.