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Increased 5α-reductase type 2 expression in human breast carcinoma following aromatase inhibitor therapy : the correlation with decreased tumor cell proliferation . Tumor cell proliferation and progression of breast cancer are influenced by female sex steroids . However , not all breast cancer patients respond to aromatase inhibitors ( AI ) , and many patients become unresponsive or relapse . Recent studies demonstrate that not only estrogens but also androgens may serve as regulators of estrogen-responsive as well as estrogen-unresponsive human breast cancers . However , the mechanism underlying these androgenic actions has remained relatively unknown . Therefore , in this study , we evaluated the effects of AI upon the expression of enzymes involved in intratumoral androgen production including 17β-hydroxysteroid dehydrogenase type 5 ( 17βHSD5 ) , 5α-reductase types 1 and 2 ( 5αRed1 and 5αRed2 ) as well as androgen receptor ( AR ) levels and correlated the findings with therapeutic responses including Ki67 labeling index ( Ki67 ) . Eighty-two postmenopausal invasive ductal carcinoma patients were enrolled in CAAN study from November 2001 to April 2004 . Pre- and post-treatment specimens of 29 cases were available for this study . The status of 17βHSD5 , 5αRed1 , 5αRed2 , and Ki67 in pre- and post-treatment specimens were evaluated . The significant increments of 5αRed2 as well as AR were detected in biological response group whose Ki67 LI decreased by more than 40 % of the pre-treatment level . This is the first study demonstrating an increment of 5αRed2 and AR in the group of the patients associated with Ki67 decrement following AI treatment . These results suggest that increased 5αRed2 and AR following AI treatment may partly contribute to reduce the tumor cell proliferation through increasing intratumoral androgen concentrations and its receptor .