TY - JOUR
T1 - Increased 5α-Reductase Type 2 Expression in Human Breast Carcinoma following Aromatase Inhibitor Therapy
T2 - The Correlation with Decreased Tumor Cell Proliferation
AU - Chanplakorn, Niramol
AU - Chanplakorn, Pongsthorn
AU - Suzuki, Takashi
AU - Ono, Katsuhiko
AU - Wang, Lin
AU - Chan, Monica S.M.
AU - Wing, Loo
AU - Yiu, Christopher C.P.
AU - Wing-Cheong Chow, Louis
AU - Sasano, Hironobu
N1 - Funding Information:
Disclosures/Conflicts of interest Dr. Hironobu Sasano has received the educational research grant from Novartis Oncology Japan and Pfizer Oncology Japan.
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - 5α-reductase
KW - Androgen
KW - Androgen receptor
KW - Aromatase inhibitor
KW - Breast cancer
KW - Ki67
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U2 - 10.1007/s12672-010-0062-2
DO - 10.1007/s12672-010-0062-2
M3 - Article
C2 - 21761341
AN - SCOPUS:78751580474
VL - 2
SP - 73
EP - 81
JO - Hormones and Cancer
JF - Hormones and Cancer
SN - 1868-8497
IS - 1
ER -