Rui Huang1,2,3, Jiguang Han1, Xiaoshuan Liang1, Shanshan Sun1, Yongdong Jiang1, Bingshu Xia1, Ming Niu1, Dalin Li1, Jian Zhang1, Shuo Wang1, Wei Wei1, Qing Liu1, Wei Zheng1, Guoqiang Zhang1, Yanni Song1,3,4,5, Da Panga1,3,6,7. 1. Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China. 2. Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. 3. Heilongjiang Academy of Medical Sciences, Harbin, China. 4. Department of Plastic and Cosmetic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. 5. Department of Pathology, Tianjin Medical University Cancer Hospital, Tianjin, China. 6. Sino-Russian Medical Research Center, Heilongjiang Academy of Medical Sciences, Harbin, China. 7. Northern China Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin, China.
Abstract
BACKGROUND/AIMS: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment. METHODS: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer. RESULTS: AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/β-catenin signaling and inhibited the growth of AR+/ER- breast cancer. CONCLUSION: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.
BACKGROUND/AIMS: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment. METHODS: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer. RESULTS:AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/β-catenin signaling and inhibited the growth of AR+/ER- breast cancer. CONCLUSION: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.
Authors: Rosalind P Candelaria; Beatriz E Adrada; Wei Wei; Alastair M Thompson; Lumarie Santiago; Deanna L Lane; Monica L Huang; Elsa M Arribas; Gaiane M Rauch; W Fraser Symmans; Michael Z Gilcrease; Lei Huo; Bora Lim; Naoto T Ueno; Stacy L Moulder; Wei Tse Yang Journal: Eur J Radiol Date: 2019-03-21 Impact factor: 3.528
Authors: Pia Giovannelli; Marzia Di Donato; Giovanni Galasso; Erika Di Zazzo; Antonio Bilancio; Antimo Migliaccio Journal: Front Endocrinol (Lausanne) Date: 2018-08-28 Impact factor: 5.555
Authors: Marta Ávalos-Moreno; Araceli López-Tejada; Jose L Blaya-Cánovas; Francisca E Cara-Lupiañez; Adrián González-González; Jose A Lorente; Pedro Sánchez-Rovira; Sergio Granados-Principal Journal: J Pers Med Date: 2020-10-29