Biomarker Associations with Efficacy of Abiraterone Acetate and Exemestane in Postmenopausal Patients with Estrogen Receptor-Positive Metastatic Breast Cancer

• Published in: Clinical cancer research 2016-12, Vol.22 (24), p.6002-6009
• Main Authors: Li, Weimin, O'Shaughnessy, Joyce, Hayes, Daniel, Campone, Mario, Bondarenko, Igor, Zbarskaya, Irina, Brain, Etienne, Stenina, Marina, Ivanova, Olga, Graas, Marie-Pascale, Neven, Patrick, Ricci, Deborah, Griffin, Thomas, Kheoh, Thian, Yu, Margaret, Gormley, Michael, Martin, Jason, Schaffer, Michael, Zelinsky, Kathy, De Porre, Peter, Johnston, Stephen R D
• Format: Article
• Language: English
• Subjects: Abiraterone Acetate - therapeutic use; Adult; Aged; Aged, 80 and over; Androstadienes - therapeutic use; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - metabolism; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Disease-Free Survival; Female; Humans; Ki-67 Antigen - metabolism; Middle Aged; Neoplastic Cells, Circulating - drug effects; Neoplastic Cells, Circulating - metabolism; Postmenopause - metabolism; Receptors, Androgen - metabolism; Receptors, Estrogen - metabolism; Steroid 17-alpha-Hydroxylase - metabolism
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-15-2452

Abiraterone may suppress androgens that stimulate breast cancer growth. We conducted a biomarker analysis of circulating tumor cells (CTCs), formalin-fixed paraffin-embedded tissues (FFPETs), and serum samples from postmenopausal estrogen receptor (ER) breast cancer patients to identify subgroups with differential abiraterone sensitivity. Patients (randomized 1:1:1) were treated with 1,000 mg/d abiraterone acetate + 5 mg/d prednisone (AA), AA + 25 mg/d exemestane (AAE), or exemestane. The biomarker population included treated patients (n = 293). The CTC population included patients with ≥3 baseline CTCs (n = 104). Biomarker [e.g., androgen receptor (AR), ER, Ki-67, CYP17] expression was evaluated. Cox regression stratified by prior therapies in the metastatic setting (0/1 vs. 2) and setting of letrozole/anastrozole (adjuvant vs. metastatic) was used to assess biomarker associations with progression-free survival (PFS). Serum testosterone and estrogen levels were lowered and progesterone increased with AA. Baseline AR or ER expression was not associated with PFS in CTCs or FFPETs for AAE versus exemestane, but dual positivity of AR and ER expression was associated with improved PFS [HR, 0.41; 95% confidence interval (CI), 0.16-1.07; P = 0.070]. For AR expression in FFPETs obtained