Li, Weimin and O'Shaughnessy, Joyce and Hayes, Daniel and Campone, Mario and Bondarenko, Igor and Zbarskaya, Irina and Brain, Etienne and Stenina, Marina and Ivanova, Olga and Graas, Marie-Pascale and Neven, Patrick and Ricci, Deborah and Griffin, Thomas and Kheoh, Thian and Yu, Margaret and Gormley, Michael and Martin, Jason and Michael, Schaffer and Zelinsky, Kathy and De Porre, Peter and Johnston, Stephen R.D. (2016) Biomarker Associations with Efficacy of Abiraterone Acetate and Exemestane in Postmenopausal Patients with Estrogen Receptor–Positive Metastatic Breast Cancer. Clinical Cancer Research, 22 (24). pp. 6002-6009. ISSN 1078-0432 (print), 1557-3265 ( online)
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Abstract
Purpose: 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)þ breast cancer patients to identify subgroups with differential abiraterone sensitivity. Methods: Patients (randomized 1:1:1) were treated with 1,000 mg/d abiraterone acetate þ 5 mg/d prednisone (AA), AA þ 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). Results: Serum testosterone and estrogenlevels werelowered 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 <1 year prior to first dose (n = 67), a trend for improved PFS was noted for AAE versus exemestane (HR, 0.56; 95% CI, 0.24–1.33; P = 0.19). Conclusions: An AA pharmacodynamic effect was shown by decreased serum androgen and estrogen levels and increased progesterone. AR and ER dual expression in CTCs and newly obtained FFPETs may predict AA sensitivity.
| Item Type: | Article |
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| Additional Information: | DOI: 10.1158/1078-0432.CCR-15-2452 Prior presentation: Presented in part at the 2014 American Society of Clinical Oncology Annual Meeting, May 30–June 3, 2014, Chicago, IL (Abstract #520). ClinicalTrials.gov: NCT01381874 |
| Subjects: | Oncology |
| Divisions: | Departments > Department of Oncology and Medical Radiology |
| Depositing User: | Елена Шрамко |
| Date Deposited: | 14 Sep 2017 13:05 |
| Last Modified: | 14 Sep 2017 13:05 |
| URI: | http://repo.dma.dp.ua/id/eprint/1943 |
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