Abstract 803: Visualizing bicalutamide effect on androgen receptor availability in patients with metastatic breast cancer
Authors: Jorianne Boers, Clasina M. Venema, Erik FJ de Vries, Geke AP Hospers, Hendrikus H. Boersma, Bart Rikhof, Christine Dorbritz, Andor WJM Glaudemans, Carolina P. Schröder
Journal: Cancer Research (2020)

Abstract BACKGROUND: The androgen receptor (AR) is a potential new therapeutic target in metastatic breast cancer, but it is likely that only patients with tumors overexpressing AR can benefit. To non-invasively assess AR expression in all metastatic lesions, whole-body imaging techniques such as 16β-18F-fluoro-5α-dihydrotestosterone positron emission tomography (18F-FDHT-PET), can be used. 18F-FDHT uptake reduction during treatment with an AR antagonist may indicate effective targeting of AR, and therefore might be predictive for response to treatment. This study assessed the feasibility of 18F-FDHT-PET to detect changes in 18F-FDHT uptake during treatment with AR antagonist bicalutamide, and evaluated whether these changes were related to bicalutamide response. PATIENTS AND METHODS: Postmenopausal women with AR positive (&amp;gt;10% staining on primary tumor or metastasis biopsy), human epidermal growth factor receptor 2-negative metastatic breast cancer, regardless of estrogen receptor status, were eligible. At baseline, patients underwent a bone scintigraphy, and contrast-enhanced computed tomography, as part of standard staging. Metastatic lesions were identified on both imaging modalities. All patients received an 18F-FDHT-PET at baseline and after 4 to 6 weeks bicalutamide 150mg daily. Baseline 18F-FDHT uptake was expressed as maximum standardized uptake value (SUVmax). Change between baseline and repeated 18F-FDHT uptake was assessed as (difference of) SUVmax corrected for physiological background activity (SUVcor and ΔSUVcor), per patient and per lesion. Response evaluation was performed by radiological imaging according to RECIST 1.1 and/or clinical assessment. Clinical benefit was defined as absence of disease progression for at least 24 weeks. RESULTS: Twenty-one patients (mean age 65 years) with in total 536 metastatic lesions were included. Baseline 18F-FDHT-PET detected 341 of 515 lesions found with standard imaging, and 21 new lesions. Baseline 18F-FDHT uptake varied widely between patients (median SUVmax 2.62; range 1.58 - 5.58) and lesions (3.07; 0.64 - 20.24). Repeated 18F-FDHT-PET was evaluable in 17 patients with 349 metastatic lesions. Repeated 18F-FDHT uptake showed median SUVcor decrease from 1.30 to 0.72 per patient, and 1.26 to 0.69 per lesion (P &amp;lt; 0.001). Median ΔSUVcor per patient was −45% (range −72% to −7%), and per lesion −39% (−95% to +100%). In patients with clinical benefit on bicalutamide (n = 3), median ΔSUVcor was −49% versus −39% in patients without benefit (n = 14; P = 0.801). CONCLUSION: In this feasibility study, bicalutamide induced 18F-FDHT uptake change could be detected by repeated 18F-FDHT-PET in patients with AR positive metastatic breast cancer. However, in this small study, this change was not significantly related to bicalutamide response per patient. (NCT02697032) Funding by UMCG Healthy Ageing Pilots and de Cock-Hadders Foundation Citation Format: Jorianne Boers, Clasina M. Venema, Erik FJ de Vries, Geke AP Hospers, Hendrikus H. Boersma, Bart Rikhof, Christine Dorbritz, Andor WJM Glaudemans, Carolina P. Schröder. Visualizing bicalutamide effect on androgen receptor availability in patients with metastatic breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 803.