A Randomized Feasibility Study of ¹⁸F-Fluoroestradiol PET to Predict Pathologic Response to Neoadjuvant Therapy in Estrogen Receptor-Rich Postmenopausal Breast Cancer

The aim of this study was to explore the ability of ¹⁸F-fluoroestradiol (¹⁸F-FES) PET/CT imaging to predict pathologic response to neoadjuvant therapy in postmenopausal women with estrogen receptor (ER)-rich breast cancer. Methods: This was a prospective, single-center study conducted as a substudy of the neoadjuvant study of chemotherapy versus endocrine therapy in postmenopausal patients with primary breast cancer (NEOCENT) trial. Patients with ER-rich breast cancer were randomized to neoadjuvant chemotherapy (NC) or neoadjuvant endocrine therapy (NET). The baseline SUV_max of ¹⁸F-FES PET/CT was measured. The pathologic response was assessed by the Miller-Payne system as nonresponse (grades 1 and 2) and response (grades 3-5). Results: Twenty-six patients were enrolled, with pathologic response achieved in 25 (NC, 12; NET, 13). Two patients achieved pathologic complete response after NC, but the remaining 23 patients had residual disease after NC or NET. Eight of 12 patients responded to NC, and 4 of 13 to NET; the difference was marginally significant (P = 0.07). In the NC group, the 2 patients with ¹⁸F-FES-negative tumors and none of the 10 patients with ¹⁸F-FES-avid tumors achieved pathologic complete response (P = 0.02). No difference in the SUV_max between responders and nonresponders was observed in either group. However, 5 of 7 NC patients with a baseline SUV_max of less than 7.3 achieved pathologic response, whereas none of the 5 NET patients with an SUV_max of less than 7.3 were responders (P = 0.03). The SUV_max values of the NC group were negatively correlated with percentage reduction of tumor cellularity (r = -0.63, P = 0.03), whereas those of the NET group showed positive correlation (r = 0.62, P = 0.02). During the median follow-up of 74 mo (range, 44-85 mo), recurrence occurred in only 4 NET patients. In patients with an SUV_max of less than 7.3, recurrence occurred in none of the 8 NC patients and 2 of the 5 NET patients (P = 0.13). Conclusion: Postmenopausal women who are ER-positive, but ¹⁸F-FES-negative, may benefit from NC rather than NET. ¹⁸F-FES PET/CT has the potential to predict response to neoadjuvant therapy in postmenopausal women with ER-rich breast cancer.