Chemotherapy Shows a Better Efficacy Than Endocrine Therapy in Metastatic Breast Cancer Patients with a Heterogeneous Estrogen Receptor Expression Assessed by (18)F-FES PET

SIMPLE SUMMARY: About 10–20% of breast cancer patients have a heterogeneous estrogen receptor expression. The diagnosis and treatment strategy remains controversial in these patients, especially regarding the metastatic pattern. The aim of our study was to investigate the occurrence and properties of estrogen receptor heterogeneity and to evaluate the following treatment efficacy among a certain group of metastatic breast cancer patients. We found the novel (18)F-FES PET/CT method could identify patients with estrogen receptor heterogeneity, and chemotherapy showed a better efficacy compared with endocrine therapy in these patients. Our findings could give valuable suggestions to physicians and researchers in clinical practice. ABSTRACT: Background: The heterogeneity of estrogen receptor (ER) expression has long been a challenge for the diagnosis and treatment strategy of metastatic breast cancer (MBC). A novel convenient method of ER detection using (18)F-fluoroestradiol positron emission tomography/computed tomography ((18)F-FES PET/CT) offers a chance to screen and analyze MBC patients with ER uncertainty. Methods: MBC patients who received (18)F-FES PET/CT were screened and patients with both FES positive (FES+) and negative (FES-) lesions were enrolled in this study. Progression-free survival (PFS) was estimated using the Kaplan–Meier method and was compared using the log-rank test. Results: A total of 635 patients were screened and 75 of 635 (11.8%) patients showed ER uncertainty; 51 patients received further treatment and were enrolled in this study. Among them, 20 (39.2%) patients received chemotherapy (CT), 21 (41.2%) patients received endocrine-based therapy (ET), and 10 (19.6%) patients received combined therapy (CT + ET). CT showed a better progression-free survival (PFS) compared with ET (mPFS 7.1 vs. 4.6 months, HR 0.44, 95% CI 0.20–0.93, p = 0.03). CT + ET did not improve PFS compared with either CT or ET alone (mPFS 4.4 months, p > 0.2). All three treatment options were well tolerated. Conclusions: (18)F-FES PET/CT could identify patients with ER heterogeneity. Patients with bone metastasis are more likely to have ER heterogeneity. Patients with ER heterogeneity showed better sensitivity to CT rather than ET. Combined therapy of CT + ET did not improve the treatment outcome.