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 18F-fluoroestradiol positron emission tomography/computed tomography (18F-FES PET/CT) offers a chance to screen and analyze MBC patients with ER uncertainty. Methods: MBC patients who received 18F-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: 18F-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.
Background
Predictive biomarkers are needed to identify oestrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer (MBC) patients who would likely benefit from cyclin-dependent kinase 4 and 6 inhibitors combined with endocrine therapy. Therefore, we performed an exploratory study to evaluate the tumour heterogeneity parameters based on 16α-18F-fluoro-17β-oestradiol (18F-FES)-PET imaging as a potential marker to predict progression-free survival (PFS) in MBC patients receiving palbociclib combined with endocrine therapy.
Methods
Fifty-six ER + MBC patients underwent 18F-FES-PET/CT before the initiation of palbociclib. 18F-FES uptake was quantified and expressed as the standardized uptake value (SUV). Interlesional heterogeneity was qualitatively identified according to the presence or absence of 18F-FES-negative lesions. Intralesional heterogeneity was measured by the SUV-based heterogeneity index (HI = SUVmax/SUVmean). Association with survival was evaluated using the Cox proportional hazards model.
Results
A total of 551 metastatic lesions were found in 56 patients: 507 lesions were identified as 18F-FES-positive, 38 lesions were distributed across 10 patients without 18F-FES uptake, and the remaining 6 were liver lesions. Forty-three patients obtained a clinical benefit, and 13 developed progressive disease (PD) within 24 weeks. Nine out of 10 patients with an 18F-FES-negative site developed PD, and the median PFS was only 2.4 months. Among 46 patients with only 18F-FES-positive lesions, only four patients had PD, and the median PFS was 23.6 months. There were statistically significant differences between the two groups (P < 0.001). For the subgroup of patients with only 18F-FES-positive lesions, low FES-HI patients experienced substantially longer PFS times than those with high FES-HI (26.5 months vs. 16.5 months, P = 0.004).
Conclusions
18F-FES-PET may provide a promising method for identifying and selecting candidate ER + /HER2- MBC patients who would most likely benefit from palbociclib combined with endocrine treatment and could serve as a predictive marker for treatment response.
Trial registration NCT04992156, Date of registration: August 5, 2021 (retrospectively registered).
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