Evaluation of tumour heterogeneity by 18F-fluoroestradiol PET as a predictive measure in breast cancer patients receiving palbociclib combined with endocrine treatment
Cheng Liu, Shihui Hu, Xiaoping Xu, Yongping Zhang, Biyun Wang, Shaoli Song, Zhongyi Yang
Abstract
Abstract 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- 18 F-fluoro-17β-oestradiol ( 18 F-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 18 F-FES-PET/CT before the initiation of palbociclib. 18 F-FES uptake was quantified and expressed as the standardized uptake value (SUV). Interlesional heterogeneity was qualitatively identified according to the presence or absence of 18 F-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 18 F-FES-positive, 38 lesions were distributed across 10 patients without 18 F-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 18 F-FES-negative site developed PD, and the median PFS was only 2.4 months. Among 46 patients with only 18 F-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 18 F-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 18 F-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).