Intrapatient 16a-[¹⁸F]Fluoro-17b-Estradiol PET Heterogeneity as a Prognostic Factor for Endocrine Therapy Response and Survival in Patients with Estrogen Receptor–Positive Metastatic Breast Cancer

Intrapatient heterogeneity of estrogen receptor (ER) expression on 16a-[¹⁸F]fluoro-17b-estradiol ([¹⁸F]FES) PET is related to outcome in patients with ER-positive metastatic breast cancer (MBC), but a validated and practical method to support clinical decision-making is lacking. Therefore, the [¹⁸F]FES PET heterogeneity score (i.e., percentage of [¹⁸F]FES-positive metastases) was validated as a prognostic factor for endocrine therapy response and survival in a large cohort of patients with newly diagnosed MBC. Furthermore, we explored 2 less laborious methods to predict the [¹⁸F]FES PET heterogeneity score. Methods: Patients with ER-positive MBC included in the IMPACT-MBC study, who received baseline [¹⁸F]FES and [¹⁸F]FDG PET and first-line endocrine therapy, were included in this subanalysis. ER homogeneous (100% [¹⁸F]FES-positive lesions) and ER heterogeneous (both [¹⁸F]FES-positive and [¹⁸F]FES-negative lesions) MBC was distinguished by manual segmentation of all lesions on [¹⁸F]FES PET and related to progression-free survival (PFS) and overall survival (OS). In addition, the positive predictive value of the visual assessment and the 5-largest-lesions assessment to predict homogeneous MBC in all lesions on [¹⁸F]FES PET was determined. Results: From the 102 MBC patients eligible for the present retrospective subanalysis, 46 had ER homogeneous MBC and 56 had ER heterogeneous MBC. Differences were found between ER homogeneous and ER heterogeneous MBC for median PFS (19.8 vs. 15.0 mo; hazard ratio, 0.63; 95% CI, 0.41–0.96; P 5 0.03) and median OS (62.5 vs. 34.7 mo; hazard ratio, 0.65; 95% CI, 0.38–1.08; P 5 0.09). Twenty-one (38%) of 61 patients with ER homogeneous MBC by visual analysis and 37 (45%) of 83 patients with ER homogeneous MBC by the 5-largest-lesions method had ER heterogeneous MBC by manual segmentation of all lesions on [¹⁸F]FES PET (positive predictive value, 0.66 and 0.55, respectively). Conclusion: Patients with ER-positive homogeneous MBC showed a trend toward superior PFS and OS compared with patients with ER heterogeneous MBC. This analysis confirmed and validated the prognostic value of the [¹⁸F]FES PET heterogeneity score for endocrine therapy response and survival in a large cohort of MBC patients. The less laborious visual and 5-largest-lesions methods were inferior compared with assessment based on the [¹⁸F]FES PET heterogeneity score in all lesions.