Clinical utility of molecular imaging in newly diagnosed metastatic breast cancer

Background: Optimizing patient outcome prediction in metastatic breast cancer (MBC) can potentially reduce patients’ and healthcare burden. Molecular imaging to visualize early metabolic change, baseline whole-body human epidermal growth factor receptor-2 (HER2) and estrogen receptor (ER) expression might achieve this. In the prospective multicenter IMPACT study, we evaluated the clinical utility of molecular imaging to improve standard diagnostics in patients with newly diagnosed MBC of all subtypes. Methods: Patients underwent extensive workup, including baseline metastasis biopsy, [¹⁸F]FDG-PET, [⁸⁹Zr]trastuzumab-PET (HER2-PET), [¹⁸F]FES-PET, and early [¹⁸F]FDG-PET after 2 weeks. Treatment was based on HER2 or ER subtype determined in biopsy (immunohistochemistry, IHC; standard-of-care) or PET findings (HER2- and [¹⁸F]FES-PET; investigational) in case of negative biopsy but positive HER2 and/or [¹⁸F]FES-PET scan. Clinical utility of molecular imaging was defined as the capacity to identify poor patient outcome, measured as progressive disease (PD) on CT at 8 weeks, progression-free survival (PFS), and overall survival (OS). Results: Two hundred patients were included. Progression on early [¹⁸F]FDG-PET was related to poor outcome in all subtypes (median PFS 4.1 versus 19.4 months, OS 19.4 versus 45.0 months). Early [¹⁸F]FDG-PET correctly predicted non-PD on 8 week CT (specificity 90.5%, negative predictive value 94.1%), but sensitivity and positive predictive value for PD was low (50 and 37.5%, respectively). However, early [¹⁸F]FDG-PET related better to long-term outcome than CT: patients with non-PD on 8 week CT, but with progression on early [¹⁸F]FDG-PET, had a median PFS and OS of 9.5 and 22.3 months respectively, compared to 19.4 and 50.1 months without [¹⁸F]FDG-PET progression (PFS HR 1.76 (95%CI 1.0 – 2.9), OS HR 1.93 (1.0 – 3.5)). HER2 or ER subtype was discrepant between biopsy and PET in 52 out of 200 (26%) patients, yielding investigational PET-based treatment options in 41 (21%) patients. In patients with HER2-positive biopsy IHC disease who received standard HER2-targeting treatment, median PFS with positive- versus negative HER2-PET was 23.2 and 4.5 months, respectively. In patients with biopsy IHC HER2-negative disease but positive HER2-PET, median PFS was with investigational HER2-targeted treatment 11.4 months, without 7.4 months. The pattern was similar in ER-positive disease, although less pronounced for biopsy- and PET-based subtypes. Conclusions: This study supports the clinical utility of molecular imaging with [¹⁸F]FDG-PET, HER2-PET, and [¹⁸F] FES-PET, to improve standard diagnostics for outcome and subtype assessment in patients with newly diagnosed MBC. Clinical trial information: NCT01957332. Research Sponsor: the Dutch Cancer Society; IMPACT (RUG 2012–5565).