Heterogeneous treatment response in metastatic breast cancer: discordance between FDG-PET and CT classification

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Abstract Background Heterogeneous treatment response, characterized by simultaneous regression of some lesions and progression of others within the same patient, is increasingly recognized in metastatic breast cancer (mBC) and may reflect biological heterogeneity. However, this response pattern is not captured by current response assessment frameworks. We aimed to determine the prevalence of heterogeneous treatment response on FDG-PET and mixed response on CT during mBC systemic therapy. Methods This retrospective study included 51 female patients with mBC, treated between November 2017 and November 2025, each undergoing ≥ 2 FDG-PET/CT scans. Response was assessed according to RECIST 1.1 (CT) and PERCIST (FDG-PET), with using study‑specific definitions for heterogeneous/mixed response informed by literature. Results Heterogeneous metabolic response was observed in 30% of all follow‑up FDG‑PET examinations (40/132). These examinations accounted for 60% (40/67) of the scans classified as progressive metabolic disease (PMD) according to PERCIST. Among CT-examinations, 65 of 141 (46%) follow-up examinations had measurable disease; none of these scans (0/65, 0%) fulfilled the mixed response criteria. Conclusion In this real-world cohort of mBC undergoing systemic therapy, FDG-PET identified heterogeneous treatment response in a substantial proportion of patients; however, under current PERCIST criteria, these cases were uniformly classified as PMD. In contrast, using RECIST-inspired criteria, CT did not classify any patient as mixed response. These findings suggest that existing frameworks may not fully capture intra-patient response heterogeneity. As heterogeneous response is not an established PERCIST response category, further work is needed to determine how such patterns should be defined and incorporated into future response assessment frameworks. Clinical trial number Not applicable.