Succinct summary of the response-adaptive breast cancer care in the grey zones.
| Topic | Core value | Main clinical use case | Key limitation | Take-home message |
|---|---|---|---|---|
| ER-targeted PET ([18F]FES PET/CT) | Whole-body functional ER mapping (captures heterogeneity and receptor discordance) | Suspected ER discordance, mixed endocrine response, biopsy not feasible | Physiologic/background uptake in some organs; not a substitute for histology in all casesEvidence status: supported by meta-analyses and growing clinical experience in selected ER-positive scenarios; not a universal replacement for biopsy. | Best used to answer a specific endocrine decision question (continue/switch endocrine strategy, target biopsy) |
| HER2-targeted PET | Whole-body HER2 expression assessment beyond a single biopsy | Suspected HER2 conversion/heterogeneity in metastatic disease, especially when tissue is inaccessible | Limited availability, logistics, tracer timing, and standardisationEvidence status: promising but mostly small, feasibility-based or specialised-centre evidence; clinical utility still requires validation. | Useful as a problem-solving biomarker to support anti-HER2 treatment selection or biopsy prioritisation |
| FDG PET/CT under immunotherapy | Whole-body tumour burden + early metabolic response + potential detection of immune-related adverse events | Response assessment during immune checkpoint inhibitor treatment; equivocal progression | Pseudoprogression/dissociated response can mislead early interpretationEvidence status: Biologically plausible and clinically useful in selected cases, but immunotherapy-specific criteria require TNBC-specific validation. | Interpret with immunotherapy-aware criteria and confirmation strategy |
| FDG PET/CT + ctDNA kinetics (combined approach) | Combines spatial lesion-level information (PET) with temporal systemic molecular dynamics (ctDNA) | Early escalation/de-escalation decisions, discordant response patterns, oligoprogression | Timing/threshold harmonisation, assay variability, and risk of overtestingEvidence status: conceptual and trial-ready; not yet validated for routine escalation/de-escalation. | Most powerful when embedded in a predefined action algorithm |
[18F]FES: 16α-[18F]fluoro-17β-estradiol; ctDNA: circulating tumour DNA; ER: oestrogen receptor; TNBC: triple-negative breast cancer; HER2: human epidermal growth factor receptor 2; PET/CT: positron emission tomography/computed tomography.