Subtype-Specific Metabolic Patterns in Staging Breast Cancer: Insights from Conventional and Parametric PET Radiomics

Background: Breast cancer (BC) is a biologically heterogeneous disease, with molecular subtypes differing fundamentally in terms of aggressiveness, metabolic behavior, and therapeutic response. Conventional ¹⁸F-FDG PET provides semi-quantitative assessment of glucose-analogue uptake using the standardized uptake value (SUV), whereas dynamic PET with Patlak analysis can estimate kinetic parameters such as the net influx rate constant (K_i) and the volume of distribution (V_d). However, the interpretation of these parameters in breast tissue remains insufficiently defined, and data across BC subtypes are limited. This proof-of-concept study explored the feasibility of deriving preliminary reference ranges for non-pathological breast tissue and describing subtype-specific patterns of kinetic parameters. Methods: Six breast cancer patients affected by Luminal (n = 4) or triple negative BC (TNBC, n = 3) and six control patients underwent dynamic ¹⁸F-FDG PET/CT. Patlak kinetic analysis generated parametric K_i and V_d maps. Lesion-level first-order radiomics features were extracted for each breast lesion. Non-lesional breast volumes (contralateral breast and breast excluding disease) were characterized to derive exploratory physiological reference ranges. Results: In control whole-breast tissue, median values were SUV 0.28 g/mL, K_i 0.056 mL/min/100 mL, and V_d ~9%. Non-lesional breast tissue in BC remained statistically concordant with controls. Lesion analysis suggested a possible metabolic gradient across subtypes: Luminal B with low proliferation activity exhibited lowest K_i (0.34 mL/min/100 mL), and highest V_d (~39%); Luminal A showed intermediate K_i (1.93 mL/min/100 mL) and V_d (~27%) values; TNBC showed higher K_i (3.02 mL/min/100 mL) with a greater proportion of zero-valued V_d voxels. Conclusions: This exploratory study suggests that parametric maps may be feasible for describing physiological breast tissue kinetic ranges and for exploring subtype-associated metabolic differences in BC. The observed K_i and V_d patterns may reflect differences in glucose phosphorylation and tracer distribution across tumor phenotypes, but the biological meaning of Patlak-derived parameters requires further methodological and histopathological validation. Larger prospective studies are needed before these parameters can be considered clinically applicable imaging biomarkers.