Comparative analysis of metabolic characteristics and prognostic stratification of HER2-low and HER2-zero breast cancer using ¹⁸F-FDG PET/CT imaging

Background: Recent advancements in novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) have highlighted the emerging HER2-low breast cancer subtype with promising therapeutic efficacy. This study aimed to comparatively analyze the metabolic characteristics and prognostic stratification of HER2-low and HER2-zero breast cancer using baseline fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) imaging.

Methods: Consecutive patients with newly diagnosed breast cancer who underwent ¹⁸F-FDG PET/CT prior to therapy in our hospital were retrospectively reviewed. The relationship between metabolic parameters (maximum standardized uptake value (SUVmax), tumor-to-liver SUV ratio (TLR), total lesion glycolysis (TLG), and metabolic tumor volume (MTV)) in primary lesions and HER2 expression was analyzed. The survival analyses were performed to identify the prognostic factors for disease-free survival (DFS) in patients with HER2-negative (HER2-low versus -zero).

Results: In total, 258 patients (mean age: 54 ± 12 years) were included. In hormone receptor (HR)-positive subgroup, SUVmax and TLR were significantly higher in HER2-low than in HER2-zero (P = 0.045 and 0.03, respectively). But in HR-negative subgroup, there was no significant metabolic difference between HER2-low and HER2-zero (All P > 0.05). The four metabolic parameters were significant predictors of DFS in HER2-negative patients (All P < 0.01), but there was no significant difference in DFS between HER2-low and -zero, regardless of tumor metabolism. Moreover, in HER2-zero patients, the DFS of patients with high metabolism was significantly shorter than that of patients with low metabolism (P_SUVmax = 0.002, P_MTV = 0.03, P_TLG= 0.005, P_TLR < 0.001, respectively), but without a similar finding in HER2-low patients.

Conclusion: Our study demonstrated the HR-positive HER2-low breast cancer exhibited a particularity in glucose metabolic profile. Additionally, HER2-zero patients with elevated metabolism were associated with inferior prognosis and warranted careful attention in clinical evaluations.