Prognostic value of baseline FDG PET/CT in HER2-positive metastatic breast cancer treated with first-line trastuzumab, pertuzumab, and docetaxel

Background: Trastuzumab, pertuzumab, and docetaxel (THP) have represented the standard first-line treatment for HER2-positive metastatic breast cancer (MBC) for over a decade, following the pivotal CLEOPATRA trial. However, interim results from the DESTINY-Breast09 trial suggest that trastuzumab deruxtecan (T-DXd) may soon replace THP as the new first-line standard. Recent developments in treatment have raised new questions about how best to match therapy intensity with individual patient profiles. FDG PET/CT, routinely used for metabolic imaging, might help by identifying patients with differing prognoses based on baseline tumor activity. We investigated the prognostic relevance of baseline FDG PET/CT and its association with treatment outcomes in HER2-positive MBC patients receiving first-line THP. Methods: We retrospectively analyzed 194 patients with HER2-positive MBC who underwent baseline FDG PET/CT within 12 months before initiating THP therapy (2017–2024). SUVmax was recorded, and optimal cut-off values for progression-free survival (PFS) was determined by ROC analysis. Cox regression and logistic regression were used to identify independent predictors of PFS, OS, and long-term response (PFS ≥ 35 months). Results: Median PFS was 29.1 months; 2-year PFS was 60.3%. SUVmax > 9.6 was associated with significantly shorter PFS (18.9 vs. 43.9 months; p = 0.002) and remained independently prognostic in multivariate analysis (HR 1.98; p = 0.001). Median OS was 85.0 months. Among 162 evaluable patients, 35% were classified as long responders. ER positivity (OR 4.82), oligometastatic disease (OR 2.60), and low SUVmax (≤ 9.6; OR 2.78) were independent predictors of durable benefit. Conclusions: Baseline SUVmax derived from FDG PET/CT is an independent predictor of PFS in HER2-positive MBC treated with first-line THP. Integration of metabolic imaging biomarkers with clinical and molecular factors may support more personalized treatment approaches in this evolving therapeutic setting.