Reconsidering the Value of Baseline PET/CT in Early-Stage Breast Cancer: Evidence for Selective Use from the MF21-02 Multicenter Study

Background: The role of ^18F-FDG PET/CT in the initial staging of early-stage breast cancer remains controversial, as current guidelines discourage its routine use due to the low prevalence of distant metastases. This study aimed to evaluate the diagnostic yield and clinical impact of baseline PET/CT in a large multicenter cohort. Methods: In this retrospective multicenter study, 997 patients with clinical stage I–II breast cancer who underwent baseline PET/CT prior to treatment planning were included. The primary outcome was the detection of distant metastases, and the secondary outcome was the impact of PET/CT findings on treatment decisions. Clinicopathological factors associated with PET/CT positivity were also analyzed. Results: PET/CT identified abnormal findings in 29 patients (2.9%), including distant metastases in 21 patients (2.1%). Treatment strategy was altered in 21 patients (2.1%), primarily due to upstaging to metastatic disease. PET/CT positivity increased with tumor stage (0.4% in stage I vs. 3.7% in stage IIB, p < 0.001). In multivariable analysis, HER2 positivity, clinical nodal positivity (cN1), and higher tumor stage (cT2–3 vs cT1) were independently associated with PET/CT positivity. Conclusion: In this real-world PET/CT-referred cohort of patients with clinically stage I–II breast cancer, clinically relevant additional findings were identified in only 2.9% of patients, indicating a low overall diagnostic yield. These findings support current recommendations against routine systemic FDG PET/CT staging in clinically early-stage disease. When PET/CT is contemplated, higher-risk clinical and biological features may support selective, patient-specific use rather than routine application.