Diagnostic Performance of ⁶⁸Ga-FAPI PET/CT, ¹⁸F-FDG PET/CT, and Breast MRI for Assessing Tumor Extent and Axillary Metastasis in Breast Cancer: A Histopathology-Referenced Retrospective Study.

PURPOSE: To compare the diagnostic performance of ⁶⁸Ga-FAPI PET/CT, ¹⁸F-FDG PET/CT, and magnetic resonance imaging (MRI) in assessing primary tumor size, detecting additional intramammary foci, and identifying axillary lymph node metastasis (ALNM) in patients with invasive breast cancer (IBC) undergoing upfront surgery without neoadjuvant chemotherapy (NAC), using postoperative histopathology as the reference standard.

METHODS: This retrospective study included 60 IBC patients who underwent total mastectomy without NAC. All patients had preoperative ⁶⁸Ga-FAPI PET/CT, ¹⁸F-FDG PET/CT, and breast MRI. Primary tumor size, multifocality/multicentricity (MF/MC), and ALNM were evaluated for each modality. FAPI and FDG were additionally assessed for extra-axillary lymph nodes, internal mammary nodes, and distant metastases. Agreement between imaging- and pathology-based tumor size measurements, as well as the diagnostic performance for MF/MC and ALNM, were evaluated using correlation analyses and standard diagnostic accuracy metrics.

RESULTS: MRI (ρ = 0.866) and ⁶⁸Ga-FAPI PET/CT (ρ = 0.844) demonstrated the strongest correlation with pathologic tumor size, whereas ¹⁸F-FDG PET/CT showed lower agreement (ρ = 0.780). Breast MRI (45.0%) and ⁶⁸Ga-FAPI-PET/CT (38.3%) were significantly superior to ¹⁸F-FDG PET/CT (18.3%) in detecting multifocal or multicentric disease (p < 0.001). For ALNM detection, breast MRI achieved the highest sensitivity (87.5%) but showed lower specificity (72.7%). In contrast, ⁶⁸Ga-FAPI PET/CT combined high sensitivity (81.2%) with perfect specificity (100.0%), outperforming ¹⁸F-FDG PET/CT, which demonstrated lower sensitivity (43.8%) despite high specificity (93.2%). Additionally, ⁶⁸Ga-FAPIPET/CT identified metastatic findings not detected by ¹⁸F-FDG PET/CT, including seven axillary lymph nodes (11.7%), 29 additional intramammary tumor foci (48.3%), and four distant metastases (6.7%).

CONCLUSION: ⁶⁸Ga-FAPI PET/CT demonstrated higher diagnostic performance than ¹⁸F-FDG PET/CT and accuracy comparable to breast MRI for primary tumor size estimation and detection of multifocal or multicentric disease. FAPI-PET/CT also provided higher specificity than MRI for ALNM assessment and identified additional metastatic lesions not detected by FDG-PET/CT, supporting its potential role as a complementary modality to MRI and an alternative functional imaging technique in selected patients.