The Schrödinger’s Cat Paradox: Can MAMMI PET with ⁶⁸ Ga-FAPI Determine Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Omitting Surgery?

<b><i>Aim:</i></b> This study aims to evaluate the utility of ⁶⁸Ga-FAPI PET/CT in combination with MAMMI PET for assessing pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) in patients with breast cancer. <b><i>Materials and Methods:</i></b> This study retrospectively reviewed patients with breast cancer who underwent NACT and had pre/post-therapy imaging with ¹⁸F-FDG PET/CT, ⁶⁸Ga-FAPI PET/CT, and ⁶⁸Ga-FAPI MAMMI PET. Radiological and histopathological findings before and after treatment were documented. Quantitative PET parameters were calculated, and the post-therapy diagnostic performance of PET imaging was assessed using ROC analysis. Threshold values for detecting residual tumor were calculated, and univariate and multivariate analyses were performed for the breast and axilla. <b><i>Results:</i></b> Twenty female patients were included. In visual assessment of residual tumor detection in the breast, the sensitivity, specificity, and accuracy were as follows: 73%, 70%, and 71% for ¹⁸F-FDG PET/CT; 73%, 80%, and 76% for ⁶⁸Ga-FAPI PET/CT; and 64%, 70%, and 67% for ⁶⁸Ga-FAPI MAMMI PET (all lesions); for detecting residual disease in the axilla, the metrics were: 33%, 91%, and 71% for ¹⁸F-FDG PET/CT; 50%, 100%, and 82% for ⁶⁸Ga-FAPI PET/CT; and 50%, 70%, and 63% for MRI. In quantitative analysis, post-therapy ⁶⁸Ga-FAPI MAMMI PET tumor background rate (TBR) SUV_max was the only significant parameter in multivariate analysis, demonstrating 91% sensitivity, 80% specificity, and 86% accuracy at a threshold value of 1.35 for detecting residual tumor (<i>p =</i> 0.002; AUC: 0.900; 95% CI: 0.765-1.000). <b><i>Conclusions:</i></b> The diagnostic performance of quantitative parameters derived from ⁶⁸Ga-FAPI PET/CT combined with MAMMI PET was superior to current diagnostic methods for determining pCR in the breast; however, the sensitivity in the axilla remains limited. Further research in larger patient groups should be conducted.