Association of tumor markers CA 15-3, CEA, and CA 125 with [18F]NaF PET findings in breast cancer patients

Elevated CA 15-3 and CEA independently predict [¹⁸F]NaF PET positivity in breast cancer. Optimal cut-offs were 19.25 U/mL for CA 15-3 (sensitivity 70.1%, specificity 90.4%, LR + 7.38, AUC 0.837) and 3.15 ng/mL for CEA (sensitivity 65.6%, specificity 85.2%, LR + 4.43, AUC 0.821). The clinical utility of CA 15-3 and CEA lies in rule-in and risk-stratification strategies. Patients above these thresholds, particularly those with invasive lobular carcinoma undergoing restaging, may benefit from prioritized [¹⁸F]NaF PET evaluation or improved interpretation of equivocal PET findings. CA 15-3 threshold, lower than routine laboratory reference, may guide aggressive screening and prioritized [¹⁸F]NaF PET in patients with high clinical suspicion. Multivariable model combining CA 15-3, CEA, and CA 125 (probability cut-off 0.29) improved diagnostic performance (sensitivity 79.7%, specificity 92.3%, AUC 0.863). Integrating CA 15-3 and CEA into clinical decision-making may enable a nuanced, risk-adapted approach, optimizing metastasis detection and resource allocation.