Diagnostic performance of a combined TAP, TAM, CA125 and CA153 panel for stage I breast cancer in patients with unilateral nipple discharge

Minimally invasive biomarkers that complement imaging may improve risk stratification in patients presenting with unilateral nipple discharge. The present study evaluated the diagnostic performance of tumor‑abnormal protein (TAP), tumor‑associated material (TAM), carbohydrate antigen 125 (CA125) and cancer antigen 153 (CA153) for breast cancer, individually and in combination, with a particular emphasis on stage I disease. The present retrospective single‑center study included 104 untreated patients with breast cancer and unilateral nipple discharge, including 25 patients with stage I disease, and 99 healthy controls. TAP, TAM, CA125 and CA153 were measured using standardized laboratory assays. Group differences were assessed using parametric or non‑parametric statistical tests as appropriate. Receiver operating characteristic analyses were performed for individual biomarkers, whereas a multivariable logistic regression model was used for the combined panel. Optimal cut‑off values were determined by maximizing Youden's index. TAP and TAM levels were significantly higher across all breast cancer stages compared with healthy controls, whereas CA125 and CA153 showed weaker stage‑specific differences. For comparing all breast cancer cases with controls, the area under the curve (AUC) values for TAP, TAM, CA125, CA153 and the combined model were 0.919, 0.862, 0.648, 0.607 and 0.963, respectively. For distinguishing stage I breast cancer from controls, the corresponding AUC values were 0.923, 0.891, 0.552, 0.531 and 0.959. Furthermore, the combined model achieved 92.0% sensitivity and 93.9% specificity for stage I disease. TAP and TAM biomarkers provided stronger diagnostic discrimination than conventional tumor antigens, and their integration with CA125 and CA153 improved diagnostic identification of early‑stage breast cancer compared with single‑biomarker assays. As such, the combined panel may serve as an adjunctive risk‑stratification tool in symptomatic patients with breast cancer, although prospective validation against benign breast disease is required.