A tumor-associated autoantibody panel for early detection of breast cancer in Sana’a, Yemen

Background: Breast cancer remains a major global health challenge and is the leading cause of cancer-related mortality among women worldwide. Early and accurate diagnosis is crucial for effective management. Tumor-associated autoantibodies may arise early during tumorigenesis and represent potential biomarkers for early cancer detection. This study aimed to evaluate a panel of tumor-associated autoantibodies for the early detection of breast cancer in Sana'a, Yemen. Methods: This diagnostic case-control study included 45 patients with newly diagnosed early-stage breast cancer and 45 healthy subjects in Sana'a city. Serum IgG autoantibodies against p53, MUC1, HER2, Cyclin B1, and c-Myc were measured using enzyme-linked immunosorbent assay (ELISA). An optimal diagnostic panel was constructed using forward stepwise logistic regression. The diagnostic performance of individual autoantibodies and the autoantibody panel was assessed using receiver operating characteristic (ROC) curve analysis. Key diagnostic indices, including sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR), were calculated. Results: Patients with early-stage breast cancer exhibited significantly higher serum levels of tumor-associated autoantibodies than healthy subjects (p < 0.01). The positivity frequencies of individual tumor-associated autoantibodies in breast cancer patients ranged from 26.7% to 40.0%. An optimized panel composed of tumor-associated autoantibodies against p53, HER2, Cyclin B1, and c-Myc demonstrated a marked increase in diagnostic sensitivity to 68.9% at a specificity of 93.3%, with an area under the ROC curve (AUC) of 0.898 (95% CI, 0.832–0.963). The panel showed a PPV of 91.2% and an NPV of 75.0%, with PLR and NLR values of 10.3 and 0.33, respectively. No significant correlation was observed between the levels of tumor-associated autoantibodies and breast cancer size, grade, or stage. Conclusions: The panel of tumor-associated autoantibodies targeting p53, HER2, Cyclin B1, and c-Myc shows potential for detecting early-stage breast cancer and could serve as a complementary tool to mammography, particularly in younger women and those with dense breast tissue, where imaging sensitivity is reduced. Further large-scale, multicenter validation studies are needed before clinical implementation.