Preoperative Ca15-3 As a Predictor of Axillary Lymph Node Metastasis and Prognosis in Women With Breast Cancer: A Grade-Assessed Systematic Review and Meta-Analysis Publisher

Summary: Can a blood marker signal breast cancer outcomes? A pooled analysis linked higher CA15-3 with poorer survival and lymph-node spread; validation is needed. #BreastCancer #Biomarkers

Bahardoust M ; Rezaei A ; Hosseinali A ; Ranjbarpazuki G ; Salehi S ; Haghmoradi M ; Rahmati S ; Nafissi N
Source: Breast Cancer Published:2026

Abstract

Background: Breast cancer (BC) is the leading cause of cancer-related death among women. Axillary lymph node metastasis (ALNM) is a key prognostic factor, yet its assessment relies on invasive procedures. The prognostic value of preoperative CA15-3 remains controversial. We aimed to evaluate the association between preoperative CA15-3 levels and overall survival (OS), disease-free survival (DFS), and ALNM in breast cancer patients. Methods: We systematically searched PubMed, Scopus, Web of Science, Embase, and Cochrane Library up to January 2026. Cohort studies assessing preoperative CA15-3 and OS, DFS, or ALNM were included. Pooled hazard ratios (HRs) for OS and DFS, as well as pooled odds ratios (ORs) with 95% confidence intervals (CIs) for metastasis outcomes (Any metastasis or ALNM), were calculated using random-effects models. Results: Thirty-one cohort studies comprising 178,047 patients were included. Elevated CA15-3 was significantly associated with worse OS (HR: 1.91; 95% CI: 1.67–2.15), poorer DFS (HR: 2.04; 95% CI: 1.78–2.31), and increased metastasis risk (OR: 2.73; 95% CI: 2.04–3.42). The strongest association was observed for ALNM (OR: 3.08; 95% CI: 2.09–4.08). Subgroup and meta-regression analyses confirmed consistent findings across regions and identified age, tumor stage, and CA15-3 cutoff as heterogeneity sources. Conclusions: Elevated preoperative CA15-3 is significantly associated with reduced survival and increased ALNM risk. This association remained significant after adjustment for tumor characteristics in most primary studies, suggesting CA15-3 may reflect more aggressive tumor biology. These findings support CA15-3’s potential as an adjunctive biomarker; however, prospective validation is warranted. © The Author(s), under exclusive licence to The Japanese Breast Cancer Society 2026.