Clinical and prognostic significance of the C-reactive protein-albumin-lymphocyte (CALLY) index in breast cancer: a systematic review and meta-analysis

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index integrates inflammatory, nutritional and immune-related biomarkers and may offer an accessible measure of host status in breast cancer. However, its prognostic relevance and clinical value remain uncertain. This systematic review and meta-analysis evaluated its associations with survival and treatment response and examined predictive performance. Methods: PubMed, Embase, Scopus and Web of Science were searched from inception to 1 October 2026, supplemented by reference-list and forward-citation searching. Studies evaluating CALLY in adults with invasive breast cancer were eligible. Multivariable-adjusted hazard ratios (HRs) comparing low versus high baseline CALLY were pooled using restricted maximum likelihood random-effects models with modified Hartung-Knapp intervals. Risk of bias and evidence certainty were assessed using the Newcastle-Ottawa Scale and GRADE, respectively. Results: Nine publications included 2,568 reported patients. Four studies comprising 1,394 patients contributed to each survival synthesis. Low CALLY yielded pooled HRs of 2.03 for overall survival (95% CI 1.20-3.45; I2=72.4%) and 2.00 for disease-free survival (95% CI 0.91-4.41; I2=77.7%). Both intervals included no association. In one HER2-positive cohort, low baseline CALLY was associated with lower odds of pathological complete response (adjusted OR 0.25, 95% CI 0.12-0.50). Apparent overall-survival area under the receiver-operating-characteristic curve (AUC) ranged from 0.688 to 0.740. External validation and demonstrated clinical utility were absent. Conclusions: CALLY shows potential prognostic and treatment-response associations, but imprecision, heterogeneity and limited validation prevent routine clinical adoption. Standardized measurement, prospective validation and demonstration of incremental clinical value are needed. Keywords: Breast cancer; C-reactive protein-albumin-lymphocyte index; Prognosis; Survival; Pathological complete response; Meta-analysis