Preoperative CALLY Index and Postoperative Pathological Axillary Nodal Status in Breast Cancer: Association with Nodal Metastasis and Exploratory Analysis of Observed Pathological Nodal Burden

Background/Objectives: The C-reactive protein–albumin–lymphocyte (CALLY) index integrates systemic inflammation, nutritional status, and host immunity. We evaluated its association with postoperative pathological axillary nodal status and its incremental discrimination beyond routinely recorded preoperative clinical factors. Methods: This retrospective single-center diagnostic-accuracy study screened 380 patients evaluated between July 2019 and January 2026. The primary cohort included 247 unilateral M0 patients undergoing upfront surgery; 80 neoadjuvant-treated M0 patients were analyzed separately. CALLY was calculated from laboratory values obtained within 7 days before surgery. Associations and discrimination were assessed using logistic regression, Firth penalized logistic regression when clinical nodal status caused separation, paired bootstrap AUC comparisons, restricted cubic splines, and prespecified sensitivity analyses for BMI and available inflammatory/comorbidity covariates. Results: In the primary cohort, 75 patients (30.4%) were pN-positive. Median CALLY was 2.629 in pN-positive and 3.586 in pN0 patients (p = 0.058), and standalone discrimination was weak (AUC = 0.576; 95% CI, 0.496–0.651). In the age- and cT-adjusted model, the OR per CALLY doubling was 0.89 (95% CI, 0.72–1.10; p = 0.271). Preoperative cN status nearly separated the outcome; in a Firth model including age, cT, cN, and CALLY, the CALLY OR was 0.78 (profile 95% CI, 0.51–1.21; p = 0.250). Adding CALLY to age, cT, and cN changed the AUC from 0.988 to 0.988 (ΔAUC = −0.0001; 95% CI, −0.0013 to 0.0041; p = 0.551). No nonlinearity was detected (p = 0.352), and BMI/confounder sensitivities were concordant. Secondary neoadjuvant and observed-burden analyses remained exploratory and imprecise. Conclusions: In this single-center upfront-surgery cohort, preoperative CALLY was not independently associated with postoperative axillary nodal positivity and provided no convincing incremental discrimination beyond the available clinical assessment. The data do not support using CALLY alone for axillary staging or surgical decisions; limited high-burden event counts preclude a definitive exclusion of smaller associations.