CALLY index as an independent predictor of pathological complete response in HER2-positive breast cancer receiving neoadjuvant therapy.

[PURPOSE] Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is a validated endpoint for long-term survival in HER2-positive breast cancer. Identifying clinical and biomarker-based predictors of pCR is essential for optimizing treatment strategies. This study investigated the predictive role of nutrition- and inflammation-based indices (HALP, CALLY, PNI, SII, PIV, SIRI, NLR) in determining pCR.

[METHODS] A total of 169 HER2-positive patients who underwent NACT followed by surgery at Ankara Etlik City Hospital between January 2023 and December 2024 were retrospectively analyzed. Indices were calculated from baseline laboratory values. Receiver operating characteristic (ROC) analysis was used to evaluate discriminatory ability and determine cut-off values for significant variables. Univariate logistic regression was performed initially; variables significant at the univariate level were included in the multivariate model.

[RESULTS] The overall pCR rate was 56.8%. ROC analysis identified the CALLY index (AUC = 0.681; p < 0.001) and Ki-67 (AUC = 0.603; p = 0.022) as significant predictors, while HALP, PNI, NLR, PIV, SII, and SIRI lacked predictive value. In univariate analysis, high CALLY (p < 0.001), high Ki-67 (p = 0.012), and pertuzumab-containing regimens [AC + taxane + trastuzumab + pertuzumab (p = 0.003) and docetaxel + trastuzumab + carboplatin + pertuzumab (THCP) (p = 0.004)] were associated with higher pCR, whereas ER positivity was associated with a reduced likelihood of pCR (OR = 0.41; p = 0.011). In multivariate analysis, CALLY (OR = 4.03; p < 0.001), Ki-67 (OR = 2.21; p = 0.038), and pertuzumab-containing regimens remained independent predictors: AC + taxane + trastuzumab + pertuzumab (OR = 3.24; p = 0.020) and THCP (OR = 3.86; p = 0.037). Although ER positivity was significant in univariate analysis, it lost statistical significance in the multivariate model (OR = 0.49; p = 0.072).

[CONCLUSIONS] High CALLY index and high Ki-67 were found to be statistically significant in predicting pCR, and pertuzumab-containing regimens were shown to increase pCR rates. In contrast, classical histopathological parameters and other immunonutritional scores demonstrated limited predictive value. These findings require validation through prospective, multicenter studies. The limited number of studies investigating the association between pCR and CALLY highlights the originality of our work.