HALP-H Index as a Prognostic Biomarker for Predicting Pathological Complete Response in Early-Stage HER2-Positive Breast Cancer—A Multicenter Retrospective Cohort Study

<b>Objectives:</b> Inflammation plays an important role in cancer development, and various inflammation parameters are used as potential prognostic markers. This study aimed to evaluate the effectiveness of the combined use of HALP and H index in predicting pathological response to neoadjuvant therapy in patients with HER2-positive early-stage breast cancer. <b>Method:</b> This retrospective cohort study was conducted on 146 HER2-positive breast cancer patients treated in two centers. To stratify patients by their predicted probability of pathological response, HALP and H index values were combined into a composite biomarker score called the combined response score (CRS). Patients were classified into three groups based on biomarker levels: 0 = low CRS (low predictive score), 1 = intermediate CRS, and 2 = high CRS (high predictive score). These groups reflect predicted response likelihood and do not represent actual pathological outcomes. Pathological response results were evaluated according to the combined response score. Pathological complete response (pCR) was defined as residual cancer burden (RCB) 0, indicating no residual invasive tumor in breast or lymph nodes. <b>Results:</b> The mean age of 146 early-stage breast cancer patients included in our study was 52.3 ± 11.3 (min: 29-max: 83). In the ROC analysis, the optimum cut-off value for the HALP score in pathological response classification was found to be 36 (AUC = 0.608, sensitivity = 76.29%, specificity = 44.9%, PPV = 73%, NPV = 47.89%) and 2.3 for the H index (AUC = 0.641, sensitivity = 65.98%, specificity = 51.02%, PPV = 72.73%, NPV = 43.1%). While the pathological complete response rate was 66.4% in all patients, it was 81.8% in those with a combined score of 2, 51% in those with a score of 1, and 58.6% in those with a score of 0 (<i>p</i> < 0.001). In the logistic regression analysis, the probability of pathological response in patients in the combined score = 2 group is 3.77 times higher than in group 0. In the Fagan nomogram, the pretest probability of pathological response is 66%, while the post-test probability for combined response score group 2 is 81.5%, and for the low-H index < 2.3 and the high-HALP ≥ 36 patient group, our estimate for pathological complete response increases to 82%. <b>Conclusions:</b> The HALP-H index combined score is an important predictor of pathological response in early-stage HER2-positive breast cancer patients, independent of histological type and stage. This new score may enable personalized approaches in treatment planning.