Impact of Neoadjuvant Chemotherapy on Hormone Receptor Status and Systemic Inflammatory Markers in Breast Cancer Patients: A Retrospective Cohort Study

Introduction: Breast Cancer (BC) remains the leading cause of cancer-related morbidity and mortality among women worldwide. Neoadjuvant Chemotherapy (NACT) is important in treating both locally advanced and early-stage BCs, as it helps make breast-conserving surgery possible and improves patient outcomes. However, not all patients respond to NACT equally. Finding reliable prognostic markers after NACT is essential for selecting optimal follow-up treatments and improving patient outcomes. Systemic inflammatory markers derived from peripheral blood, including abnormal blood counts, the Neutrophil-To-Lymphocyte Ratio (NLR), and the Platelets-toLymphocyte Ratio (PLR), have been widely investigated as surrogate indicators of host-tumour interaction in BCs. These should be contextualised with pre-treatment hormonal receptor status and tumour biology, when evaluating response to NACT. Aim: To determine whether changes in systemic inflammatory markers (NLR and PLR) and Hormone Receptor (HR) status during NACT are associated with pathological response by Miller-Payne scoring (MPS). Materials and Methods: This retrospective cohort study was conducted in the Department of Pathology, RL Jalappa Hospital, Kolar, Karnataka, India, from January 2023 to December 2024. It included data of 25 patients, collected retrospectively from the registers maintained in the department, who had pretreatment biopsy and post-NACT resection specimens, along with hormonal receptor status. Pathological response was assessed using the MPS scoring. Peripheral blood parameters like WBC, absolute neutrophils, lymphocytes count and platelets count were obtained, and NLR, and PLR were calculated using standard formulae. Paired t-test and Spearman’s correlation coefficient were used for statistical analysis. Results: A total of 25 BC patients treated with NACT were analysed. The median age at diagnosis was 51 years, with 12 patients (48%) aged ≤50 years and 13 patients (52%) aged >50 years. Pathological response assessed by MPS showed grade 3 as the most common response (40%), while major pathological response (grades 4-5) was observed in 20% of cases. Neutrophil proportion increased significantly after chemotherapy (p-value=0.024), whereas changes in total White Blood Cell (WBC) count, lymphocyte proportion and platelet count were not significant. A significant reduction in NLR category was observed after treatment (p-value=0.003), whereas PLR did not change significantly (p-value=0.06). Spearman correlation showed no significant correlation between NLR (ρ=0.25, p-value=0.23) or PLR (ρ=0.06, p-value=0.76) and pathological response. Although Receiver Operating Characteristic (ROC) yielded a high Area Under the Curve (AUC) values for NLR (AUC=1.00) and PLR (AUC=0.94) these results should be interpreted as exploratory due to small sample size and lack of external validation rather than definitive. HR status, Human Epidermal Growth Factor Receptor 2 (HER2) and Ki-67 did not show significant association with pathological response. Conclusion: Systemic inflammatory markers demonstrated post-treatment changes following NACT; nevertheless, NLR and PLR did not show a significant correlation or association with pathological response. Although ROC analysis indicated potential discriminatory value, inflammatory markers cannot be considered independent predictors of response.