Preoperative systemic inflammation response index: Clinicopathologic predictor of pathological complete response in HER2-positive breast cancer patients receiving neoadjuvant systemic therapy

Background: Multiple pretreatment systemic inflammatory markers (SIMs) have been reported as predictors of pathological complete response (pCR) after neoadjuvant systemic therapy (NST) in patients with breast cancer (BC). However, the most significant SIM remains to be conclusively identified, and variations among different molecular subtypes remain unknown. The objective of the study was to identify the most significant SIM in patients with human epidermal growth factor receptor 2 (HER2) positive BC, to construct a pCR-predictive nomogram combining it with other clinicopathologic factors, and to evaluate its prognostic value on survival. Methods: We retrospectively reviewed the findings for 240 patients with stage I-III HER2-positive BC who underwent NST and subsequent surgery at Kaohsiung and Taichung Veterans General Hospital from 2011 to 2021. Clinicopathologic factors were analyzed by stepwise logistic regression with backward selection. The data were used to construct a nomogram plot for determining the pCR probability. Kaplan-Meier curves and log-rank test were used to evaluate disease-free survival (DFS) and overall survival (OS). Results: Among the pretreatment SIMs, only the systemic inflammation response index (SIRI) was significantly related to pCR, with an optimal cutoff value of 1.27 x 10(9)/L. Stepwise logistic analyses indicated that clinical N stage, HER2 immunohistochemistry score, hormone receptor status, targeted therapy regimen, and SIRI were independent predictors of pCR, with an area under the curve of 0.722. The Hosmer-Lemeshow test and calibration curve revealed that the predictive ability was a good fit to actual observations. A nomogram was constructed based on the logistic model. The external validation of the model also revealed satisfactory discrimination and calibration. Kaplan-Meier analysis showed that patients with SIRI <1.27 had longer DFS and OS. Conclusion: Pretreatment SIRI <1.27 is predictive of pCR, DFS, and OS in HER2-positive BC. Our nomogram could efficiently predict pCR and facilitate clinical decision-making before neoadjuvant treatment.