The Pan-Immune-Inflammation-Value Predicts the Survival of Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Breast Cancer Treated with First-Line Taxane-Trastuzumab-Pertuzumab

Simple Summary Although taxane-trastuzumab-pertuzumab combinations in the first-line treatment setting significantly improved clinical outcomes in patients with Human Epidermal growth factor Receptor 2 positive (HER2+) advanced breast cancer (aBC), their clinical efficacy is highly heterogeneous, and reliable biomarkers of benefit from this treatment are lacking. Different peripheral blood parameters have emerged as prognostic biomarkers in breast cancer, but their predictive role in HER2+ BC patients receiving dual anti-HER2 blockade remains unclear. In this work, we identified the Pan-Immune-Inflammatory Value (PIV), a recently defined parameter, taking into account peripheral blood neutrophil, platelet, monocyte and lymphocyte counts, as an independent predictor of worse OS in patients with HER2+ aBC receiving first line trastuzumab-pertuzumab biochemotherapy. The PIV outperforms other well-known peripheral blood parameters, thus potentially representing a new tool to improve the prognostic stratification of HER2+ aBC patients in a first-line treatment setting. Different peripheral blood parameters have emerged as prognostic biomarkers in breast cancer (BC), but their predictive role in Human Epidermal growth factor Receptor 2 positive (HER2+) advanced BC (aBC) patients receiving dual anti-HER2 blockade remains unclear. We evaluated the impact of the Pan-Immune-Inflammatory Value (PIV), defined as the product of peripheral blood neutrophil, platelet, and monocyte counts divided by lymphocyte counts, on the prognosis of HER2+ aBC patients treated with first line trastuzumab-pertuzumab-based biochemotherapy. We also evaluated the association between the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the monocyte to lymphocyte ratio (MLR) and clinical outcomes. Cox regression models were used to estimate the impact of these variables, as well as of other clinically relevant covariates, on patient survival. We included 57 HER2+ aBC patients treated with taxane-trastuzumab-pertuzumab in our Institution. High baseline MLR, PLR, and PIV were similarly predictive of worse PFS at univariate analysis, but only high PIV was associated with a trend toward worse PFS at multivariable analysis. Regarding OS, both high PIV and MLR were associated with significantly worse patient survival at univariate analysis, but only the PIV was statistically significantly associated with worse overall survival at multivariable analysis (HR 7.96; 95% CI: 2.18-29.09). Our study reveals the PIV as a new and potent predictor of OS in HER2+ aBC patients treated with first line trastuzumab-pertuzumab-containing biochemotherapy. Prospective studies are needed to validate this new prognostic parameter in HER2+ aBC.

Automated summary

The Pan-Immune-Inflammatory Value (PIV) in peripheral blood may serve as a new and powerful predictor of overall survival in HER2+ advanced breast cancer patients treated with first-line trastuzumab-pertuzumab-containing biochemotherapy, potentially improving prognostic stratification in this patient population.