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

Abstract

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.

Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy

“…PIV is a new blood-based biomarker integrating different peripheral blood immune cell subpopulations-neutrophil, platelet, monocyte, and lymphocyte. Due to its potential to represent comprehensively patient's immunity and systemic inflammation, PIV was proposed as a stronger predictor of outcomes in advanced cancer patients receiving cytotoxic chemotherapy, immunotherapy, and targeted therapy 18 , 37 – 39 . Recently, Ligorio reported that PIV was firmly associated with survival and outperformed NLR, PLR, and MLR in predicting survival in patients with HER-2 positive advanced breast cancer 39 .…”

“…Due to its potential to represent comprehensively patient's immunity and systemic inflammation, PIV was proposed as a stronger predictor of outcomes in advanced cancer patients receiving cytotoxic chemotherapy, immunotherapy, and targeted therapy 18 , 37 – 39 . Recently, Ligorio reported that PIV was firmly associated with survival and outperformed NLR, PLR, and MLR in predicting survival in patients with HER-2 positive advanced breast cancer 39 . In line with the studies mentioned above, we showed that patients with low PIV scores had better survival outcomes.…”

PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients

“…As a measurement of the number of mutations carried by tumor cells, TMB could be a candidate as a predictive factor of immunotherapy in genomic-instable cancers, including SCLC (18). Studies showed that SCLC patients with higher TMB were more likely to benefit from anti-PD-1 inhibitor (19,20). Another factor, ctDNA, was strongly associated with the prognosis of SCLC patients treated with second-line immunotherapy, but the technique [nextgeneration sequencing (NGS)] and expensive cost of TMB and ctDNA evaluations strongly restrict practical clinical applications (13)(14)(15).…”

“…Due to its potential ability to comprehensively reveal systemic immune and cancer-related inflammation status, PIV has been regarded as a reliable predictor of clinical outcomes in advanced cancer patients. Ligorio reported that PIV was an independent predictor of worse OS in patients with HER2-positive advanced breast cancer receiving first-line trastuzumab-pertuzumab biochemotherapy, and PIV outperformed other well-known peripheral blood parameters, such as NLR, PLR, and LMR (20). A pooled analysis also showed that PIV is a new prognostic biomarker in patients with metastatic colorectal cancer treated with first-line therapy and superior to other inflammatory indexes (14,15).…”

Post treatment NLR is a predictor of response to immune checkpoint inhibitor therapy in patients with esophageal squamous cell carcinoma

“…Therefore, it is urgent for us to find out effective biomarkers to estimate the efficacy of anti-PD-1/PD-L1 treatment in patients with ESCC. In previous study, peripheral blood parameters can reflect the system state of human bodies [ 15 – 17 ]. NLR and other hematologic parameters have become biomarkers to predict the overall survival (OS) and anti-PD-1 / PD-L1 treatment effect of diverse types of cancer [ 18 , 19 ].…”