# RBC balanced immuno-inflammatory signatures identify advanced breast cancer patients on CDK4/6 inhibitors at increased risk of progression and death

## TL;DR

This study shows that RBC-based immuno-inflammatory scores can better predict outcomes and side effects in breast cancer patients taking CDK4/6 inhibitors compared to traditional methods.

## Contribution

The RBC-IMM score and phosphatidylcholine-based model offer novel predictive tools for CDK4/6 inhibitor treatment outcomes in advanced breast cancer.

## Key findings

- RBC-IMM score accurately predicts progression-free survival and death in CDK4/6 inhibitor-treated patients.
- RBC-IMM outperforms classical immuno-inflammatory scores in predicting clinical outcomes.
- Phosphatidylcholine involvement in RBC-CDKI interactions improves PFS prediction when combined with clinical data.

## Abstract

The association of immuno-inflammatory parameters, especially RBC balanced signatures, with survival outcomes and adverse events still require investigation for advanced breast cancer (ABC) patients receiving cyclin-dependent kinase 4/6 inhibitor (CDKI). Herein, RBC balanced immuno-inflammatory (RBC-IMM) score was developed and capable of predicting progression-free survival (PFS) events (p < 0.001), death (p < 0.001) and grade 3/4 leukopenia (p = 0.010). RBC-IMM score also predicted PFS more accurately than classical-IMM score (AUC = 0.766 and 0.596 respectively, p = 0.005). Besides, clinico+RBC_index exhibited superior performance to clinico_index for 18-month PFS through machine learning (training set: AUC = 0.830 and 0.764 respectively; testing set: AUC = 0.894 and 0.715 respectively). Additionally, liquid chromatography-tandem mass spectrometry identified phosphatidylcholine notably involved in RBC-CDKI interaction, contributing to the construction of clinico+PtdCho_index with better PFS prediction than clinico_index (AUC = 0.854 and 0.733 respectively). These findings indicate that RBC-IMM related parameters have the advantage of identifying benefit and safety in CDKI-treated ABC patients over classical indicators.

•RBC-IMM score is calculated by the count of classical immunocytes balanced by RBC•RBC-IMM score predicts prognosis and toxicity in ABC patients on CDK4/6 inhibitor•Phosphatidylcholine may be involved in the interplay between RBC and CDK4/6 inhibitor

RBC-IMM score is calculated by the count of classical immunocytes balanced by RBC

RBC-IMM score predicts prognosis and toxicity in ABC patients on CDK4/6 inhibitor

Phosphatidylcholine may be involved in the interplay between RBC and CDK4/6 inhibitor

Cancer; Metabolomics