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

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 (<i>p</i> < 0.001), death (<i>p</i> < 0.001) and grade 3/4 leukopenia (<i>p</i> = 0.010). RBC-IMM score also predicted PFS more accurately than classical-IMM score (AUC = 0.766 and 0.596 respectively, <i>p</i> = 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.