Biomarker assessments
Hormone receptor-positive disease, tumor, death
DISEASE, TUMOR
Biomarker analyses were conducted on formalin-fixed paraffin-embedded tumor tissue collected at baseline for all markers (Additional file Expression of additional predefined single genes and signatures of interest were analyzed using a custom 800-gene codeset on the nCounter® platform (NanoString Technologies) from samples collected at baseline, cycle 2, and surgery. Genes of interest included HER2, programmed death ligand 1 (PD-L1), CD8, predefined immune signatures including 3-gene (PD-L1/IFNG/CXCL9), 5-gene (PD-L1/granzyme B/CD8/IFNG/CXCL9), T effector (Teff) signature (CD8/granzyme A/granzyme B/perforin/IFNG), chemokine signaling (ThCytokines signature, i.e., CXCL9/CXCL10/CXCL11), and checkpoint inhibitor signatures (PD-L1/PD-L2/IDO), as well as other markers of interest (complete listing available in Additional file The Prediction Analysis of Microarray with the 50-gene classifier (PAM50) subtype prediction [Expression of PD-L1 by IHC was assessed post hoc (Ventana SP142 assay, Roche Diagnostics) from samples collected at baseline, cycle 2, and surgery. PD-L1-positive disease was defined as tumor-infiltrating immune cell (IC) expression ≥ 1% of the tumor area (IC score 1, 2, or 3), while PD-L1-negative disease was defined as PD-L1 expression on IC < 1% of the tumor area (IC score 0) [Local hormone receptor status was assessed as a stratification factor, and centrally assessed hormone receptor status was used for the biomarker analyses. Hormone receptor-positive disease was defined as estrogen and/or progesterone receptor staining of ≥ 1% (Dako Omnis IHC assay, Agilent Technologies).FcγR IIa (rs1801274), FcγR IIIa (s396991), ABCB1 polymorphisms (RS1045642), and ABCG2 polymorphisms (RS2231142) were analyzed based on whole blood samples collected at baseline or during the study. Polymorphisms were assessed using genotyping assays from ThermoFisher and TaqMan probe chemistry.All biomarkers were analyzed for their correlation with pCR. In addition, specific biomarkers (HER2 IHC subgroups, 