Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2-positive breast cancer in the adaptively randomized I-SPY2 trial.

Ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel plus trastuzumab and pertuzumab (THP) are two of the experimental regiments evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer. In pre-defined analyses we assessed 10 biomarkers at the pre-treatment timepoint in the HER2, ER/PR, and proliferation pathways to test their association with pCR (complete pathologic response). Fresh-frozen pre-treatment breast cancer tumors (n=127: 52 TDM1/P arm, 44 THP arm, 31 TH control arm) from the neoadjuvant ISPY2 trial for high risk, early-stage breast cancer were assayed using GPL16233 (n=22) or GPL20078 (n=105) expression arrays; and these data were combined into a single gene-level dataset after batch-adjusting using ComBat. The sample characteristics and their values represent: HER2: the status of the HER2 gene. 1 = positive; 0 = negative. HR: the status of hormone (estrogen and progesterone) receptors 1 = positive; 0 = negative. pCR: the status of a pathological complete response (pCR) 1 = complete response; 0 = failed complete response MP: MammaPrint status 0 = MammaPrint high 1 (MP1); 1 = MammaPrint (ultra) high 2 (MP2) Arm: arm of the trial per patient - 'T-DM1/P arm', 'THP arm', or 'TH Control'. Originally, a ComBat batch correction process was applied to the raw data on a larger group of patients (~900), which we cannot release. Linear adjustment factors from this group were derived so they can be applied to this smaller group of 127 patients. The ISPY2_LinearFit_forCombiningExp files contain linear adjustments to go from raw to batch corrected data. For fully normalized and batch corrected data on the gene level, please use ISPY2ResID_THP_TDM1P_Ctr_ExpDat_GeneLevel_n127.txt, provided in the supplementary files. For biomarkers/signatures used in the manuscript, please see supplemental data file in the manuscript.