Molecular subtyping predicts pathologic tumor response in early-stage breast cancer treated with neoadjuvant docetaxel plus capecitabine with or without trastuzumab chemotherapy.

Abstract

The purpose of this study was to assess the correlation of the pathologic complete response (pCR) and near-complete pathologic response (npCR) between gene expression profiling using either the dataset of 150 genes as determined by BluePrint/MammaPrint versus PAM50 molecular subtyping. The samples were from patients with operable early-stage breast cancer prior to neoadjuvant chemotherapy of capecitabine plus docetaxel, with or without trastuzumab. Molecular subtyping data were analyzed on samples from 122 patients enrolled in XeNA neoadjuvant trial. The biopsies were obtained as part of the original study where PAM50 assay was performed using custom-designed full genome 44,000 feature Agilent microarrays, and TP53 mutational analysis was performed on pretreatment tumor tissue using the AmpliChip TP53 assay. For the current study, clinical and pathological endpoints, TP53 mutation analysis and PAM50 results were collected through GEO at NCBI (GSE22358). MammaPrint and BluePrint outcomes were determined from the available gene expression data. The overall pCR plus npCR rate was 25% (30/122). Stratified by BluePrint/MammaPrint, patients of HER2 type had the best response (59%), while luminal A (7%) and B (9%) subtypes had the poorest. The pCR plus npCR rate in patients classified with PAM50 assay was 76% in HER2 type, 10% in luminal A type, and 5% in luminal B type. The pCR plus npCR rate [22/61 (36%)] among TP53-mutated patients was significantly higher than TP53 wild-type patients [7/54 (13%); P=0.012]. Concordance of BluePrint/MammaPrint with PAM50 molecular subtyping was only 59%. Regardless of the molecular subtype, for patient samples with concordant BluePrint/MammaPrint and PAM50 data, the pCR plus npCR rate in TP53 mutant samples was 17/39 (44%), whereas in patients whose tumors were TP53 wild type, it was 5/31 (16%). Molecular and intrinsic subtyping may provide predictive information for patients treated with docetaxel plus capecitabine±trastuzumab preoperatively, and these results need to be further evaluated. The differences between the two methodologies need clarification in a prospective manner and being compared to the standard IHC-FISH testing.