Combined use of MammaPrint and molecular subtyping profile (BluePrint) to identify subgroups with marked differences in response to neoadjuvant treatment.

Abstract

42 Background: Concordance between the IHC receptor status and the molecular subtype suggests that molecular profiles represent oncogenic processes that are driven by pathways in which ER, PR and HER2 play pivotal roles. It is, therefore, likely that the use of gene expression arrays will enable the identification of previously unappreciated subtypes of breast cancer that differ in clinical outcomes. Methods: The cohort consists of 133 (T1-4, N0-3) breast cancer patients treated with T/FAC neoadjuvant chemotherapy. Genome wide expression data was publicly available and downloaded from bioinformatics.mdanderson.org/pubdata.html. The data was used to determine the response to T/FAC neoadjuvant chemotherapy for patients stratified by MammaPrint and molecular subtype (BluePrint). The MammaPrint and BluePrint result were used to subtype the patients into 4 groups: MammaPrint Low-risk/Luminal-type, MammaPrint High-risk/Luminal-type, Basal-type and ERBB2-type. Results: Within this patient cohort, 20% (n=27) were classified as Basal-type, 62% (n=82) as Luminal-type, and 18% (n=24) as ERBB2-type. The overall pCR of this patient cohort was 26% and differed substantially among the subgroups. pCR was observed in 9% of all Luminal-type samples (i.e. 3% of MammaPrint Low Risk/Luminal-type and 11% of MammaPrint High Risk/Luminal-type), in 50% of the ERBB2-type samples and in 56% of the Basal-type samples. The pCR rates observed for the ERBB2-type and Basal-type patient groups were higher compared to classification based on IHC/CISH assessed ER and HER2 receptor status: 50% for ERBB2-type versus 39% for HER2+ and 56% for Basal-type versus 47% for ER-/HER2- samples. Conclusions: We observed marked differences in response to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint. These findings confirm differences in chemotherapy response among molecular subgroups and indicate that the BluePrint profile described here will help to further establish a clinical correlation between molecular subtyping and treatment response.