Abstract P5-16-05: MINT trial yields MammaPrint High1/High2 risk classes associated with significant differences in pCR and receptor subtype
Authors: Blumencranz LE , Shivers SC , Untch S , Treece TD , Yoder E , Blumencranz PW , Cox CE 
Published: March 2017

Abstract
Background: Previous clinical trials have validated that the 70-gene signature MammaPrintTM provides prognostic and predictive information for early stage breast cancer patients and can identify low risk patients who may safely avoid adjuvant chemotherapy. Additionally, the neo-adjuvant I-SPY 1&2 TRIALs demonstrated that further stratification of patients into MammaPrint High 1 (MP1) and MammaPrint High 2 (MP2) risk groups may help predict chemo-sensitivity. There were significant differences in pathological complete response (pCR) rates for early stage, locally advanced breast cancer patients who were not HR+HER2- MammaPrint Low Risk. Specifically, the PARP inhibitor veliparib in combination with carboplatin recently graduated the I-SPY 2 phase 2 screening trial, having met the 85% predictive probability criterion with a triple-negative breast cancer signature, which was the subset recommended for this regimen's subsequent development. Given these data, we wanted to determine whether the Multi Institutional Neo Adjuvant Therapy MammaPrint Project (MINT) patient population confirmed the MP1/MP2 risk stratification, clarify if there is an associated receptor subtype for MP1/MP2 risk classes, and conclude if the stratification correlates to a significant difference in pCR. Methods: Array data from pre-treatment samples were obtained from 180 patients classified as MammaPrint High Risk, subtyped by IHC and treated with neo-adjuvant chemotherapy according to protocol. Response was measured by centrally assessed residual cancer burden pursuant to guidelines. Patients were then further stratified based on the MammaPrint Index per their classification threshold between MP1/MP2. Fisher's exact test was used to assess significance of association with pCR overall and within hormone receptor (HR) and HER2 subtypes. Results: MP1 vs MP2 risk classes yielded subsets with significant (p=0.007) differences in pCR. 44% (40/92) of MP2 patients achieved a pCR, compared to 24% (21/88) of MP1 patients. Next, we investigated whether the MP1 and MP2 risk classes were associated with receptor subtype. MP1 demonstrated a significant association and MP2 near significance. 32% (21/66) of triple-negative patients were classified as MP2 vs only 3% (2/66) MP1. Similarly, in the overall population, 28% (51/180) HR+HER2- are classified as MP1 vs 4% (8/180) MP2. Results in the pCR population were reflective of these subtype trends. 63% (58/92) of MP2 patients were classified triple-negative, of which nearly one quarter (21/92) had a measured pCR, whereas 58% (51/88) of MP1 patients were HR+HER2- with 3% (3/88) achieving pCR (Table1). Conclusion: This analysis in the MINT patient population supports previously published data and suggests that the MammaPrint High 1/2 risk classification may help predict chemo-sensitivity. Given the statistical significance of these data, we are currently investigating the biological mechanisms distinguishing the MP1/MP2 subgroups that may account for its use as a specific biomarker of response to chemotherapy treatment in future trials.
Table 1.MP1MP2HER2+HER2-HER2+HER2-HR+HR-HR+HR-HR+HR-HR+HR-793241322185486456371514518818858Row#1= pCR, #2= RD, #3= Total
Citation Format: Blumencranz LE, Shivers SC, Untch S, Treece TD, Yoder E, Blumencranz PW, Cox CE. MINT trial yields MammaPrint High1/High2 risk classes associated with significant differences in pCR and receptor subtype [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-05.