Abstract P6-09-45: Long-term follow-up of early stage breast cancer patients with results of MammaPrint®, Oncotype DX® and MammoStrat® risk classification assays
Authors: Shivers SC , Russell S , Blumencrancz L , Mehindru A , Acs G , Ellis D , Vrcelj V , Zanchi A , Blumencrancz PW , Carter E , King J , Cox CE 
Published: March 2017

Abstract
Introduction: The use of genomic tests for the prediction of breast cancer recurrence is becoming more common. MammaPrint® (MP, Agendia Inc.) is a 70-gene microarray assay designed to assess the 10-year risk of recurrence in an untreated population that was not selected for ER/HER2 results. The Oncotype DX® Recurrence Score® (RS, Genomic Health, Inc.) is a 21-gene RT-PCR assay that is clinically validated to predict the 10-year risk of distant recurrence in ER+ patients treated with Tamoxifen. MammoStrat® (MS, Clarient, Inc.) is an IHC assay that uses 5 antibodies and has been validated in a similar population as RS. Several recent reports show that these assays classify patients differently with significant discordances for all risk groups (Shivers, et al., SABCS 2013; Denduluri, et al., ASCO Breast 2011; Poulet, et al., SABCS 2012; Schneider, et al., ASCO 2013). The present study is an analysis of long-term follow-up in a cohort of patients who have results for all three of these risk-stratifying assays side by side in the same samples.
Methods: Patients with ER+ N0-N1 early-stage breast cancer with an MP result obtained as part of their routine clinical care were identified at the University of South Florida (USF, N=65) and Morton Plant Hospital (N=83). After local IRB approval, slides and/or blocks were cut and de-identified at USF and sent to Genomic Health and Clarient for blinded testing. Clinicopathological features were also reviewed by 3 breast pathologists.
Results: 148 patients with an MP result had tissue available to send for RS and MS assays. These patients had a median age of 62 years; median tumor size 1.8 cm; 9% low grade, 59% intermediate grade and 32% high grade. In our previous analysis of this study, of 148 patients with MP results, 53% were low risk and 47% were high risk. Of 135 samples that yielded enough RNA to produce an RS result, 53% were low risk, 26% were intermediate risk and 21% were high risk. Of 129 samples that yielded an MS result, 44% were low risk, 28% were moderate risk and 28% were high risk. Of 121 patients with results for all 3 assays, only 22% were concordant for low risk and 9% were concordant for high risk across all 3 assays. Overall, 30% of cases showed a major discordance such as low risk for one assay and high risk for another. After median follow-up of 54 months, 9 patients have had a distant metastasis and/or 8 patients have died (11 patients total). One patient who had bone metastasis and died had been classified as low risk by all 3 assays. Three patients with distant metastases had a major discordance between assays, with two high risk and one low risk result. Seven patients were classified as high or intermediate/moderate risk by all 3 assays.
Conclusions: This direct comparison demonstrates that although the assays classify a large proportion of patients differently, the patients who ended up with a distant metastasis and/or died of breast cancer had been classified as high risk by at least two of the three assays. This study has important clinical implications since these assays are used to help make treatment decisions regarding which patients might benefit from chemotherapy.
Citation Format: Shivers SC, Russell S, Blumencrancz L, Mehindru A, Acs G, Ellis D, Vrcelj V, Zanchi A, Blumencrancz PW, Carter E, King J, Cox CE. Long-term follow-up of early stage breast cancer patients with results of MammaPrint®, Oncotype DX® and MammoStrat® risk classification assays [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 P6-09-45.