Effect of MR Imaging Contrast Thresholds on Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes: A Subgroup Analysis of the ACRIN 6657/I-SPY 1 TRIAL.

Wen Li,Vignesh Arasu,Jessica Gibbs,John Kornak,Laura Esserman,Bonnie Joe,Lisa Wilmes,Ella Jones,Nola Hylton,David Newitt

doi:10.18383/j.tom.2016.00247

Abstract

Functional tumor volume (FTV) measurements by dynamic contrast-enhanced magnetic resonance imaging can predict treatment outcomes for women receiving neoadjuvant chemotherapy for breast cancer. Here, we explore whether the contrast thresholds used to define FTV could be adjusted by breast cancer subtype to improve predictive performance. Absolute FTV and percent change in FTV (ΔFTV) at sequential time-points during treatment were calculated and investigated as predictors of pathologic complete response at surgery. Early percent enhancement threshold (PEt) and signal enhancement ratio threshold (SERt) were varied. The predictive performance of resulting FTV predictors was evaluated using the area under the receiver operating characteristic curve. A total number of 116 patients were studied both as a full cohort and in the following groups defined by hormone receptor (HR) and HER2 receptor subtype: 45 HR+/HER2−, 39 HER2+, and 30 triple negatives. High AUCs were found at different ranges of PEt and SERt levels in different subtypes. Findings from this study suggest that the predictive performance to treatment response by MRI varies by contrast thresholds, and that pathologic complete response prediction may be improved through subtype-specific contrast enhancement thresholds. A validation study is underway with a larger patient population.

Highlights

Breast cancer, the most common type of cancer among women, is a heterogeneous disease comprising subtypes with different biology, prognosis, and treatment outcome
We explored how the pathological complete response (pCR) prediction performance of Functional tumor volume (FTV) varies over a wide range of percent enhancement threshold (PEt) and signal enhancement ratio threshold (SERt), for different serial time-point Magnetic resonance imaging (MRI) scans during the neoadjuvant (preoperative) chemotherapy (NACT) course, and for different patient cohorts determined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status
We show that the predictive performance to treatment response by MRI varies by contrast thresholds, and that the pCR prediction may be improved through subtype-specific contrast enhancement thresholds

Summary

Introduction

The most common type of cancer among women, is a heterogeneous disease comprising subtypes with different biology, prognosis, and treatment outcome. Breast cancer can be classified into subtypes based on the hormone receptor (HR) status, including both estrogen and progesterone receptors, and human epidermal growth factor receptor 2 (HER2) expression to inform treatment decisions [1, 2] These breast cancer subtype classifications have implications for disease-free survival and relapse [3]. Previous studies have found that the tumor volume measured using MRI for patients undergoing preoperative chemotherapy has strong association with recurrence-free survival [13, 15, 16], and the association is influenced by the threshold settings of 2 contrast enhancement parameters [17] Another recent study has demonstrated that the influence varied in HR/HER2− defined breast cancer subtypes [18]

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