Abstract No. 
2019 San Antonio Breast Cancer Symposium
December 10-14

Breast cancer subtype specific association of pCR with MRI assessed tumor volume progression during NAC in the I-SPY 2 TRIAL

Li W, Onishi N, Newitt DC,Gibbs J, Wilmes LJ, Jones EF, Joe BN, Sit LS, Yau C, Chien A, Price E, Albain KS, Kuritza T, Morley K, Boughey JC, Brandt K, Choudhery S, Clark AS, Rosen M, McDonald ES, Elias AD, Wolverton D, Fountain K, Euhus DM, Han HS, Niell, B Drukteinis J, Lang JE, Lu J, Meisel JL, Mitri Z, Nanda R, Northfelt DW, Sanft T, Stringer-Reasor, Viscusi RK, Wallace AM, Yee D, Yung R, Asare SM, Melisko ME, Perlmutter J, Rugo HS, Schwab R, Symmans W, van 't Veer LJ, Berry DA, DeMichele A, Abe H, Sheth D, Edmiston KK, Ellis Ed, Ha R, Wynn R, Crane EP, Dillis C, Nelson M, Church A, Isaacs C, Khan QJ, Oh KY, Jafarian N, Bang D, Mullins C, Woodard S, Zamora KW, Ojeda-Fornier H, Sheth P, Hovanessian-Larsen L, Eghtedari M, Spektor M, Giurescu M, Newell MS, Cohen MA, Berman E, Lehman C, Smith W, Fitzpatrick K, Borders MH, Yang W, Dogan B, Goudreau S, Brown T, Esserman LJ, Hylton NM


In an adaptive randomized trial, when new treatment combinations are being tested, it is important to be able to identify patients who are progressing on treatment so that they can be changed to a different therapeutic regimen. We know that even within the molecularly high risk patients in I-SPY 2, there is considerable variation in biology. In this study, we will present results of using MRI-calculated functional tumor volume (FTV) to identify tumor progression for each breast cancer subtype.


Patients (n=990) enrolled in the I-SPY 2 TRIAL who were randomized to the graduated experimental drug arms or controls from 2010 to 2016 were analyzed. Four MRI exams were performed for each patient: pre-NAC (T0), after 3 weeks of NAC (T1), between regimens (T2), and post-NAC (T3). Functional tumor volume (FTV) was calculated at each exam by summing voxels meeting enhancement thresholds. Tumor progression at T1, T2 or T3 was identified by a positive FTV change relative to T0. Visual inspection was used to exclude false progression due to strong background parenchymal enhancement postcontrast, prominent vessels, motion, or insufficient image quality. pCR was defined as no invasive disease in the breast and lymph nodes. Negative predictive value for pCR was defined as:NPV=number of true non-pCRs / number of patients with MRI assessed tumor progressions, where “true non-pCRs” referred to patients who were non-pCRs at surgery and were assessed as progressors by MRI. The analysis was performed in the full cohort and in sub-cohorts defined by HR and HER2 statuses.


Out of 990 patients, 878 had pCR outcome data (pCR or non-pCR, pCR rate = 35%). Total and non-pCR numbers for each subtype, number of patients with tumor progression assessed by MRI at T1, T2, and T3, and NPVs, are shown in Table 1. In the full cohort, the NPV increased consistently over treatment, from T1 (NPV=83%) to T2 (93%), and to T3 (100%). The HER2+ cancer subtypes showed fewer MRI-assessed tumor progressions than HER2- subtypes: e.g. 10/209 (5%) vs. 108/669 (16%) at T1. NPV was 100% for HER2+ subtypes at T1 and T2 except for a single misclassification of a HR- tumor at T1. Only 6 tumor progressors, all HER2- were identified at T3, and all were confirmed at surgery as non-pCRs (NPV=100%). For HR+/HER2-, the NPV increased slightly from 89% at T1 to 91% at T2, while triple negative subtype had a more substantial increase, from 78% to 92%.


Our study showed strong association between tumor progressors assessed by MRI with true non-pCRs after NAC. For HER2+ tumors, although MRI progressors are rare, they strongly indicate non-pCR at all treatment time points, while HER2- subtypes show more accurate results later in treatment. We are evaluating MRI change at 6 weeks to determine if that time point is sufficient to predict progressors.

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