Abstract PD11-08: Associations of baseline breast MRI metrics and immune infiltration with chemotherapy response in triple negative breast cancer
Authors: Kazerouni Anum S , Kennedy Laura C. , Hirano Michael , Chau Bonny , Biswas Debosmita , Vinayak Shaveta , Nyflot Matthew J. , Rahbar Habib , Dintzis Suzanne , Partridge Savannah C. 
Published: March 2022

Abstract
Introduction: In triple-negative breast cancer (TNBC), both response to neoadjuvant chemotherapy (NAC) and the degree of pre-treatment (pre-tx) tumor immune infiltration as defined by tumor-infiltrating lymphocytes (TILs) are prognostic. Improving NAC response prediction in early TNBC would provide the opportunity to consider adjustments to the NAC regimen prior to initiating therapy. Breast magnetic resonance imaging (MRI) enables noninvasive whole-tumor measurement of microenvironment features. We investigated the value of pre-tx MRI metrics in addition to TILs for the prediction of NAC response in early TNBC patients. Methods: Women with Stage I-III TNBC who underwent pre-tx clinical breast MRI and NAC at our institution (2005-2019) were retrospectively identified. Response to NAC was noted, with pathologic complete response (pCR) defined as no residual invasive cancer present within the breast. When tissue was available, diagnostic biopsy was used to quantify pre-tx TILs as deciles from 10-100% by a breast pathologist. Patients underwent pre-tx breast MRI on either a 1.5T or 3T scanner including diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) MRI. From DCE-MRI, tumor longest diameter (LD) and T stage (1-4), as well as contrast kinetics including percent enhancement (PE) at 2 minutes post-contrast and signal enhancement ratio (SER) were determined. Tumor peak PE and peak SER (representing the highest mean PE and SER, respectively, for 3×3 voxel subregions) and functional tumor volume (FTV, tumor volume exhibiting PE ≥ 50%) were calculated. Mean apparent diffusion coefficient (ADC) was calculated from DW-MRI. TIL levels and imaging features were compared between pCR and non-pCR groups by Wilcoxon rank sum test and performance for prediction of pCR was evaluated using areas under the curve (AUC) measures from receiver operating characteristic curve analysis. Results: 115 TNBC patients (median age: 49, range 26-79 years) were evaluated, of which 45 (39%) achieved pCR. The majority received an anthracycline-containing regimen. Pre-tx TILs (evaluated in N=60 with available biopsy specimens) ranged from 10% to 80% (median, 10%) and were significantly higher in pCR vs. non-pCR patients (p = 0.02, AUC = 0.63). Pre-tx lesion size on imaging was predictive of response (Table 1), with pCR patients having significantly lower LD (p &lt; 0.01, AUC = 0.68) and FTV (p = 0.01, AUC = 0.67). Peak PE was also associated with response, significantly lower in pCR patients (p = 0.04, AUC = 0.62), while SER and ADC were not (p &gt; 0.05). Stratifying by T stage, both peak PE (p = 0.03) and FTV (p = 0.05) were predictive of response in T1/T2 patients, while no imaging metrics reached significance in T3/T4 patients. Discussion: In a large cohort of TNBC patients undergoing NAC, measures of tumor size and immune infiltration were strongly predictive of NAC response. Preliminary results suggest that baseline peak PE and FTV are associated with NAC response, particularly in earlier stage TNBC patients. These findings support the utility of imaging and TILs assessments to predict response in TNBC and potentially guide NAC regimens for improved outcomes. Future work will extend these analyses to assess the value of changes in imaging metrics over the course of NAC to predict response. Acknowledgments: NIH P30CA015704, R01CA248192, and Roger E. Moe Fellowship, ASCO/CCF Hayden Family Foundation Young Investigator Award in Breast Cancer
Summary of imaging characteristics across TNBC cohort. Values indicate mean (standard deviation).Whole cohort. N=115T1/T2. N=80T3/T4. N=35pCR. N=45non-pCR. N=70pAUCpCR. N=39non-pCR. N=41pAUCpCR. N=6non-pCR. N=29pAUCLongest dimension (mm)34 (15)50 (27)&lt;0.010.6829 (11)31 (10)0.410.5561 (6)76 (20)0.060.75FTV (cm3)14.7 (17.0)31.2 (43.4)0.010.6710.4 (11.0)19.0 (20.2)0.050.6446.1 (24.5)52.0 (58.0)0.720.57Peak SER1.77 (0.26)1.78 (0.23)0.960.501.76 (0.26)1.79 (0.23)0.690.531.91 (0.19)1.78 (0.26)0.270.68Peak PE (%)234 (61)268 (69)0.040.62237 (61)275 (71)0.030.66247 (70)256 (63)1.000.5ADC(×10-3 mm2/s)1.19 (0.29)1.31 (0.36)0.180.581.16 (0.28)1.24 (0.30)0.390.561.40 (0.30)1.4 (0.43)0.900.48
Citation Format: Anum S Kazerouni, Laura C. Kennedy, Michael Hirano, Bonny Chau, Debosmita Biswas, Shaveta Vinayak, Matthew J. Nyflot, Habib Rahbar, Suzanne Dintzis, Savannah C. Partridge. Associations of baseline breast MRI metrics and immune infiltration with chemotherapy response in triple negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD11-08.