Whole-Lesion Histogram Analysis of the Apparent Diffusion Coefficient as a Quantitative Imaging Biomarker for Assessing the Level of Tumor-Infiltrating Lymphocytes: Value in Molecular Subtypes of Breast Cancer

Abstract

PurposeTo assess whether apparent diffusion coefficient (ADC) metrics can be used to assess tumor-infiltrating lymphocyte (TIL) levels in breast cancer, particularly in the molecular subtypes of breast cancer.MethodsIn total, 114 patients with breast cancer met the inclusion criteria (mean age: 52 years; range: 29–85 years) and underwent multi-parametric breast magnetic resonance imaging (MRI). The patients were imaged by diffusion-weighted (DW)-MRI (1.5 T) using a single-shot spin-echo echo-planar imaging sequence. Two readers independently drew a region of interest (ROI) on the ADC maps of the whole tumor. The mean ADC and histogram parameters (10th, 25th, 50th, 75th, and 90th percentiles of ADC, skewness, entropy, and kurtosis) were used as features to analyze associations with the TIL levels in breast cancer. Additionally, the correlation between the ADC values and Ki-67 expression were analyzed. Continuous variables were compared with Student’s t-test or Mann-Whitney U test if the variables were not normally distributed. Categorical variables were compared using Pearson’s chi-square test or Fisher’s exact test. Associations between TIL levels and imaging features were evaluated by the Mann-Whitney U and Kruskal-Wallis tests.ResultsA statistically significant difference existed in the 10th and 25th percentile ADC values between the low and high TIL groups in breast cancer (P=0.012 and 0.027). For the luminal subtype of breast cancer, the 10th percentile ADC value was significantly lower in the low TIL group (P=0.041); for the non-luminal subtype of breast cancer, the kurtosis was significantly lower in the low TIL group (P=0.023). The Ki-67 index showed statistical significance for evaluating the TIL levels in breast cancer (P=0.007). Additionally, the skewness was significantly higher for samples with high Ki-67 levels in breast cancer (P=0.029).ConclusionsOur findings suggest that whole-lesion ADC histogram parameters can be used as surrogate biomarkers to evaluate TIL levels in molecular subtypes of breast cancer.