Human Epidermal Growth Factor Receptor Type 2-Positive Breast Cancer: Association of MRI and Clinicopathologic Features With Tumor-Infiltrating Lymphocytes

Background: Tumor-infiltrating lymphocytes (TILs) are associated with therapeutic outcomes and prognosis in patients with human epidermal growth factor receptor type 2-positive (HER2+) breast cancer. Identification of TIL levels is clinically relevant. Objective: To explore associations of clinicopathologic and MRI features with TIL levels in patients with HER2+ breast cancer. Methods: A total of 212 consecutive women (mean age, 54 years) diagnosed with HER2+ breast cancer between January 2017 and December 2019 were included in this retrospective study. Patients were divided into low (<10%) and high (≥10%) TIL groups. Three breast radiologists independently reviewed images; interreader agreement was assessed, and the first readers' findings were used for further analysis. Associations of clinicopathologic and MRI features with TIL levels were evaluated using multivariable logistic regression analysis. Subanalysis of TIL levels by hormone receptor (HR) status was also performed. Results: A total of 115 (54.2%) patients had low, and 97 (45.8%) had high, TIL levels. High TIL level was associated (all p<.05) with histologic grade 3 (odds ratio [OR]=3.98; frequency of 78.4% vs 52.2% in high vs low TIL groups, respectively), high tumor cellularity (OR=4.59; median cellularity of 60% vs 50%), lower frequency of associated ductal carcinoma in situ (OR=0.16; frequency of 86.6% vs 94.8%), and higher frequency of peritumoral edema on T2-weighted images (OR=2.83; 71.1% vs 50.4%). In subgroup analysis by HR status, histologic grade 3 (OR=5.03, p=.002) was a significant independent predictor of high TIL in the HR+/HER2+ group, while high tumor cellularity (OR=9.06, p=.002), peritumoral edema (OR=5.23, p=.03), and low ADC (OR=11.69, p=.047) were independent predictors of high TIL in the HR-/HER2+ group. Interreader agreement for peritumoral edema was moderate among the three radiologists (к, range 0.432-0.539). Conclusion: Peritumoral edema on MRI and histopathologic feature of tumor aggressiveness help predict high TIL levels in patients with HER2+ breast cancer. Clinical Impact: Pretreatment MRI features may serve as a useful tool for assessing TIL levels in patients with HER2+ breast cancer, helping to classify patients with variable clinical outcomes related to immune activity and to guide selection among neoadjuvant chemotherapy (NAC) or HER2-targeted therapy or immunotherapy.