Abstract P3-04-10: The TILs-US score adding vascularity assessment based on ultrasonography for predicting tumor-infiltrating lymphocytes in human epidermal growth factor receptor 2-positive and triple-negative breast cancer
Authors: Kimura Yuri , Masumoto Norio , Akashi-Tanaka Sadako , Fukui Kayo , Noma Midori , Nagata Aya , Nakamura Takashi , Shima Hiroaki , Okuno Toshitaka , Murakami Akari , Kamei Yoshiaki , Nakano Shogo , Arihiro Koji 
Published: March 2023

Background: Tumor-infiltrating lymphocytes (TILs) are a useful prognostic factor and predictive biomarker of neoadjuvant chemotherapy treatment response for breast cancer, especially in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer and triple-negative breast cancer (TNBC). However, due to heterogeneity of TIL expression and distribution in the tissues, accurately predicting TIL expression, especially using limited core-needle biopsy specimens, is difficult. Therefore, an accurate and simple preoperative evaluation method is needed. We have reported that the TILs-ultrasonography (US) score determined by characteristic US findings has a predictive performance for lymphocyte-predominant breast cancer (LPBC). This study aimed to investigate whether the TILs-US score with added vascularity assessment has a better predictive performance for LPBC.

Methods: This multicenter, retrospective study investigated the validation and scoring of the LPBC characteristic imaging findings and applied it for LPBC and non-LPBC prediction. A total of 100 patients with HER2-positive breast cancer (n = 59) and TNBC (n = 41) treated by curative surgery between January 2014 and December 2021 were evaluated. Stromal lymphocytes in surgical pathological specimens were evaluated; the cutoff value for predicting LPBC was defined as ≥50% stromal TILs. Preoperative US was examined for TIL indicators. The US images with characteristic TILs were scored for LPBC prediction. Univariate and multivariate logistic regression analyses were employed for each potential predictor variable of LPBC.

Results: A total of 40 patients with ≥50% stromal TILs were defined as having LPBC. The examined characteristic US findings for predicting LPBC, shape (more lobulated), internal echo level (weaker), posterior echoes (stronger), and vascularity assessment (hypervascularity), were significantly associated with LPBC and used to assign the scoring for predicting LPBC. As previously reported, the TILs-US score ranged from 0–7 points based on three ultrasonic tissue characteristics: shape (round, oval, and polygonal or irregular, 0 points; lobulated, 1 point; and small lobulated, 2 points), internal echo level (high or equal, 0 points; low, 1 point; and extremely low, 2 points), and posterior echoes (shadowing or attenuating, 0 points; no change, 1 point; accentuated, 2 points; and extremely accentuated, 3 points). We further added vascularity assessment (avascular or hypovascular, 0 point; moderately vascular, 1 point; and hypervascular, 2 points) to this scoring system. Based on the receiver operating characteristics (ROC) curves (AUC [Area Under the Curve] 0.77), the score cutoff for predicting LPBC was 4 points for TILs-US score (sensitivity, 0.83; specificity, 0.55; and accuracy, 0.66). Multivariate logistic regression analysis revealed that cT (&lt; T2), estrogen receptor (ER) negativity, and a TILs-US score of ≥4 points were significant LPBC predictors (odds ratio [OR] 3.60; p = 0.028; OR 8.68; p = 0.020; OR 5.99; p = 0.005). Conversely, based on the ROC curves (AUC 0.78), the score cutoff for predicting LPBC was 5 points after adding vascularity assessment (sensitivity, 0.93; specificity, 0.57; and accuracy, 0.71). Multivariate logistic regression analysis revealed that cT (&lt; T2), ER negativity, and a TILs-US score adding vascularity assessment of ≥5 points were significant LPBC predictors (OR 5.12; p = 0.010; OR 10.3; p = 0.019; OR 20.1; p &lt; 0.001).

Conclusions: Including the vascularity assessment to the TILs-US score, which can be noninvasively obtained using US, is a more accurate preoperative predictor of LPBC. Vascularity assessment may be an auxiliary factor in predicting LPBC.

Univariate and multivariate logistic analysis of significant clinicopathological factors predicting lymphocyte-predominant breast cancer.

Citation Format: Yuri Kimura, Norio Masumoto, Sadako Akashi-Tanaka, Kayo Fukui, Midori Noma, Aya Nagata, Takashi Nakamura, Hiroaki Shima, Toshitaka Okuno, Akari Murakami, Yoshiaki Kamei, Shogo Nakano, Koji Arihiro. The TILs-US score adding vascularity assessment based on ultrasonography for predicting tumor-infiltrating lymphocytes in human epidermal growth factor receptor 2-positive and triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-10.