Therapeutic Effect of Trastuzumab in Neoadjuvant-Treated HER2-Positive Breast Cancer with Low Infiltrating Level of Tumor-Infiltrating Lymphocytes.

Purpose: The aim of the present study was to investigate the effect of trastuzumab on the pathological complete response (pCR) rate and event-free survival (EFS) in neoadjuvant-treated HER2-positive breast cancer with a low infiltrating level of tumor-infiltrating lymphocytes (TILs). Patients and Methods: The infiltrating level of TILs was evaluated in hematoxylin and eosin-stained slides from diagnostic needle biopsies, and a low infiltrating level of TILs was defined as TILs < 10%. Data of 179 HER2-positive patients with a low infiltrating level of TILs were retrospectively reviewed and compared according to whether trastuzumab was administered or not. The associations of clinicopathological characteristics with pCR or EFS were assessed in univariate and multivariate analyses. EFS was estimated by the Kaplan-Meier method and compared by the log rank test. Results: Of 179 patients, the overall pCR rate was 20.1%, and 74 patients (41.3%) received trastuzumab. Patients treated with trastuzumab showed a pCR rate of 20.3% compared with 20.0% for those without trastuzumab (P = 0.965). Trastuzumab administration was not associated with pCR in univariate (P = 0.965) and multivariate (P = 0.994) analyses. Negative status of hormone receptor (HR) (P < 0.001) and histological grade 3 (P = 0.007) were independent predictors for pCR in multivariate analyses. Trastuzumab usage had no significant impact on EFS in univariate (P = 0.916) and multivariate (P = 0.431) analyses, and pCR was the only independent predictor for favorable EFS (P = 0.012) in multivariate analyses. Conclusion: In neoadjuvant-treated HER2-positive breast cancer with a low infiltrating level of TILs, additional trastuzumab had no significant influence on the pCR rate and EFS. HR-negative status and histological grade 3 were independently associated with higher pCR rates, and pCR was the only independent predictor for improved survival. Our findings may help identify patients who are resistant to trastuzumab, thereby guiding the de-escalating choice of anti-HER2 therapy.