Prediction of Distant Metastatic Recurrence By Tumor-Infiltrating Lymphocytes in Hormone Receptor-Positive Breast Cancer

Abstract

Background: Breast cancer subtypes are known to have different metastatic recurrence sites. Distant metastases are often observed during the post-operative course in patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer and triple-negative breast cancer, but are relatively rare in those with hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. Tumor-infiltrating lymphocytes (TILs) serve as an index to monitor tumor immune microenvironment and may possibly predict the prognosis and therapeutic effect in breast cancer. This study aimed to investigate the correlation between TIL density and recurrence site in HR+/HER2- breast cancer.Methods: Four-hundred and seventy-one patients with HR+/HER2- breast cancer underwent surgery as the first treatment and received adjuvant endocrine therapy (except adjuvant chemotherapy) at the Osaka City University Hospital from April 2007 to October 2015. Needle biopsy specimens were obtained from all patients to evaluate tumor morphology and examine TILs. Morphological assessment was conducted using conventional hematoxylin and eosin staining.Results: Breast cancer recurrence was observed in 42 patients. In patients with no TIL density, local recurrence was significantly less (p = 0.022), while distant metastases were significantly more (p = 0.015) compared to those in patients with TIL density. Therefore, for the prediction of distant metastases in HR+/HER2- breast cancer without chemotherapy, TILs could be used as predictors in univariate analysis (p = 0.015, odds ratio [OR] = 0.127), although not as independent factors (p = 0.285, OR = 0.144).Conclusions: Our findings indicate that TILs may predict distant metastatic recurrence in stages I–II of HR+/HER2- breast cancer.

Phase I study of adjuvant immunotherapy with autologous tumor-infiltrating lymphocytes in locally advanced cervical cancer

“…We further explored the correlations between the clinical response and baseline immune-related biomarkers in this clinical trial. It has been reported that the levels of patient serum cytokines, tumor mutation burden and immune checkpoints as well as the infiltrated immune cell composition may affect and predict the clinical achievement of TIL-based ACT treatment (46)(47)(48)(49)(50)(51). Here, we observed that low levels of immune inhibitory factors, such as TOX and Foxp3, and high infiltrated lymphocyte numbers in tumor tissues, as well as high baseline levels of inflammatory cytokines, may predict a clinical benefit for auto-TIL treatment.…”