Stromal Tumor-Infiltrating Lymphocytes in Hormone Receptor-Positive/HER2 Negative Metastatic Breast Cancer.

Abstract

The immune landscape of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (HR+/HER2- mBC), the most common subtype of BC, remains understudied. This is mainly because of reduced sample acquisition opportunities from metastases as compared with primary tumors. In this study, we explored stromal tumor-infiltrating lymphocytes (sTIL) in metastatic samples collected through our post-mortem tissue donation program UZ/KU Leuven Post-mortem Tissue Donation program to Enhance Research (NCT04531696). sTIL were scored as a continuous parameter according to the international guidelines on 427 metastases and 38 primary untreated tumors acquired from 20 patients with HR+/HER2- mBC. Estrogen receptor (ER) status was evaluated on 362 metastases with a cutoff value for positivity set at 1% according to the American Society of Clinical Oncology/College of American Pathologists guidelines. Our analyses show that 54% and 15% of metastases had sTIL levels of ≥1% and ≥5%, respectively. sTIL levels tended to be lower in metastases as compared with their respective primary tumors (estimate, -2.83; 95% CI, -5.77 to 0.11; P = .07). sTIL levels were lower in metastases from invasive lobular carcinoma than in metastases from invasive breast carcinoma of no special type (estimate, -1.67; 95% CI, -2.35 to -0.98; P < .001). A loss of ER expression was observed in 14% of all metastases, yet a negative ER status was not significantly associated with increased sTIL levels. Finally, sTIL levels were significantly higher in lung and axillary lymph node metastases compared with all metastases. Although these analyses were conducted on multiple metastases obtained at the end of life after several lines of treatment, the data provide novel and valuable insights into the state of immune infiltration in patients with HR+/HER2- mBC.