The level of tumor-infiltrating lymphocytes and presence of
tertiary lymphoid structures are significant prognostic and predictive factors in primary
breast cancer. However, the understanding about differences in tumor-infiltrating lymphocytes and
tertiary lymphoid structures at various metastatic sites or between primary
breast tumors and metastatic sites is limited. A total of 335 cases of metastatic
breast cancer from four metastatic sites (lung, liver, brain, and ovary) were included. We analyzed the percentages of tumor-infiltrating lymphocytes and presence of
tertiary lymphoid structures in the primary and metastatic sites. The mean level of tumor-infiltrating lymphocytes in the lung
metastases was higher than in the liver, brain, ovary, and matched primary
tumors, while metastatic
tumors of the liver and brain showed lower levels of tumor-infiltrating lymphocytes than primary
tumors.
Tertiary lymphoid structures were only found in the lung and liver, and in cases of
brain metastases the change of
tertiary lymphoid structures from present to absent significantly affected the level of tumor-infiltrating lymphocytes in
metastases compared with that in matched primary
tumors. Patients with a lower histological grade,
hormone receptor positivity in primary
tumors and
metastases, a lower level of tumor-infiltrating lymphocytes and absence of
tertiary lymphoid structures in primary
tumors, a higher level of tumor-infiltrating lymphocytes and presence of
tertiary lymphoid structures in
metastases, and lung
metastases showed significantly better overall survival. Our results showed that metastatic
breast tumors in the lung had more tumor-infiltrating lymphocytes than did
tumors at other sites and matched primary
tumors. In addition, the presence of
tertiary lymphoid structures in metastatic sites is a critical factor for the level of tumor-infiltrating lymphocytes.