The Relationship Between Tumor-infiltrating Lymphocytes And Clinicopathological Characteristics And Prognosis Of Breast Cancer

Background:Breast cancer is the most common form of cancer diagnosed in women. In2013, it has accounted for29%of all new cancer cases and14%of all cancer deaths among women, worldwide. Multi-stage and multiple genes involved in the recurrence and metastasis of breast cancer, it is a dynamic process. Traditional cancer research focus on tumor cells themselves, want to use genetic and phenotypic change to explain the tumors progress, but in recent years, researches has found that tumor microenvironment plays an essential role in the process of destruction of normal tissue such as tumor growth, invasion and metastasis. In tumor microenvironment, tumor infiltrating lymphocytes may play a pivotal role in the evolution of malignant tumor. The latest research also proved that tumor infiltrating lymphocytes have effect on the characteristics and prognosis of breast cancer. So we have done a meta-analysis to investigate the relationship between tumor infiltrating lymphocytes and the clinical pathological characteristics and prognosis of breast cancer. Methods:A comprehensive search strategy was used to search relevant literature in PubMed, MEDLINE and the ISI Web of Science, by using the following tags:"tumor-infiltrating lymphocytes and breast cancer" or "tumor-associated lymphocytes and breast cancer". The correlation between Tumor-infiltrating lymphocytes and clinicopathological features and breast cancer prognosis was analyzed. This meta-analysis was carried out using Review Manager5.2.Result:Eighteen eligible studies consisting of12,805participants were included. We found that total tumor-infiltrating lymphocytes have no relationship with breast cancer grade、expression of hormone receptor and human epidermal growth factor receptor-2, some subtype of tumor infiltrating lymphocytes were associated with breast cancers clinicopathological features, such as higher PD-1+TIL values were observed in patients with HR (-)(pooled RR=1.34,95%CI:1.18-1.52, Z=4.60, P=0.000and I2=0fixed-effect), HER-2(+)(pooled RR=0.65,95%CI:0.46-0.92, Z=2.42, P=0.02and I2=9%fixed-effect). Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in breast cancer(pooled RR=0.49,95%CI:0.39-0.61, Z=6.49, P=0.000and I2=45%fixed-effect), except for the patients with negative expression of hormone receptor(pooled RR=0.79,95%CI:0.59-1.06, Z=1.57, P=0.12and I2=44%fixed-effect). The over-expression of total tumor-infiltrating lymphocytes was associated with better prognosis, but without statistical significance(RR=0.88,95%CI=0.67-1.16, Z=0.88, P=0.38and I2=63%random-effect). While, some subtype of TIL infiltrating in breast cancer revealed a worse result, like PD-1+TIL or Foxp3+TIL.Conclusion:1、Our meta-analysis showed that total tumor-infiltrating lymphocytes were not associated with breast cancers clinicopathological features, but some subtype may have the relationship.2、higher values of tumor-infiltrating lymphocytes predict a good response to neoadjuvant chemotherapy in breast cancer, except of the hormone receptor negative patients.3、total tumor-infiltrating lymphocytes was significantly associated with better prognosis, but without statistical significance, but several subtype revealed a worse result.