Abstract
Background
Patients with triple-negative breast cancer who obtain a pathological complete response after neoadjuvant chemotherapy have an improved prognosis. The existence of tumour-infiltrating lymphocytes (TILs) in breast cancer is also an independent prognostic factor, and lymphocyte-predominant breast cancer is more likely to respond to neoadjuvant chemotherapy. However, the detailed composition of immune cell infiltration in breast cancer and its relationship to the response to neoadjuvant chemotherapy has not been fully investigated.
Methods
The level of infiltration by immune cells expressing representative immune cell lineage surface markers in pre-treatment biopsy specimens from 52 patients with triple-negative breast cancer who received neoadjuvant chemotherapy and underwent curative surgery were examined by multispectral immunofluorescent labelling. The immune-related cell-surface markers, CD8, CD4, CD19, CD14, CD11c, and CD11b were selected. The numbers of infiltrating immune cells of each phenotype were counted and their association with pathological treatment response to neoadjuvant chemotherapy and patient outcome were analysed.
Results
The level of CD8-positive TIL infiltration was significantly higher in patients with a pathological complete response than in those without (P = 0.045). Although not statistically significant, stratified analysis showed high levels of CD8-positive TIL infiltration were associated with a high pathological complete response rate in the subgroup that also had high CD4-positive TIL infiltration. The Cox proportional hazard model revealed that only lymph node involvement was associated with disease-free survival (P = 0.008). The subgroup with high levels of CD8-positive TIL infiltration was related to a significantly prolonged disease-free survival in node-positive patients (P = 0.02), but not in node-negative patients (P = 0.73).
Conclusion
Our data suggest that assessing the infiltration of CD8-positive TILs in the primary tumour is a useful biomarker for prediction of pathological complete response after neoadjuvant chemotherapy and improved outcome in node-positive patients.