Tumor-Associated Lymphocytes Predict Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

PURPOSE Tumor-associated lymphocyte numbers in breast cancer have been suggested as a new independent predictor of response to neoadjuvant chemotherapy in breast cancer patients. We therefore evaluated the relationship between pathologic complete response (pCR) and tumor-associated lymphocytes in tumors of such patients. METHODS Between 2000 and 2009, we retrospectively evaluated 175 patients with primary breast cancer treated with neoadjuvant chemotherapy, followed by definitive surgical resection. Peritumoral lymphocytic infiltration (LI) and CD3(+), CD8(+), and forkhead box P3 (FOXP3)(+) lymphocytes were assessed in pretreatment biopsy specimens. RESULTS Nineteen (11%) patients achieved pCR. An elevated LI, CD3(+), CD8(+), or FOXP3(+) lymphocytic infiltration; lower clinical T stage; human epidermal growth factor receptor 2 overexpression; and herceptin-based treatment were all significantly associated with pCR. Through a multivariate analysis, LI (odds ratio [OR], 1.26; p=0.024), clinical T stage (OR, 3.06; p=0.041), and the use of a herceptin-based regimen (OR, 4.95; p=0.004) were all significant independent predictors of pCR. Significantly higher numbers of tumor-associated lymphocytes and CD3(+), CD8(+), and FOXP3(+) T-cells were observed in the following: high-grade tumors, tumors of positive nodal status, and tumors negative for hormone receptors. CONCLUSION Tumor-associated lymphocytes are significantly associated with pCR, suggesting that tumor-associated lymphocytes may be an important pathological factor predicting a response to neoadjuvant chemotherapy in breast cancer patients.