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.