J Breast Cancer.  2013 Mar;16(1):32-39.

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

• Lee HJ
• Seo JY
• Ahn JH
• Ahn SH
• Gong G

Abstract

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.

Keyword

Breast neoplasms; Lymphocytes; Neoadjuvant therapy; T-cell

MeSH Terms

Biopsy
Breast
Breast Neoplasms
Humans
Lymphocyte Count
Lymphocytes
Multivariate Analysis
Neoadjuvant Therapy
Polymerase Chain Reaction
Receptor, Epidermal Growth Factor
Receptor, erbB-2
Retrospective Studies
T-Lymphocytes
Receptor, Epidermal Growth Factor
Receptor, erbB-2

Figure

• 

  Figure 1 Histological patterns of lymphocyte infiltration into breast cancer tissue relative to the response to neoadjuvant chemotherapy. High-level lymphocyte infiltration was evident in a patient with pathologic complete response (pCR) (H&E, A: ×100, B: ×200). Lymphocyte infiltration was sparse in another patient who did not show pCR (H&E, C: ×100, D: ×200).

• 

  Figure 2 Immunohistochemical staining of CD3, CD8, and forkhead box P3 (FOXP3) in breast cancer samples. Heavy infiltration of CD3+, CD8+, and FOXP3+ cells was observed in a patient who achieved pathologic complete response (pCR) (A-C, ×200). Only a few CD3+, CD8+, and FOXP3+ lymphocytes were observed, in a scattered manner, in the microscopic fields of a tissue sample from a patient who did not attain pCR (D-F, ×200).

• 

  Figure 3 Percentages of pathologic complete response (pCR) in patient groups divided by lymphocyte infiltration. The pCR rate increased as the peritumoral space became increasingly infiltrated by lymphocytes (A-C).

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