Tumor-associated lymphocytes predict response to neoadjuvant chemotherapy in breast cancer patients - PubMed (original) (raw)
Tumor-associated lymphocytes predict response to neoadjuvant chemotherapy in breast cancer patients
Hee Jin Lee et al. J Breast Cancer. 2013 Mar.
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.
Keywords: Breast neoplasms; Lymphocytes; Neoadjuvant therapy; T-cell.
Conflict of interest statement
The authors declare that they have no competing interests.
Figures
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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References
- Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003;21:4165–4174. - PubMed
- Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15:2483–2493. - PubMed
- Abrial SC, Penault-Llorca F, Delva R, Bougnoux P, Leduc B, Mouret-Reynier MA, et al. High prognostic significance of residual disease after neoadjuvant chemotherapy: a retrospective study in 710 patients with operable breast cancer. Breast Cancer Res Treat. 2005;94:255–263. - PubMed
- Tewari M, Krishnamurthy A, Shukla HS. Predictive markers of response to neoadjuvant chemotherapy in breast cancer. Surg Oncol. 2008;17:301–311. - PubMed
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