乳腺癌浸润淋巴细胞对新辅助化学疗法反应的预测及与预后的关系_West China Medical Journal

Authors：

 杨菁 , 李宏江 ,  羊晓勤

四川大学华西医院甲状腺乳腺外科成都 610041;

Corresponding author：

羊晓勤, Email: laurayang1977@hotmail.com

Keywords：

乳腺癌; 肿瘤浸润淋巴细胞; 新辅助化学疗法; 预后

DOI：

10.7507/1002-0179.20150340

Video：

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Abstract Full text Figures/Tables Video References Cited by

近年来大量研究认为肿瘤浸润淋巴细胞是宿主免疫系统对肿瘤抗原存在免疫反应的标志，并且可以作为预测乳腺癌患者对蒽环/紫杉类新辅助化学疗法反应的有效指标。在三阴乳腺癌患者中，乳腺癌浸润淋巴细胞可作为一项判断预后的可靠指标。

Citation： 杨菁, 李宏江, 羊晓勤. 乳腺癌浸润淋巴细胞对新辅助化学疗法反应的预测及与预后的关系. West China Medical Journal, 2015, 30(6): 1179-1182. doi: 10.7507/1002-0179.20150340 Copy

1.	Desantis C, Ma JM, Bryan L, et al. Breast cancer statistics, 2013[J]. CA Cancer J Clin, 2014, 64(1):52-62.
2.	Pernas Simon S. Neoadjuvant therapy of early stage human epidermal growth factor receptor 2 positive breast cancer:latest evidence and clinical implications[J]. Ther Adv Med Oncol, 2014, 6(5):210-221.
3.	Rampurwala MM, Rocque GB, Burkard ME. Update on adjuvant chemotherapy for early breast cancer[J]. Breast Cancer (Auckl), 2014, 8:125-133.
4.	Bhattacharyya T, Sharma SC, Yadav BS, et al. Outcome of neoadjuvant chemotherapy in locally advanced breast cancer:atertiary care centre experience[J]. Indian J Med Paediatr Oncol, 2014, 35(3):215-220.
5.	Li Q, Liu M, Ma F, et al. Circulating miR-19a and miR-205 in serum May predict the sensitivity of luminal A subtype of breast cancer patients to neoadjuvant chemotherapy with epirubicin plus paclitaxel[J]. PLoS One, 2014, 9(8):e104870.
6.	Wang K, Deng QT, Liao N, et al. Tau expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy[J]. Tumour Biol, 2013, 34(1):33-38.
7.	Yu KD, Liu GY, Zhou XY, et al. Association of HER-2 copy number and HER-2/CEP-17 ratio with neoadjuvant taxane-containing chemotherapy sensitivity in locally advanced breast cancer[J]. Oncologist, 2012, 17(6):792-800.
8.	Tokuda E, Seino Y, Arakawa A, et al. Estrogen receptor-α directly regulates sensitivity to paclitaxel in neoadjuvant chemotherapy for breast cancer[J]. Breast Cancer Res Treat, 2012, 133(2):427-436.
9.	Kaufmann M, Hortobagyi GN, Goldhirsch A, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer:an update[J]. J Clin Oncol, 2006, 24(12):1940-1949.
10.	Jones RL, Smith IE. Neoadjuvant treatment for early-stage breast cancer:opportunities to assess tumour response[J]. Lancet Oncol, 2006, 7(10):869-874.
11.	Smith IC, Heys SD, Hutcheon AW, et al. Neoadjuvant chemotherapy in breast cancer:significantly enhanced response with docetaxel[J]. J Clin Oncol, 2002, 20(6):1456-1466.
12.	Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer[J]. J Clin Oncol, 1998, 16(8):2672-2685.
13.	Lindner JL, Loibl S, Denkert C, et al. Expression of secreted protein acidic and rich in cysteine (SPARC) in breast cancer and response to neoadjuvant chemotherapy[J]. Ann Oncol, 2015, 26(1):95-100.
14.	Chavez-Macgregor M, Brown E, Lei X, et al. Bisphosphonates and pathologic complete response to taxane-and anthracycline-based neoadjuvant chemotherapy in patients with breast cancer[J]. Cancer, 2012, 118(2):326-332.
15.	Nahleh Z. Neoadjuvant chemotherapy for "triple negative" breast cancer:a review of current practice and future outlook[J]. Med Oncol, 2010, 27(2):531-539.
16.	Chavez-Macgregor M, Litton J, Chen H, et al. Pathologic complete response in breast cancer patients receiving anthracycline-and taxane-based neoadjuvant chemotherapy:evaluating the effect of race/ethnicity[J]. Cancer, 2010, 116(17):4168-4177.
17.	Townsend KN, Spowart JE, Huwait H, et al. Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma[J]. PLoS One, 2013, 8(12):e82406.
18.	Preston CC, Maurer MJ, Oberg AL, et al. The ratios of CD8⁺ T cells to CD4⁺ CD25⁺ FOXP3⁺ and FOXP3^- T cells correlate with poor clinical outcome in human serous ovarian cancer[J]. PLoS One, 2013, 8(11):e80063.
19.	Jung IK, Kim SS, Suh DS, et al. Tumor-infiltration of T-lymphocytes is inversely correlated with clinicopathologic factors in endometrial adenocarcinoma[J]. Obstet Gynecol Sci, 2014, 57(4):266-273.
20.	Yamagami W, Susumu N, Tanaka H, et al. Immunofluorescence-detected infiltration of CD4⁺FOXP3⁺ regulatory T cells is relevant to the prognosis of patients with endometrial cancer[J]. Int J Gynecol Cancer, 2011, 21(9):1628-1634.
21.	翟志伟, 王振军. 肿瘤浸润淋巴细胞在结直肠癌中的研究进展[J]. 中华胃肠外科杂志, 2013, 16(8):797-800.
22.	Zhang J, Huang SH, Li H, et al. Preoperative lymphocyte count is a favorable prognostic factor of disease-free survival in non-small-cell lung cancer[J]. Med Oncol, 2013, 30(1):352.
23.	Issa-Nummer Y, Loibl S, Von Minckwitz G, et al. Tumor-infiltrating lymphocytes in breast cancer:a new predictor for responses to therapy[J]. Oncoimmunology, 2014, 3:e27926.
24.	徐林, 周涯, 肖代敏, 等. 乳腺癌患者CD4⁺ CD25 high CCR6⁺调节性T细胞的变化[J]. 四川大学学报:医学版, 2010, 41(3):415-419.
25.	Mohammed ZM, Going JJ, Edwards J, et al. The relationship between components of tumour inflammatory cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer[J]. Br J Cancer, 2012, 107(5):864-873.
26.	Hornychova H, Melichar B, Tomsova M, et al. Tumor-infiltrating lymphocytes predict response to neoadjuvant chemotherapy in patients with breast carcinoma[J]. Cancer Invest, 2008, 26(10):1024-1031.
27.	Topalian SL, Solomon D, Rosenberg SA. Tumor-specific cytolysis by lymphocytes infiltrating human melanomas[J]. J Immunol, 1989, 142(10):3714-3725.
28.	Baxevanis CN, Dedoussis GV, Papadopoulos NG, et al. Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer[J]. Cancer, 1994, 74(4):1275-1282.
29.	Gu-Trantien C, Loi S, Garaud S, et al. CD4☒ follicular helper T cell infiltration predicts breast cancer survival[J]. J Clin Invest, 2013, 123(7):2873-2892.
30.	Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes-dealing with the diversity of breast cancer:highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011[J]. Ann Oncol, 2011, 22(8):1736-1747.
31.	Lee HJ, Seo JY, Ahn JH, et al. Tumor-associated lymphocytes predict response to neoadjuvant chemotherapy in breast cancer patients[J]. J Breast Cancer, 2013, 16(1):32-39.
32.	Seo AN, Lee HJ, Kim EJ, et al. Tumour-infiltrating CD8⁺ lymphocytes as an Independent predictive factor for pathological complete response to primary systemic therapy in breast cancer[J]. Br J Cancer, 2013, 109(10):2705-2713.
33.	Dong DD, Yie SM, Li K, et al. Importance of HLA-G expression and tumor infiltrating lymphocytes in molecular subtypes of breast cancer[J]. Hum Immunol, 2012, 73(10):998-1004.
34.	Denkert C, Loibl S, Noske A, et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer[J]. J Clin Oncol, 2010, 28(1):105-113.
35.	West NR, Milne K, Truong PT, et al. Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer[J]. Breast Cancer Res, 2011, 13(6):R126.
36.	Ono M, Tsuda H, Shimizu C, et al. Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer[J]. Breast Cancer Res Treat, 2012, 132(3):793-805.
37.	Melichar B, Hornychová H, Kalábová H, et al. Increased efficacy of a dose-dense regimen of neoadjuvant chemotherapy in breast carcinoma:a retrospective analysis[J]. Med Oncol, 2012, 29(4):2577-2585.
38.	Apetoh L, Ghiringhelli F, Tesniere AA, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy[J]. Nat Med, 2007, 13(9):1050-1059.
39.	Bellati F, Napoletano C, Gasparri ML, et al. Immunologic systemic effect of neoadjuvant chemotherapy requires investigation before tumor-associated lymphocytes can be introduced in breast cancer treatment algorithm[J]. J Clin Oncol, 2010, 28(27):e471-e472; author reply e473.
40.	Ladoire S, Arnould L, Apetoh L, et al. Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating foxp3⁺ regulatory T cells[J]. Clin Cancer Res, 2008, 14(8):2413-2420.
41.	Demir L, Yigit S, Ellidokuz H, et al. Predictive and prognostic factors in locally advanced breast cancer:effect of intratumoral FOXP3⁺ Tregs[J]. Clin Exp Metastasis, 2013, 30(8):1047-1062.
42.	Mahmoud SM, Paish EC, Powe DG, et al. Tumor-infiltrating CD8⁺ lymphocytes predict clinical outcome in breast cancer[J]. J Clin Oncol, 2011, 29(15):1949-1955.
43.	Liu S, Lachapelle J, Leung S, et al. CD8⁺ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer[J]. Breast Cancer Res, 2012, 14(2):R48.
44.	Lim KH, Telisinghe PU, Abdullah MS, et al. Possible significance of differences in proportions of cytotoxic T cells and B-lineage cells in the tumour-infiltrating lymphocytes of typical and atypical medullary carcinomas of the breast[J]. Cancer Immun, 2010, 10:3.
45.	Rathore AS, Kumar S, Konwar R, et al. Presence of CD3⁺ tumor infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast[J]. IndianJ Cancer, 2013, 50(3):239-244.
46.	Loi S, Sirtaine N, Piette F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase Ⅲ randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy:BIG 02-98[J]. J Clin Oncol, 2013, 31(7):860-867.
47.	Dieci MV, Criscitiello C, Goubar A, et al. Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer:a retrospective multicenter study[J]. Ann Oncol, 2014, 25(3):611-618.
48.	Ma C, Zhang Q, Ye J, et al. Tumor-infiltrating γδ T lymphocytes predict clinical outcome in human breast cancer[J]. J Immunol, 2012, 189(10):5029-5036.
49.	Ladoire S, Martin F, Ghiringhelli F. Prognostic role of FOXP3⁺ regulatory T cells infiltrating human carcinomas:the paradox of colorectal cancer[J]. Cancer Immunol Immunother, 2011, 60(7):909-918.
50.	West NR, Kost SE, Martin SD, et al. Tumour-infiltrating FOXP3(+) lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer[J]. Br J Cancer, 2013, 108(1):155-162.
51.	Liu F, Li Y, Ren M, et al. Peritumoral FOXP3 regulatory T cell is sensitive to chemotherapy while intratumoral FOXP3 regulatory T cell is prognostic predictor of breast cancer patients[J]. Breast Cancer Res Treat, 2012, 135(2):459-467.
52.	Gobert M, Treilleux I, Bendriss-Vermare N, et al. Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome[J]. Cancer Res, 2009, 69(5):2000-2009.
53.	Ladoire S, Mignot G, Dalban C, et al. FOXP3 expression in cancer cells and anthracyclines efficacy in patients with primary breast cancer treated with adjuvant chemotherapy in the phaseⅢ UNICANCER-PACS 01 trial[J]. Ann Oncol, 2012, 23(10):2552-2561.
54.	Ladoire S, Arnould L, Mignot G, et al. Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy[J]. Breast Cancer Res Treat, 2011, 125(1):65-72.

1. Desantis C, Ma JM, Bryan L, et al. Breast cancer statistics, 2013[J]. CA Cancer J Clin, 2014, 64(1):52-62.
2. Pernas Simon S. Neoadjuvant therapy of early stage human epidermal growth factor receptor 2 positive breast cancer:latest evidence and clinical implications[J]. Ther Adv Med Oncol, 2014, 6(5):210-221.
3. Rampurwala MM, Rocque GB, Burkard ME. Update on adjuvant chemotherapy for early breast cancer[J]. Breast Cancer (Auckl), 2014, 8:125-133.
4. Bhattacharyya T, Sharma SC, Yadav BS, et al. Outcome of neoadjuvant chemotherapy in locally advanced breast cancer:atertiary care centre experience[J]. Indian J Med Paediatr Oncol, 2014, 35(3):215-220.
5. Li Q, Liu M, Ma F, et al. Circulating miR-19a and miR-205 in serum May predict the sensitivity of luminal A subtype of breast cancer patients to neoadjuvant chemotherapy with epirubicin plus paclitaxel[J]. PLoS One, 2014, 9(8):e104870.
6. Wang K, Deng QT, Liao N, et al. Tau expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy[J]. Tumour Biol, 2013, 34(1):33-38.
7. Yu KD, Liu GY, Zhou XY, et al. Association of HER-2 copy number and HER-2/CEP-17 ratio with neoadjuvant taxane-containing chemotherapy sensitivity in locally advanced breast cancer[J]. Oncologist, 2012, 17(6):792-800.
8. Tokuda E, Seino Y, Arakawa A, et al. Estrogen receptor-α directly regulates sensitivity to paclitaxel in neoadjuvant chemotherapy for breast cancer[J]. Breast Cancer Res Treat, 2012, 133(2):427-436.
9. Kaufmann M, Hortobagyi GN, Goldhirsch A, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer:an update[J]. J Clin Oncol, 2006, 24(12):1940-1949.
10. Jones RL, Smith IE. Neoadjuvant treatment for early-stage breast cancer:opportunities to assess tumour response[J]. Lancet Oncol, 2006, 7(10):869-874.
11. Smith IC, Heys SD, Hutcheon AW, et al. Neoadjuvant chemotherapy in breast cancer:significantly enhanced response with docetaxel[J]. J Clin Oncol, 2002, 20(6):1456-1466.
12. Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer[J]. J Clin Oncol, 1998, 16(8):2672-2685.
13. Lindner JL, Loibl S, Denkert C, et al. Expression of secreted protein acidic and rich in cysteine (SPARC) in breast cancer and response to neoadjuvant chemotherapy[J]. Ann Oncol, 2015, 26(1):95-100.
14. Chavez-Macgregor M, Brown E, Lei X, et al. Bisphosphonates and pathologic complete response to taxane-and anthracycline-based neoadjuvant chemotherapy in patients with breast cancer[J]. Cancer, 2012, 118(2):326-332.
15. Nahleh Z. Neoadjuvant chemotherapy for "triple negative" breast cancer:a review of current practice and future outlook[J]. Med Oncol, 2010, 27(2):531-539.
16. Chavez-Macgregor M, Litton J, Chen H, et al. Pathologic complete response in breast cancer patients receiving anthracycline-and taxane-based neoadjuvant chemotherapy:evaluating the effect of race/ethnicity[J]. Cancer, 2010, 116(17):4168-4177.
17. Townsend KN, Spowart JE, Huwait H, et al. Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma[J]. PLoS One, 2013, 8(12):e82406.
18. Preston CC, Maurer MJ, Oberg AL, et al. The ratios of CD8⁺ T cells to CD4⁺ CD25⁺ FOXP3⁺ and FOXP3^- T cells correlate with poor clinical outcome in human serous ovarian cancer[J]. PLoS One, 2013, 8(11):e80063.
19. Jung IK, Kim SS, Suh DS, et al. Tumor-infiltration of T-lymphocytes is inversely correlated with clinicopathologic factors in endometrial adenocarcinoma[J]. Obstet Gynecol Sci, 2014, 57(4):266-273.
20. Yamagami W, Susumu N, Tanaka H, et al. Immunofluorescence-detected infiltration of CD4⁺FOXP3⁺ regulatory T cells is relevant to the prognosis of patients with endometrial cancer[J]. Int J Gynecol Cancer, 2011, 21(9):1628-1634.
21. 翟志伟, 王振军. 肿瘤浸润淋巴细胞在结直肠癌中的研究进展[J]. 中华胃肠外科杂志, 2013, 16(8):797-800.
22. Zhang J, Huang SH, Li H, et al. Preoperative lymphocyte count is a favorable prognostic factor of disease-free survival in non-small-cell lung cancer[J]. Med Oncol, 2013, 30(1):352.
23. Issa-Nummer Y, Loibl S, Von Minckwitz G, et al. Tumor-infiltrating lymphocytes in breast cancer:a new predictor for responses to therapy[J]. Oncoimmunology, 2014, 3:e27926.
24. 徐林, 周涯, 肖代敏, 等. 乳腺癌患者CD4⁺ CD25 high CCR6⁺调节性T细胞的变化[J]. 四川大学学报:医学版, 2010, 41(3):415-419.
25. Mohammed ZM, Going JJ, Edwards J, et al. The relationship between components of tumour inflammatory cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer[J]. Br J Cancer, 2012, 107(5):864-873.
26. Hornychova H, Melichar B, Tomsova M, et al. Tumor-infiltrating lymphocytes predict response to neoadjuvant chemotherapy in patients with breast carcinoma[J]. Cancer Invest, 2008, 26(10):1024-1031.
27. Topalian SL, Solomon D, Rosenberg SA. Tumor-specific cytolysis by lymphocytes infiltrating human melanomas[J]. J Immunol, 1989, 142(10):3714-3725.
28. Baxevanis CN, Dedoussis GV, Papadopoulos NG, et al. Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer[J]. Cancer, 1994, 74(4):1275-1282.
29. Gu-Trantien C, Loi S, Garaud S, et al. CD4☒ follicular helper T cell infiltration predicts breast cancer survival[J]. J Clin Invest, 2013, 123(7):2873-2892.
30. Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes-dealing with the diversity of breast cancer:highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011[J]. Ann Oncol, 2011, 22(8):1736-1747.
31. Lee HJ, Seo JY, Ahn JH, et al. Tumor-associated lymphocytes predict response to neoadjuvant chemotherapy in breast cancer patients[J]. J Breast Cancer, 2013, 16(1):32-39.
32. Seo AN, Lee HJ, Kim EJ, et al. Tumour-infiltrating CD8⁺ lymphocytes as an Independent predictive factor for pathological complete response to primary systemic therapy in breast cancer[J]. Br J Cancer, 2013, 109(10):2705-2713.
33. Dong DD, Yie SM, Li K, et al. Importance of HLA-G expression and tumor infiltrating lymphocytes in molecular subtypes of breast cancer[J]. Hum Immunol, 2012, 73(10):998-1004.
34. Denkert C, Loibl S, Noske A, et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer[J]. J Clin Oncol, 2010, 28(1):105-113.
35. West NR, Milne K, Truong PT, et al. Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer[J]. Breast Cancer Res, 2011, 13(6):R126.
36. Ono M, Tsuda H, Shimizu C, et al. Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer[J]. Breast Cancer Res Treat, 2012, 132(3):793-805.
37. Melichar B, Hornychová H, Kalábová H, et al. Increased efficacy of a dose-dense regimen of neoadjuvant chemotherapy in breast carcinoma:a retrospective analysis[J]. Med Oncol, 2012, 29(4):2577-2585.
38. Apetoh L, Ghiringhelli F, Tesniere AA, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy[J]. Nat Med, 2007, 13(9):1050-1059.
39. Bellati F, Napoletano C, Gasparri ML, et al. Immunologic systemic effect of neoadjuvant chemotherapy requires investigation before tumor-associated lymphocytes can be introduced in breast cancer treatment algorithm[J]. J Clin Oncol, 2010, 28(27):e471-e472; author reply e473.
40. Ladoire S, Arnould L, Apetoh L, et al. Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating foxp3⁺ regulatory T cells[J]. Clin Cancer Res, 2008, 14(8):2413-2420.
41. Demir L, Yigit S, Ellidokuz H, et al. Predictive and prognostic factors in locally advanced breast cancer:effect of intratumoral FOXP3⁺ Tregs[J]. Clin Exp Metastasis, 2013, 30(8):1047-1062.
42. Mahmoud SM, Paish EC, Powe DG, et al. Tumor-infiltrating CD8⁺ lymphocytes predict clinical outcome in breast cancer[J]. J Clin Oncol, 2011, 29(15):1949-1955.
43. Liu S, Lachapelle J, Leung S, et al. CD8⁺ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer[J]. Breast Cancer Res, 2012, 14(2):R48.
44. Lim KH, Telisinghe PU, Abdullah MS, et al. Possible significance of differences in proportions of cytotoxic T cells and B-lineage cells in the tumour-infiltrating lymphocytes of typical and atypical medullary carcinomas of the breast[J]. Cancer Immun, 2010, 10:3.
45. Rathore AS, Kumar S, Konwar R, et al. Presence of CD3⁺ tumor infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast[J]. IndianJ Cancer, 2013, 50(3):239-244.
46. Loi S, Sirtaine N, Piette F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase Ⅲ randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy:BIG 02-98[J]. J Clin Oncol, 2013, 31(7):860-867.
47. Dieci MV, Criscitiello C, Goubar A, et al. Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer:a retrospective multicenter study[J]. Ann Oncol, 2014, 25(3):611-618.
48. Ma C, Zhang Q, Ye J, et al. Tumor-infiltrating γδ T lymphocytes predict clinical outcome in human breast cancer[J]. J Immunol, 2012, 189(10):5029-5036.
49. Ladoire S, Martin F, Ghiringhelli F. Prognostic role of FOXP3⁺ regulatory T cells infiltrating human carcinomas:the paradox of colorectal cancer[J]. Cancer Immunol Immunother, 2011, 60(7):909-918.
50. West NR, Kost SE, Martin SD, et al. Tumour-infiltrating FOXP3(+) lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer[J]. Br J Cancer, 2013, 108(1):155-162.
51. Liu F, Li Y, Ren M, et al. Peritumoral FOXP3 regulatory T cell is sensitive to chemotherapy while intratumoral FOXP3 regulatory T cell is prognostic predictor of breast cancer patients[J]. Breast Cancer Res Treat, 2012, 135(2):459-467.
52. Gobert M, Treilleux I, Bendriss-Vermare N, et al. Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome[J]. Cancer Res, 2009, 69(5):2000-2009.
53. Ladoire S, Mignot G, Dalban C, et al. FOXP3 expression in cancer cells and anthracyclines efficacy in patients with primary breast cancer treated with adjuvant chemotherapy in the phaseⅢ UNICANCER-PACS 01 trial[J]. Ann Oncol, 2012, 23(10):2552-2561.
54. Ladoire S, Arnould L, Mignot G, et al. Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy[J]. Breast Cancer Res Treat, 2011, 125(1):65-72.

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乳腺癌浸润淋巴细胞对新辅助化学疗法反应的预测及与预后的关系

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