肿瘤浸润淋巴细胞预测乳腺癌新辅助化疗疗效

doi:10.3969/j.issn.1009-976X.2024.02.003

摘要/Abstract

摘要： 目的利用苏木素和伊红（H＆E）染色评估肿瘤浸润淋巴细胞（TILs）浸润水平,探索TILs与乳腺癌新辅助化疗（NAC）疗效的相关性。方法收集87例乳腺浸润性导管癌术前经空芯针穿刺获得的组织样本,对组织样本行H＆E染色,显微镜下评估H＆E切片的TILs浸润情况,分析TILs水平与各临床病理特征的相关性及与新辅助化疗疗效的相关性。结果新辅助化疗前经空芯针穿刺标本中的TILs水平与乳腺癌分子分型密切相关,在HER2过表达及TNBC亚型中表达最高,TILs与激素受体ER、PR表达及NAC后病理完全缓解（pCR）显著相关,ER-、PR-患者中TILs水平更高（P<0.05）,高TILs浸润患者NAC后pCR率显著高于低TILs浸润患者（P<0.05）,同时,ER-、PR-患者pCR率更高（P<0.05）,logistic回归分析显示TILs是新辅助化疗疗效的独立预测因素（P=0.048）。结论 TILs是新辅助化疗疗效的独立预测因子,高TILs表达预示着新辅助化疗疗效更好,更容易达到pCR。

关键词: 乳腺癌, 新辅助化疗, 肿瘤浸润淋巴细胞

Abstract: Objective To evaluate the infiltration level of tumor infiltrating lymphocytes （TILs） and explore the correlation between TILs and the efficacy of neoadjuvant chemotherapy for breast cancer. Methods A total of 87 cases were included with invasive breast cancer were diagnosed by preoperative biopsy. TILs infiltration evaluated by H＆E staining under microscope. The correlation between the expression levels of TILs and clinicopathological features as well as the efficacy of neoadjuvant chemotherapy was analyzed. Results The expressions of TILs in the preoperative core needle biopsy were closely related to the molecular subtypes of breast cancer, and the expression was highest in the HER2 over-expression and triple negative breast cancer subtypes. TILs level was significantly correlated with the expression of ER, PR and pathological complete response（pCR）. TILs level was higher in ER-and PR- patients （P<0.05）. The pCR rate in patients with high TILs infiltration was significantly higher than that in low TILs infiltration （P<0.05）. The pCR rates were also higher in ER- and PR- patients （P<0.05）. Multivariate analysis showed that TILs was an independent predictor for efficacy of neoadjuvant chemotherapy （P=0.041）. Conclusion Our study found that TILs was an independent predictor of the efficacy of neoadjuvant chemotherapy. A high TILs lever indicates better therapeutic effect.

Key words: breast cancer, neoadjuvant chemotherapy, tumor infiltrating lymphocytes

中图分类号:

R739.7

邬慧倩, 倪亨吏, 周爱君, 袁杭, 李建明. 肿瘤浸润淋巴细胞预测乳腺癌新辅助化疗疗效[J]. 岭南现代临床外科, 2024, 24(02): 100-105.

WU Hui-qian, NI Heng-li, ZHOU Ai-jun, YUAN Hang, LI Jian-ming. Tumor infiltrating lymphocytes predict the efficacy of neoadjuvant chemotherapy for breast cancer[J]. Lingnan Modern Clinics In Surgery, 2024, 24(02): 100-105.

参考文献

[1] Sung H, Ferlay J, Siegel RL, et al.Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2] Chen Y, Qi Y, Wang K.Neoadjuvant chemotherapy for breast cancer: an evaluation of its efficacy and research progress[J]. Front Oncol, 2023, 13: 1169010.
[3] Sparano JA.Neoadjuvant Systemic Therapy for Breast Cancer: Searching for More Effectively Curative Therapies[J]. JAMA Oncol, 2018, 4(3): 293-295.
[4] Ruano Pérez R, Rebollo Aguirre AC, García-Talavera San Miguel P, et al. Review of the role of the sentinel node biopsy in neoadjuvant chemotherapy in women with breast cancer and negative or positive axillary node at diagnosis[J]. Rev Esp Med Nucl Imagen Mol (Engl Ed), 2018, 37(1): 63-70.
[5] Cortazar P, Zhang L, Untch M, et al.Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis[J]. Lancet, 2014, 384(9938): 164-172.
[6] Gao G, Wang Z, Qu X, et al.Prognostic value of tumor-infiltrating lymphocytes in patients with triple-negative breast cancer: a systematic review and meta-analysis[J]. BMC Cancer, 2020, 20(1): 179.
[7] Salgado R, Denkert C, Demaria S, et al.The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014[J]. Ann Oncol, 2015, 26(2): 259-271.
[8] Stanton SE, Adams S, Disis ML.Variation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes: A Systematic Review[J]. JAMA Oncol, 2016, 2(10): 1354-1360.
[9] Bear HD, Anderson S, Brown A, 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]. J Clin Oncol, 2003, 21(22): 4165-4174.
[10] Asano Y, Kashiwagi S, Goto W, et al.Prediction of survival after neoadjuvant chemotherapy for breast cancer by evaluation of tumor-infiltrating lymphocytes and residual cancer burden[J]. BMC Cancer, 2017, 17(1): 888.
[11] 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.
[12] Houssami N, Macaskill P, Von Minckwitz G, et al.Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy[J]. Eur J Cancer, 2012, 48(18): 3342-3354.
[13] Haque W, Verma V, Hatch S, et al.Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy[J]. Breast Cancer Res Treat, 2018, 170(3): 559-567.
[14] Cortazar P, Geyer CE.Pathological complete response in neoadjuvant treatment of breast cancer[J]. Ann Surg Oncol, 2015, 22(5): 1441-1446.
[15] Mao Y, Qu Q, Zhang Y, et al.The value of tumor infiltrating lymphocytes (TILs) for predicting response to neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis[J]. PLoS One, 2014, 9(12): e115103.
[16] Hwang HW, Jung H, Hyeon J, et al.A nomogram to predict pathologic complete response (pCR) and the value of tumor-infiltrating lymphocytes (TILs) for prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer patients[J]. Breast Cancer Res Treat, 2019, 173(2): 255-266.
[17] Denkert C, Von Minckwitz G, Darb-Esfahani S, et al.Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy[J]. Lancet Oncol, 2018, 19(1): 40-50.