Value of peripheral inflammatory markers NLR, PLR and LMR in predicting the efficacy of neoadjuvant chemotherapy for breast cancer
-
摘要:
目的 探讨乳腺癌患者新辅助化疗(neoadjuvant chemotherapy, NAC)前外周血中性粒细胞与淋巴细胞比值(neutrophil to lymphocyte ratio, NLR)、血小板与淋巴细胞比值(platelet to lymphocyte ratio, PLR)及淋巴细胞与单核细胞比值(lymphocyte to monocyte ratio, LMR)在NAC疗效评估中的价值。 方法 回顾性研究2018年12月—2020年10月于中国科学技术大学附属第一医院确诊并接受NAC的102例乳腺癌患者的临床资料,以病理完全缓解(pathological complete response, pCR)作为NAC疗效的评判指标,并对化疗前NLR、PLR及LMR水平与pCR的相关性进行单因素和多因素分析。 结果 在102例乳腺癌患者中,有24例(23.53%)接受NAC后达到pCR。经过单因素和多因素分析,患者的年龄、肿瘤大小、临床分期、ER状态、PR状态、Her-2状态、分子分型以及Ki-67水平与NAC后是否达到pCR无明显相关性(均P>0.05)。Logistic回归分析显示,化疗前外周血NLR、PLR水平与是否达到pCR显著相关(均P<0.05),低NLR组的患者达到pCR率显著高于高NLR组(P=0.010,95%CI:0.145~0.768),低PLR组的患者达到pCR率显著高于高PLR组(P=0.014,95%CI:0.153~0.808);而LMR水平与是否达到pCR无明显相关性(P>0.05)。 结论 乳腺癌患者NAC前外周血NLR、PLR水平与NAC后是否达到pCR显著相关,对局部晚期乳腺癌NAC治疗有一定的指导价值。 -
关键词:
- 乳腺癌 /
- 新辅助化疗 /
- 病理完全缓解 /
- 中性粒细胞与淋巴细胞比值 /
- 血小板与淋巴细胞比值 /
- 淋巴细胞与单核细胞比值
Abstract:Objective To investigate the value of peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) in evaluating the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer. Methods The clinical data of 102 breast cancer patients who received NAC from December 2018 to October 2020 at the First Affiliated Hospital of the University of Science and Technology of China were retrospectively analysed, and pathological complete response (pCR) was used to evaluate the efficacy of NAC for breast cancer. We analysed the correlation between NLR, PLR and LMR before NAC and pCR using single-factor and multiple-factor analysis. Results Amongst 102 breast cancer patients, 24 (23.53%) reached pCR after receiving NAC. After univariate and multivariate analysis, no significant correlation was found between age, tumour size, clinical stage, ER status, PR status, HER-2 status, molecular typing and Ki-67 level and whether the patients achieved pCR after receiving NAC (all P>0.05). Logistic regression analysis revealed that the level of peripheral blood NLR and PLR before NAC was significantly correlated with pCR rate (all P < 0.05). The pCR-attainment rate in the low-NLR group was significantly higher than that in the high-NLR group (P=0.010, 95% CI: 0.145-0.768). The pCR-attainment rate in the low-PLR group was significantly higher than that in the high-PLR group (P=0.014, 95% CI: 0.153-0.808). However, no significant correlation was observed between peripheral blood LMR level and pCR-attainment rate (P>0.05). Conclusion The NLR and PLR levels in the peripheral blood of breast cancer patients before NAC are significantly correlated with the pCR rate after accepting NAC, which has certain reference value for guiding the treatment of locally advanced breast cancer with NAC. -
表 1 乳腺癌患者临床病理特征与新辅助化疗疗效的关系(例)
临床因素 例数 病理疗效评估 χ2值 P值 pCR non-pCR 年龄 0.229 0.632 <45岁 25 5 20 ≥45岁 77 19 58 肿瘤大小分期 0.592 0.442 T1+T2 70 18 52 T3+T4 32 6 26 临床分期 2.172 0.141 Ⅱ 59 17 42 Ⅲ 43 7 36 ER状态 0.472 0.492 阳性 53 11 42 阴性 49 13 36 PR状态 0.732 0.392 阳性 46 9 37 阴性 56 15 41 Her-2状态 0.194 0.659 阳性 55 12 43 阴性 47 12 35 分子分型 1.726 0.189 Lumina 59 12 47 Her-2过表达型 23 6 17 三阴性 20 6 14 Ki-67 5.296 0.021 <14% 12 6 6 ≥14% 90 18 72 表 2 外周血NLR、PLR指标与新辅助化疗疗效的相关性分析(例)
炎症指标 类别 病理疗效评估 χ2值 P值 pCR non-pCR NLR ≥1.97 7 46 6.533 0.011 <1.97 17 32 PLR ≥110.97 8 51 7.732 0.005 <110.97 16 27 表 3 影响乳腺癌新辅助化疗病理完全缓解的多因素分析
因素 B SE Wald χ2 P值 OR(95%CI) ER -0.181 0.555 0.106 0.744 0.834(0.281~2.476) PR 0.554 0.639 0.724 0.395 1.723(0.492~6.030) Her-2 -0.193 0.432 0.200 0.654 0.824(0.353~1.922) Ki-67 -0.070 0.654 2.682 0.102 0.343(0.095~1.235) NLR -1.096 0.425 6.655 0.010 0.334(0.145~0.768) PLR -1.046 0.678 6.056 0.014 0.351(0.153~0.808) -
[1] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. doi: 10.3322/caac.21492 [2] 杨辉, 江皓. 新辅助TAC化疗对早期乳腺癌患者疗效、细胞免疫功能和Ki-67的影响[J]. 中华全科医学, 2017, 15(4): 555-557, 671. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201704004.htm [3] 程阳, 田君, 姚学权, 等. 局部晚期乳腺癌TEC方案新辅助化疗的临床疗效分析[J]. 安徽医学, 2020, 41(9): 1022-1025. doi: 10.3969/j.issn.1000-0399.2020.09.009 [4] MOSES C, GARCIA-BLOJ B, HARVEY A R, et al. Hallmarks of cancer: The CRISPR generation[J]. Eur J Cancer, 2018, 93: 10-18. doi: 10.1016/j.ejca.2018.01.002 [5] STEFANIUK P, SZYMCZYK A, PODHORECKA M. The neutrophil to lymphocyte and lymphocyte to monocyte ratios as new prognostic factors in hematological malignancies-A narrative review[J]. Cancer Manag Res, 2020, 12: 2961-2977. doi: 10.2147/CMAR.S245928 [6] 薛国军, 张艳利, 杨光伦. 外周血NLR和PLR预测非luminal型乳腺癌新辅助化疗临床进展的应用[J]. 现代医药卫生, 2019, 35(17): 2629-2632. doi: 10.3969/j.issn.1009-5519.2019.17.011 [7] 袁茂林, 韩琼, 吴斌. 外周血淋巴细胞和单核细胞比值与乳腺癌新辅助化疗疗效关联性[J]. 中华肿瘤防治杂志, 2020, 27(4): 283-287. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL202004008.htm [8] BUYUKSIMSEK M, OGUL A, MIRILI C, et al. Inflammatory markers predicting pathological complete response in cases with breast cancer treated by neoadjuvant chemotherapy[J]. Eur J Breast Health, 2020, 16(4): 229-234. doi: 10.5152/ejbh.2020.5556 [9] DERKS M G M, VAN DE VELDE C J H. Neoadjuvant chemotherapy in breast cancer: More than just downsizing[J]. Lancet Oncol, 2018, 19(1): 2-3. doi: 10.1016/S1470-2045(17)30914-2 [10] BOUGHEY J C, BALLMAN K V, MCCALL L M, et al. Tumor biology and response to chemotherapy impact breast cancer-specific survival in node-positive breast cancer patients treated with neoadjuvant chemotherapy: Long-term follow-up from ACOSOG Z1071(Alliance)[J]. Ann Surg, 2017, 266(4): 667-676. doi: 10.1097/SLA.0000000000002373 [11] KLEIN J, TRAN W, WATKINS E, et al. Locally advanced breast cancer treated with neoadjuvant chemotherapy and adjuvant radiotherapy: A retrospective cohort analysis[J]. BMC Cancer, 2019, 19(1): 306. doi: 10.1186/s12885-019-5499-2 [12] ALDAWSARI H M, GORAIN B, ALHAKAMY N A, et al. Role of therapeutic agents on repolarisation of tumour-associated macrophage to halt lung cancer progression[J]. J Drug Target, 2020, 28(2): 166-175. doi: 10.1080/1061186X.2019.1648478 [13] 张美云, 李晓凤, 刘卓. 中性粒细胞与淋巴细胞比值在乳腺癌新辅助化疗中的意义[J]. 癌症进展, 2018, 16(11): 1408-1410. https://www.cnki.com.cn/Article/CJFDTOTAL-AZJZ201811023.htm [14] 曲幽, 杜闯, 李靖若. 血小板与淋巴细胞比率对乳腺癌患者新辅助化疗后病理完全缓解的预测价值[J]. 肿瘤基础与临床, 2019, 32(6): 505-510. doi: 10.3969/j.issn.1673-5412.2019.06.012 [15] 王浩峰, 王耀辉, 陆劲松. 乳腺癌反映炎症状态外周血细胞间比值研究进展[J]. 中华肿瘤防治杂志, 2019, 26(8): 598-602. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL201908018.htm [16] TAKEUCHI H, KAWANAKA H, FUKUYAMA S, et al. Comparison of the prognostic values of preoperative inflammation-based parameters in patients with breast cancer[J]. PLoS One, 2017, 12(5): e0177137. doi: 10.1371/journal.pone.0177137 [17] WARISS B R, DE SOUZA A K, DE AGUIAR S S, et al. Effectiveness of four inflammatory markers in predicting prognosis in 2374 women with breast cancer[J]. Maturitas, 2017, 101: 51-56. doi: 10.1016/j.maturitas.2017.04.015 [18] 高思铭. 中性粒细胞与淋巴细胞比值预测乳腺癌新辅助化疗疗效及预后的研究[D]. 济南: 山东大学, 2020. [19] OU Q, CHENG J, ZHANG L, et al. The prognostic value of pretreatment neutrophil-to-lymphocyte ratio in breast cancer: Deleterious or advantageous?[J]. Tumour Biol, 2017, 39(6): 1010428317706214. http://www.onacademic.com/detail/journal_1000039945705910_78cc.html [20] 彭阳. 外周血中炎症相关细胞比值对乳腺癌患者新辅助化疗疗效的预测作用[D]. 重庆: 重庆医科大学, 2018. [21] 郑帅, 毛艳, 贺薇, 等. 乳腺癌患者外周血炎症指标与新辅助化疗疗效的相关性分析[J]. 肿瘤药学, 2020, 10(1): 97-102. https://www.cnki.com.cn/Article/CJFDTOTAL-LIYX202001018.htm [22] 周洁, 马景玲, 蒋冬梅, 等. 肿瘤相关炎症指标对乳腺癌新辅助化疗疗效预测价值研究[J]. 中国煤炭工业医学杂志, 2020, 23(6): 626-631. https://www.cnki.com.cn/Article/CJFDTOTAL-ZMGY202006014.htm [23] 何洋, 赵伟鹏, 佟仲生. 新辅助化疗对乳腺癌ER、PR、HER-2及Ki-67表达影响的研究进展[J]. 中国肿瘤临床, 2020, 47(22): 1185-1188. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZL202022017.htm [24] ACS B, ZAMBO V, VIZKELETI L, et al. Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy[J]. Diagn Pathol, 2017, 12(1): 20. doi: 10.1186/s13000-017-0608-5 [25] 张彦收, 唐甜甜, 周涛, 等. Ki-67表达水平检测在乳腺癌新辅助化疗疗效评估中的价值[J]. 现代肿瘤医学, 2017, 25(14): 2256-2259. https://www.cnki.com.cn/Article/CJFDTOTAL-SXZL201714017.htm -