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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2023, Vol. 17 ›› Issue (04) : 210 -217. doi: 10.3877/cma.j.issn.1674-0807.2023.04.003

论著

进展期肺癌炎症指数对三阴性乳腺癌的预后价值和临床意义
高文伯†(), 李明, 张运昊   
  1. 154002　黑龙江佳木斯市中心医院肿瘤外1科
  • 收稿日期:2022-11-14 出版日期:2023-08-01
  • 通信作者: 高文伯

Prognostic value and clinical significance of advanced lung cancer inflammation index in patients with triple negative breast cancer

Wenbo Gao†(), Ming Li, Yunhao Zhang   

  1. Department of Oncology Surgery, Jiamusi Central Hospital, Jiamusi 154002, China
  • Received:2022-11-14 Published:2023-08-01
  • Corresponding author: Wenbo Gao
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引用本文：

高文伯, 李明, 张运昊. 进展期肺癌炎症指数对三阴性乳腺癌的预后价值和临床意义[J/OL]. 中华乳腺病杂志(电子版), 2023, 17(04): 210-217.

Wenbo Gao, Ming Li, Yunhao Zhang. Prognostic value and clinical significance of advanced lung cancer inflammation index in patients with triple negative breast cancer[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2023, 17(04): 210-217.

目的

探讨进展期肺癌炎症指数(ALI)对三阴性乳腺癌的预后价值和临床意义。

方法

回顾性分析2010年1月至2015年12月在黑龙江佳木斯市中心医院治疗的164例三阴性乳腺癌患者临床病理资料，应用受试者工作特征曲线(ROC)确定术前ALI最佳截断值。将所有患者分为低ALI组和高ALI 2组。计数资料的组间比较采用卡方检验，等级资料的组间比较采用非参数检验。采用Kaplan-Meier法绘制生存曲线，生存曲线的比较采用Log-rank检验。采用Cox比例风险回归模型进行多因素分析。

结果

术前ALI的曲线下面积(AUC)为0.657，根据最大约登指数计算出ALI最佳截断值为42.0，ALI≥42.0为高ALI组(n＝89)，ALI<42.0为低ALI组(n＝75)。术前低、高ALI 2组患者临床T分期、手术方式比较，差异具有统计学意义(Z＝－2.719，P＝0.007；χ2＝4.616，P＝0.032)。低、高ALI 2组患者在白细胞计数、中性粒细胞计数、淋巴细胞计数等方面比较，差异具有统计学意义(χ2＝16.128，P<0.001；χ2＝36.419，P<0.001；χ2＝6.501，P＝0.011)。高、低ALI组中位DFS分别为49.1个月和27.8个月，中位OS分别为73.4个月和52.7个月。低ALI组复发风险高于高ALI组(DFS：HR＝2.264，95%CI：1.309~3.918，P＝0.004；OS：HR＝2.017，95%CI：1.169~3.470，P＝0.012)。多因素分析显示，中性粒细胞计数≥3.74×109/L、肿瘤>2 cm、病理组织学类型为乳腺浸润性小叶癌、不接受辅助化疗、ALI<42.0是TNBC患者DFS和OS预后不良的影响因素；临床T分级≥T2和区域淋巴结阳性数≥4枚还是OS预后不良的影响因素。

结论

低ALI是TNBC患者的不良预后因素，ALI检测具有费用低廉、重复性强、安全性高等优点，可用于预测TNBC患者的临床预后。

关键词: 乳腺肿瘤, 炎性因子, 预后
Objective

To explore the potential prognostic value and clinical significance of advanced lung cancer inflammation index (ALI) in triple negative breast cancer (TNBC) patients.

Methods

The clinicopathological data of 164 patients with TNBC who were treated in Jiamusi Central Hospital from January 2010 to December 2015 were retrospectively analyzed. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of ALI in pre-operation. All patients were divided into low ALI group and high ALI group. The enumeration data were compared by chi-square test, while the non-parametric test was used for comparison of rank data between groups. Kaplan Meier method and log rank method were used for survival analysis. The Cox’s proportional hazards regression model was used for multivariate analysis.

Results

The area under the curve (AUC) of ALI was 0.657 in pre-operation. Based on the maximum value of Youden index, the optimal cutoff value for ALI was 42.0. The patients with ALI≥42.0 constituted high ALI group (n=89) and the patients with ALI<42.0 constituted low ALI group (n=75). There was a significant difference in clinical T stage, surgical methods, white blood cell count, neutrophil count, and lymphocyte count between high ALI group and low ALI group (Z=-2.719, P=0.007; χ2=4.616, P=0.032, χ2=16.128, P<0.001; χ2=36.419, P<0.001; χ2=6.501, P=0.011). In high ALI group, the median DFS and OS were 48.13 months and 73.4 months; in low ALI group, the median DFS and OS were 27.8 months and 52.7 months, respectively. The risk of recurrence was significantly higher in low ALI group than in high ALI group (DFS: HR=2.264, 95%CI: 1.309-3.918, P=0.004; OS: HR=2.017, 95%CI: 1.169-3.470, P=0.012). Multivariate analysis showed that neutrophil count≥3.74×109/L, tumor size>2 cm, histopathological type of invasive lobular carcinoma of the breast, lack of adjuvant chemotherapy, and ALI<42.0 were risk factors of DFS and OS in TNBC patients, while clinical T stage≥T2, no less than 4 positive regional lymph nodes were risk factors of OS in TNBC patients.

Conclusions

Low ALI indicates poor prognosis for TNBC patients. ALI is a promising biomarker to predict clinical prognosis of TNBC, with the advantages of low cost, strong repeatability, and high safety.

Key words: Triple negative breast neoplasms, Inflammatory factor, Prognosis
表1 Cox比例风险回归模型变量赋值情况
变量类型 变量类型 赋值
家族史 X1 否＝1；是＝2
中性粒细胞计数 X2 <3.74×109/L＝1；≥3.74×109/L＝2
肿瘤大小 X3 ≤2 cm＝1；>2 cm＝2
临床T分期 X4 T1期＝1；≥T2期＝2
肿瘤类型 X5 浸润性导管癌＝1；浸润性小叶癌＝2
淋巴结阳性数 X6 <4枚＝1；≥4枚＝2
辅助化疗 X7 否＝1；是＝2
ALI X8 <42.0＝1；≥42.0＝2
DFS Y1 疾病未进展＝0；疾病进展＝1
OS Y2 生存＝0；死亡＝1
图1 164例三阴性乳腺癌患者ALI与DFS关系的ROC曲线注：ALI为进展期肺癌炎症指数；DFS为无病生存期；ROC为受试者工作特征曲线
表2 低ALI组和高ALI组三阴性乳腺癌患者临床病理特征比较[例(%)]
临床病理特征 高ALI组(n＝89) 低ALI组(n＝75) 检验值 P值
婚姻情况        
已婚 83(93.3) 71(94.7) χ2＝0.002 0.962
未婚 6(6.7) 4(5.3)
职业        
脑力劳动者a 38(42.7) 38(50.7) χ2＝1.040 0.308
体力劳动者b 51(57.3) 37(49.3)
BMI        
<24.0 kg/m2 51(57.3) 47(62.7) χ2＝0.487 0.485
≥24.0 kg/m2 38(42.7) 28(37.3)
家族史        
否 68(41.5) 48(64.0) χ2＝3.025 0.082
是 21(58.5) 27(36.0)
ABO血型        
A型 19(21.3) 22(29.3) χ2＝4.858 0.302
B型 29(32.6) 31(41.3)
O型 30(33.7) 16(21.4)
AB型 11(12.4) 6(8.0)
肿瘤位置        
外上象限 58(65.2) 53(70.7) χ2＝3.195 0.526
外下象限 9(10.1) 8(10.7)
内下象限 2(2.2) 4(5.3)
内上象限 15(16.9) 8(10.7)
中央区 5(5.6) 2(2.6)
超声肿瘤大小        
≤2 cm 46(51.7) 29(38.7) χ2＝3.027 0.220
>2 cm且≤5 cm 38(42.7) 39(52.0)
>5 cm 5(5.6) 7(9.3)
区域淋巴结转移        
否 69(77.5) 56(74.7) χ2＝0.184 0.668
是 20(22.5) 19(25.3)
超声BI-RADS        
4类 16(18.0) 8(10.7) χ2＝2.304 0.316
5类 34(38.2) 27(36.0)
6类 39(43.8) 40(53.3)
年龄        
<47岁 40(44.9) 37(49.3) χ2＝0.315 0.575
≥47岁 49(55.1) 38(50.7)
绝经        
否 48(53.9) 49(55.1) χ2＝2.189 0.139
是 41(46.1) 26(44.9)
临床T分期        
T1期 28(31.5) 16(21.4) Z＝－2.719 0.007
T2期 49(55.1) 34(45.3)
T3期 10(11.2) 19(25.3)
T4期 2(2.2) 6(8.0)
临床N分期        
N0期 31(34.8) 28(37.3) Z＝－0.608 0.544
N1期 24(27.0) 22(29.3)
N2期 23(25.8) 18(24.0)
N3期 11(12.4) 7(9.4)
临床TNM分期        
Ⅰ期 13(14.6) 6(8.0) Z＝－0.444 0.657
Ⅱ期 39(43.8) 38(50.7)
Ⅲ期 37(41.6) 31(41.3)
手术方式        
改良根治术 62(69.7) 63(84.0) χ2＝4.616 0.032
保留乳房手术 27(30.3) 12(16.0)
病理肿瘤大小        
≤2 cm 49(55.1) 42(56.0) Z＝－0.347 0.729
>2 cm且≤5 cm 39(43.8) 26(34.7)
>5 cm 1(1.1) 7(9.3)
病理类型        
浸润性导管癌 85(95.5) 70(93.3) χ2＝0.370 0.543
浸润性小叶癌 4(4.5) 5(6.7)
组织学分级        
1级 14(15.7) 13(17.4) Z＝－1.140 0.254
2级 29(32.6) 31(41.3)
3级 46(51.7) 31(41.3)
病理T分期        
T1期 63(70.8) 46(61.3) Z＝－1.570 0.116
T2期 25(28.1) 22(29.3)
T3期 1(1.1) 5(6.7)
T4期 0(0.0) 2(2.7)
病理N分期        
N0期 43(48.3) 34(45.3) Z＝－1.238 0.216
N1期 25(28.1) 11(14.7)
N2期 10(11.2) 15(20.0)
N3期 11(12.4) 15(20.0)
病理TNM分期        
Ⅰ期 31(34.8) 27(36.0) Z＝－1.145 0.252
Ⅱ期 37(41.6) 18(24.0)
Ⅲ期 21(23.6) 30(40.0)
区域淋巴结清扫总数        
<21枚 50(56.2) 40(53.3) χ2＝0.133 0.715
≥21枚 39(43.8) 35(46.7)
区域淋巴结阳性数        
<4枚 69(77.5) 50(66.7) χ2＝2.412 0.120
≥4枚 20(22.5) 25(33.3)
脉管瘤栓        
否 71(79.8) 57(76.0) χ2＝0.339 0.561
是 18(20.2) 18(24.0)
神经侵袭        
否 82(92.1) 67(89.3) χ2＝0.384 0.535
是 7(7.9) 8(10.7)
术后并发症        
否 84(94.4) 67(89.3) χ2＝1.421 0.233
是 5(5.6) 8(10.7)
辅助化疗        
否 31(34.8) 23(30.7) χ2＝0.320 0.572
是 58(65.2) 52(69.3)
放射治疗        
否 25(28.1) 22(29.3) χ2＝0.031 0.861
是 64(71.9) 53(70.7)
表3 低ALI组和高ALI组三阴性乳腺癌患者外周血细胞计数的比较[例(%)]
外周血细胞计数 高ALI组(n＝89) 低ALI组(n＝75) χ2值 P值
白细胞计数        
<6.00×109/L 60(67.4) 27(36.0) 16.128 <0.001
≥6.00×109/L 29(32.6) 48(64.0)
红细胞计数        
<4.31×1012/L 39(43.8) 35(46.7) 0.133 0.715
≥4.31×1012/L 50(56.2) 40(53.3)
中性粒细胞计数        
<3.74×109/L 68(76.4) 22(29.3) 36.419 0.001
≥3.74×109/L 21(23.6) 53(70.7)
淋巴细胞计数        
<1.78×109/L 38(42.7) 47(62.7) 6.501 0.011
≥1.78×109/L 51(57.3) 28(37.3)
单核细胞计数        
<0.41×109/L 48(53.9) 46(61.3) 0.911 0.340
≥0.41×109/L 41(46.1) 29(38.7)
嗜酸性细胞计数        
<0.10×109/L 60(67.4) 59(78.7) 2.588 0.108
≥0.10×109/L 29(32.6) 16(21.3)
嗜碱性细胞计数        
<0.03×109/L 45(50.6) 46(61.3) 1.912 0.167
≥0.03×109/L 44(49.4) 29(38.7)
血小板计数        
<240.00×109/L 50(56.2) 38(50.7) 0.498 0.481
≥240.00×109/L 39(43.8) 37(49.3)
图2 高ALI组与低ALI组三阴性乳腺癌患者无瘤生存和总生存曲线比较　a图为无瘤生存曲线；b图为总生存曲线注：Log-rank检验，无瘤生存曲线：χ2＝8.529，P＝0.004；总生存曲线：χ2＝6.283，P＝0.012；ALI为进展期肺癌炎症指数
表4 影响164例三阴性乳腺癌患者DFS和OS的单因素分析
变量 DFS OS
P值 HR(95%CI) P值 HR(95%CI)
年龄        
<47岁   1.000   1.000
≥47岁 0.942 1.029(0.473~2.239) 0.527 0.769(0.341~1.736)
婚姻情况        
已婚   1.000   1.000
未婚 0.280 0.303(0.035~2.636) 0.241 0.236(0.021~2.637)
职业        
脑力劳动者   1.000   1.000
体力劳动者 0.610 0.847(0.449~1.600) 0.472 0.785(0.407~1.517)
BMI        
<24.00 kg/m2   1.000   1.000
≥24.00 kg/m2 0.212 0.659(0.343~1.269) 0.682 0.870(0.447~1.694)
家族史        
否   1.000   1.000
是 0.013 2.238(1.183~4.236) 0.054 1.937(0.990~3.789)
绝经情况        
否   1.000   1.000
是 0.491 0.739(0.312~1.748) 0.913 1.051(0.435~2.536)
白细胞计数        
<6.00×109/L   1.000   1.000
≥6.00×109/L 0.590 0.730(0.232~2.292) 0.292 0.523(0.156~1.748)
红细胞计数        
<4.31×1012/L   1.000   1.000
≥4.31×1012/L 0.210 0.607(0.277~1.327) 0.133 0.552(0.255~1.198)
血红蛋白        
<130.00 g/L   1.000   1.000
≥130.00 g/L 0.746 1.136(0.525~2.458) 0.540 1.283(0.578~2.850)
中性粒细胞计数        
<3.74×109/L   1.000   1.000
≥3.74×109/L 0.015 1.314(1.027~3.974) 0.021 1.965(1.008~6.354)
淋巴细胞计数        
<1.78×109/L   1.000   1.000
≥1.78×109/L 0.100 0.567(0.288~1.114) 0.072 0.513(0.248~1.061)
单核细胞计数        
<0.41×109/L   1.000   1.000
≥0.41×109/L 0.458 1.296(0.653~2.570) 0.865 0.941(0.466~1.899)
嗜酸性细胞计数        
<0.10×109/L   1.000   1.000
≥0.10×109/L 0.892 0.957(0.503~1.820) 0.046 2.026(1.014~4.049)
嗜碱性细胞计数        
<0.03×109/L   1.000   1.000
≥0.03×109/L 0.242 1.460(0.774~2.756) 0.074 1.908(0.940~3.874)
血小板计数        
<240.00×109/L   1.000   1.000
≥240.00×109/L 0.448 1.296(0.664~2.530) 0.292 1.447(0.728~2.879)
肿瘤位置        
外上象限   1.000   1.000
其他位置 0.247 1.543(0.740~3.218) 0.583 1.226(0.593~2.537)
超声肿瘤大小        
≤2 cm   1.000   1.000
>2 cm 0.739 1.357(0.401~3.912) 0.680 1.847(0.385~4.865)
超声淋巴结转移        
否   1.000   1.000
是 0.108 2.065(0.853~4.996) 0.134 1.998(0.808~4.942)
超声BI-RADS        
4、5类   1.000   1.000
6类 0.592 1.830(0.421~4.639) 0.278 1.664(0.317~3.391)
临床T分期        
T1期   1.000   1.000
≥T2期 0.094 2.205(0.874~5.563) 0.025 2.947(1.147~7.574)
临床N分期        
N0期   1.000   1.000
≥N1期 0.233 1.609(0.270~4.374) 0.354 1.666(0.282~3.573)
临床TNM分期        
Ⅰ、Ⅱ期   1.000   1.000
Ⅲ期 0.344 2.677(0.302~5.518) 0.317 1.644(0.271~4.526)
手术方式        
改良根治术   1.000   1.000
保留乳房手术 0.294 0.626(0.261~1.501) 0.747 0.866(0.360~2.079)
病理肿瘤大小        
≤2 cm   1.000   1.000
>2 cm 0.006 1.911(1.225~4.191) 0.037 2.514(1.058~5.972)
肿瘤类型        
浸润性导管癌   1.000   1.000
浸润性小叶癌 0.013 3.835(1.333~11.031) 0.025 3.879(1.189~12.652)
组织学分级        
1、2级   1.000   1.000
3级 0.998 0.999(0.573~1.742) 0.056 1.827(0.967~4.339)
病理T分期        
T1期   1.000   1.000
≥T2期 0.305 2.662(0.301~6.455) 0.132 1.533(0.235~8.208)
病理N分期        
N0期   1.000   1.000
≥N1期 0.169 1.931(0.756~4.930) 0.559 1.364(0.482~3.854)
病理TNM分期        
Ⅰ、Ⅱ期   1.000   1.000
Ⅲ期 0.747 1.778(0.170~4.564) 0.803 1.811(0.156~4.207)
清扫区域淋巴结数        
<21枚   1.000   1.000
≥21枚 0.351 1.708(0.343~3.461) 0.093 2.525(0.948~6.114)
区域淋巴结阳性数        
<4枚   1.000   1.000
≥4枚 0.280 2.132(0.539~8.424) 0.025 4.329(1.202~15.596)
术后并发症        
否   1.000   1.000
是 0.386 1.585(0.559~4.494) 0.218 1.869(0.692~5.047)
辅助化疗        
否   1.000   1.000
是 0.001 5.242(2.003~13.714) 0.008 3.928(1.426~10.817)
术后放射治疗        
否   1.000   1.000
是 0.671 0.849(0.399~1.808) 0.949 1.028(0.435~2.433)
脉管瘤栓        
否   1.000   1.000
是 0.975 0.987(0.443~2.200) 0.362 1.437(0.659~3.135)
神经侵袭        
否   1.000   1.000
是 0.432 0.680(0.260~1.780) 0.262 1.577(0.320~4.508)
ALI        
<42.0   1.000   1.000
≥42.0 0.026 1.705(1.067~2.725) 0.022 1.728(1.084~2.756)
表5 影响164例三阴性乳腺癌患者DFS和OS的多因素分析
参数 DFS OS
P值 HR(95%CI) P值 HR(95%CI)
中性粒细胞计数        
<3.74×109/L   1.000   1.000
≥3.74×109/L 0.034 3.191(1.701~14.537) 0.033 2.090(1.901~8.569)
临床T分期        
T1期       1.000
≥T2期     0.013 2.279(1.679~7.651)
病理肿瘤大小        
≤2 cm   1.000   1.000
>2 cm 0.009 2.199(1.275~6.406) 0.034 3.368(1.099~10.322)
肿瘤类型        
浸润性导管癌   1.000   1.000
浸润性小叶癌 0.027 3.494(1.872~13.990) 0.028 3.631(1.867~15.201)
区域淋巴结阳性数        
<4枚       1.000
≥4枚     <0.001 3.945(2.026~7.683)
辅助化疗        
否   1.000   1.000
是 0.019 3.429(1.222~9.625) 0.034 2.240(1.061~4.729)
ALI        
<42.0   1.000   1.000
≥42.0 0.008 2.251(1.233~4.110) 0.002 2.560(1.423~4.605)
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