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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 (06) : 353 -361. doi: 10.3877/cma.j.issn.1674-0807.2023.06.005

论著

腋窝淋巴结阳性Luminal A型乳腺癌患者新辅助与辅助化疗的预后及影响因素分析
施杰, 李云涛, 高海燕†()   
  1. 213000　江苏省常州市肿瘤医院乳腺外科
    050035　石家庄，河北医科大学第四医院乳腺中心
  • 收稿日期:2023-01-16 出版日期:2023-12-01
  • 通信作者: 高海燕
  • 基金资助:
    常州市卫健委重大科技资助项目(ZD202225)

Prognosis of node-positive luminal A breast cancer patients with neoadjuvant and adjuvant chemotherapy and influencing factors

Jie Shi, Yuntao Li, Haiyan Gao†()   

  1. Department of Breast Surgery, Changzhou Cancer Hospital, Changzhou 213000, China
    Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China
  • Received:2023-01-16 Published:2023-12-01
  • Corresponding author: Haiyan Gao
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引用本文：

施杰, 李云涛, 高海燕. 腋窝淋巴结阳性Luminal A型乳腺癌患者新辅助与辅助化疗的预后及影响因素分析[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 353-361.

Jie Shi, Yuntao Li, Haiyan Gao. Prognosis of node-positive luminal A breast cancer patients with neoadjuvant and adjuvant chemotherapy and influencing factors[J]. Chinese Journal of Breast Disease(Electronic Edition), 2023, 17(06): 353-361.

目的

比较腋窝淋巴结阳性Luminal A型乳腺癌患者接受新辅助化疗和辅助化疗的预后差异。

方法

回顾性分析美国国立癌症研究所监测、流行病学和最终结果(SEER)数据库(8.4.0.1)数据库中2010年1月1日至2012年12月31日登记的具有完整随访资料的13 447例腋窝淋巴结阳性Luminal A型乳腺癌患者资料，其中新辅助化疗组(NAC)1 534例，辅助化疗组(AC)11 913例。采用1∶1近邻匹配法行倾向评分匹配法(PSM)平衡混杂因素，共匹配到2 974例腋窝淋巴结阳性Luminal A型乳腺癌患者，其中NAC组和AC组各1 487例。采用Kaplan-Meier法绘制生存曲线，Log-rank检验比较生存曲线。采用Cox比例风险回归模型进行预后影响因素分析。

结果

PSM前2组患者在诊断年龄、肿瘤分期、T分期、N分期、组织学分级、种族、婚姻状况和病理类型方面的差异均具有统计学意义(Z＝－8.877、－19.168、－28.034、－5.807、－9.575、χ2＝18.205、14.460、4.600, P均<0.050)，PSM后NAC组和AC组患者的临床病理特征比较，差异均无统计学意义(P均>0.050)。NAC组和AC组的5年OS率分别为78.9%和86.5%，生存分析显示AC组患者预后优于NAC组患者(χ2＝34.575, P<0.001)。亚组分析显示2组患者中N分期越晚，预后越差(NAC组：χ2＝96.422, P<0.001; AC组：χ2＝47.205, P<0.001)。不同N分期组中AC组预后均优于NAC组患者(N1期：χ2＝11.585, P＝0.001; N2期：χ2＝13.060, P<0.001; N3期：χ2＝12.245, P<0.001)。在N2期中接受放射治疗的患者预后优于未接受放射治疗的患者(χ2＝12.426, P<0.001)。多因素Cox比例风险回归模型分析显示相比新辅助化疗，辅助化疗能够改善患者预后(HR＝0.613, 95%CI: 0.523~0.719, P<0.001)，同时诊断年龄、种族、T分期、N分期、组织学分级均是患者的独立预后因素(>60岁比<45岁：HR＝1.438, 95%CI: 1.158~1.785, P＝0.001;黑种人比白种人：HR＝1.323, 95%CI: 1.076~1.627, P＝0.008;其他种族比白种人：HR＝0.474, 95%CI: 0.339~0.664, P<0.001; T1比T0: HR＝0.111, 95%CI: 0.034~0.360, P<0.001; T2比T0: HR＝0.183, 95%CI: 0.058~0.576, P＝0.004; N3比N1: HR＝2.007, 95%CI: 1.582~2.547, P<0.001; 3级比1级：HR＝2.296, 95%CI: 1.640~3.215, P<0.001)。

结论

腋窝淋巴结阳性Luminal A型乳腺癌患者辅助化疗优于新辅助化疗，但应考虑患者的复发风险因素，综合制定个体化治疗方案。

关键词: 乳腺肿瘤, 辅助化疗, 预后
Objective

To compare the prognosis between neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) in patients with node-positive luminal A breast cancer.

Methods

The clinical data of 13 447 node-positive luminal A breast cancer patients with complete follow-up results in the Surveillance, Epidemiology, and Results (SEER) database (8.4.0.1) from January 1, 2010 to December 31, 2012 were retrospectively analyzed, including 1 534 patients in the NAC group and 11 913 patients in the AC group. A total of 2 974 patients with node-positive luminal A breast cancer were obtained by the propensity score matching (1∶1 nearest neighbor matching) to balance confounding factors, including 1 487 patients in the NAC group and 1487 patients in the AC group. The Kaplan-Meier method was used to draw survival curves, and the log-rank test was used for comparison. The Cox proportional risk regression model was used to analyze the prognostic factors.

Results

There were significant differences in age at diagnosis, tumor stage, T stage, N stage, histological grade, race, marital status and pathological type between two groups before PSM (Z=-8.877, -19.168, -28.034, -5.807, -9.575, χ2=18.205, 14.460, 4.600; all P<0.050), while no significant difference was found in clinicopathological characteristics between the NAC group and the AC group after PSM (all P >0.050). The 5-year OS was 78.9% and 86.5% in the NAC and AC group, respectively. Survival analysis showed that the patients in the AC group had a significantly better prognosis compared with the NAC group (χ2=34.575, P<0.001). Subgroup analysis showed that the later the N stage, the poorer the prognosis in both groups (NAC group: χ2=96.422, P<0.001; AC group: χ2=47.205, P<0.001). In the patients with different N stage, the prognosis of the AC group was significantly better than that of the NAC group (N1: χ2=11.585, P=0.001; N2: χ2=13.060, P<0.001; N3: χ2=12.245, P<0.001). In the patients at N2stage, the patients who received radiation therapy had a significantly better prognosis than those who did not receive radiation therapy (χ2=12.426, P<0.001). Multivariate Cox proportional risk regression model analysis showed that AC improved the prognosis better than NAC did (HR=0.613, 95%CI: 0.523-0.719, P<0.001); the age at diagnosis, race, T stage, N stage and histological grade were all independent prognostic factors (>60 years vs <45 years: HR=1.438, 95%CI: 1.158-1.785, P=0.001; black vs white: HR=1.323, 95%CI: 1.076-1.627, P=0.008; other races vs white people: HR=0.474, 95%CI: 0.339-0.664, P<0.001; T1 vs T0: HR=0.111, 95%CI: 0.034-0.360, P<0.001; T2 vs T0: HR=0.183, 95%CI: 0.058-0.576, P=0.004; N3 vs N1: HR=2.007, 95%CI: 1.582-2.547, P<0.001; G3 vs G1: HR=2.296, 95%CI: 1.640-3.215, P<0.001).

Conclusion

The efficacy of AC is better than NAC in patients with node-positive luminal A breast cancer; however, the clinicians should make individualized treatment plans considering the risk factors of recurrence.

Key words: Breast neoplasms, Chemotherapy, Adjuvant, Prognosis
表1 腋窝淋巴结阳性Luminal A型乳腺癌患者总生存的Cox比例风险回归分析变量赋值表
变量 变量类型 赋值
类型 X1 新辅助化疗＝0；辅助化疗＝1
年龄 X2 <45岁＝0；45~60岁＝1；>60岁＝2
种族 X3 白种人＝0；黑种人＝1；其他＝2
婚姻状况 X4 已婚＝1；其他＝2
病理类型 X5 浸润性导管癌＝0；其他＝1
原发灶位置 X6 左侧＝1；右侧＝2
肿瘤分期 X7 I期＝1；II期＝2；III期＝3
T分期 X8 T0＝0；T1＝1；T2＝2；T3＝3；T4＝4
N分期 X9 N1＝1；N2＝2；N3＝3
组织学分级 X10 1级＝1；2级＝2；3级＝3；4级＝4
放射治疗 X11 无＝0；有＝1
生存结局 Y 生存＝0；死亡＝1
表2 腋窝淋巴结阳性Luminal A型乳腺癌新辅助化疗和辅助化疗2组患者PSM前后基线特征比较[例(%)]
临床病理特征 PSM前(n＝13 447) PSM后(n＝2 974)
新辅助化疗(n＝1 534) 辅助化疗(n＝11 913) 检验值 P值 新辅助化疗(n＝1 487) 辅助化疗(n＝1 487) 检验值 P值
年龄                
<45岁 447(29.1) 2 115(17.8) Z＝－8.877 <0.001 428(28.8) 365(24.5) Z＝－1.077 0.281
45~60岁 655(42.7) 5 663(47.5) 636(42.8) 718(48.3)
>60岁 432(28.2) 4 135(34.7) 423(28.4) 404(27.2)
诊断时间                
2010年 514(33.5) 3 934(33.0) χ2＝0.728 0.695 496(33.3) 467(31.4) χ2＝1.979 0.372
2011年 526(34.3) 4 013(33.7) 508(34.2) 504(33.9)
2012年 494(32.2) 3 966(33.3) 483(32.5) 516(34.7)
种族                
白种人 1 156(75.4) 9 419(79.1) χ2＝18.205 <0.001 1 126(75.7) 1 130(76.0) χ2＝1.812 0.404
黑种人 221(14.4) 1 286(10.8) 211(14.2) 191(12.8)
其他 157(10.2) 1 208(10.1) 150(10.1) 166(11.2)
婚姻状况                
已婚 856(55.8) 7 249(60.8) χ2＝14.460 <0.001 837(56.3) 853(57.4) χ2＝0.351 0.554
其他 678(44.2) 4 664(39.2) 650(43.7) 634(42.6)
病理类型                
浸润性导管癌 1 140(74.3) 8 542(71.7) χ2＝4.600 0.032 1 100(74.0) 1 105(74.3) χ2＝0.044 0.834
其他 394(25.7) 3 371(28.3) 387(26.0) 382(25.7)
原发灶位置                
左侧 756(49.3) 5 894(49.5) χ2＝0.020 0.887 738(49.6) 731(49.2) χ2＝0.066 0.797
右侧 778(50.7) 6 019(50.5) 749(50.4) 756(50.8)
肿瘤分期                
Ⅰ期 16(1.0) 854(7.2)     16(1.1) 40(2.7)    
Ⅱ期 601(39.2) 6 823(57.3) Z＝－19.168 <0.001 601(40.4) 578(38.9) Z＝－0.405 0.686
Ⅲ期 917(59.8) 4 236(35.6) 870(58.5) 869(58.4)
T分期                
T0 4(0.3) 12(0.1) Z＝－28.034 <0.001 4(0.3) 0 Z＝－0.799 0.424
T1 218(14.2) 4 646(39.0) 218(14.7) 256(17.2)
T2 670(43.7) 5 709(47.9) 670(45.0) 619(41.6)
T3 380(24.8) 1 315(11.0) 376(25.3) 433(29.1)
T4 262(17.1) 231(1.9) 219(14.7) 179(12.1)
N分期                
N1 973(63.4) 8 410(70.6) Z＝－5.807 <0.001 938(63.1) 959(64.5) Z＝－0.708 0.479
N2 363(23.7) 2 323(19.5) 354(23.8) 335(22.5)
N3 198(12.9) 1 180(9.9) 195(13.1) 193(13.0)
组织学分级                
1级 147(9.6) 1 751(14.7) Z＝－9.575 <0.001 146(9.8) 129(8.7) Z＝－0.203 0.839
2级 714(46.5) 6 327(53.1) 701(47.1) 719(48.3)
3级 661(43.1) 3 800(31.9) 629(42.3) 635(42.7)
4级 12(0.8) 35(0.3) 11(0.7) 4(0.3)
放射治疗                
无 592(38.6) 4 432(37.2) χ2＝1.120 0.290 566(38.1) 553(37.2) χ2＝0.242 0.623
有 942(61.4) 7 481(62.8) 921(61.9) 934(62.8)
图1 腋窝淋巴结阳性Luminal A型乳腺癌患者的生存曲线　a、b图分别为PSM前后新辅助化疗和辅助化疗2组患者的生存曲线比较注：a图，χ2＝218.252, P<0.001；b图，χ2＝34.575, P<0.001
图2 不同腋窝淋巴结分期的腋窝淋巴结阳性Luminal A型乳腺癌患者生存曲线比较　a、b图分别为新辅助化疗和辅助化疗患者的总生存曲线注：a图，χ2＝96.422, P<0.001；b图，χ2＝47.205, P<0.001
图3 不同腋窝淋巴结分期的腋窝淋巴结阳性Luminal A型乳腺癌患者新辅助化疗和辅助化疗生存曲线比较　a、b、c图分别为N1、N2、N3腋窝不同分期患者新辅助化疗和辅助化疗的生存曲线注：a图，χ2＝11.585, P＝0.001；b图，χ2＝13.060, P<0.001；c图，χ2＝12.245, P<0.001
图4 不同腋窝淋巴结分期的腋窝淋巴结阳性Luminal A型乳腺癌患者有无放射治疗的生存曲线比较　a、b、c图分别为N1、N2、N3腋窝不同分期患者有无放射治疗的生存曲线注：a图，χ2＝1.441, P＝0.230；b图，χ2＝12.426, P<0.001；c图，χ2＝0.881, P＝0.348
表3 影响腋窝淋巴结阳性Lumina A型乳腺癌患者的预后Cox比例风险回归模型分析
临床病理特征 单因素分析 多因素分析
HR 95%CI P值 HR 95%CI P值
类型            
新辅助化疗 1     1    
辅助化疗 0.626 0.535~0.733 <0.001 0.613 0.523~0.719 <0.001
年龄            
<45岁 1     1    
45~60岁 1.134 0.926~1.390 0.225 1.092 0.889~1.342 0.399
>60岁 1.558 1.261~1.924 <0.001 1.438 1.158~1.785 0.001
种族            
白种人 1     1    
黑种人 1.450 1.188~1.771 <0.001 1.323 1.076~1.627 0.008
其他 0.515 0.368~0.719 <0.001 0.474 0.339~0.664 <0.001
婚姻状况            
已婚 1     1    
其他 1.319 1.130~1.540 <0.001 1.124 0.958~1.320 0.151
病理类型            
浸润性导管癌 1          
其他 0.963 0.807~1.149 0.675      
原发灶位置            
左侧 1          
右侧 0.921 0.789~1.075 0.294      
肿瘤分期            
Ⅰ期 1     1    
Ⅱ期 1.899 0.704~5.125 0.205 1.094 0.392~3.053 0.864
Ⅲ期 4.359 1.629~11.662 0.003 1.745 0.610~4.988 0.299
T分期            
T0 1     1    
T1 0.091 0.028~0.291 <0.001 0.111 0.034~0.360 <0.001
T2 0.169 0.054~0.529 0.002 0.183 0.058~0.576 0.004
T3 0.203 0.065~0.636 0.006 0.170 0.053~0.546 0.003
T4 0.404 0.129~1.267 0.120 0.282 0.088~0.908 0.034
N分期            
N1 1     1    
N2 1.605 1.332~1.935 <0.001 1.145 0.894~1.465 0.284
N3 3.000 2.480~3.629 <0.001 2.007 1.582~2.547 <0.001
组织学分级            
1级 1     1    
2级 1.222 0.867~1.723 0.252 1.164 0.824~1.644 0.388
3级 2.507 1.796~3.501 <0.001 2.296 1.640~3.215 <0.001
4级 1.003 0.242~4.159 0.996 0.714 0.172~2.964 0.643
放射治疗            
无 1          
有 0.949 0.809~1.113 0.517      
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