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中华乳腺病杂志(电子版) ›› 2022, Vol. 16 ›› Issue (04) : 212 -218. doi: 10.3877/cma.j.issn.1674-0807.2022.04.003

论著

乳腺癌新辅助全身治疗后病理完全缓解的预测因子:一项单中心回顾性研究
冉秋燕1, 付萍1, 魏世蓉1, 肖何2, 徐琰3, 赵连花1,()   
  1. 1. 400042 重庆,陆军军医大学大坪医院病理科
    2. 400042 重庆,陆军军医大学大坪医院肿瘤科
    3. 400042 重庆,陆军军医大学大坪医院普外科
  • 收稿日期:2021-07-23 出版日期:2022-08-01
  • 通信作者: 赵连花
  • 基金资助:
    陆军特色医学中心2019年临床医学技术创新能力培养计划资助项目(2019CXLCC015)

Predictors of pathological complete response after neoadjuvant therapy in breast cancer: a single-center retrospective study

Qiuyan Ran1, Ping Fu1, Shirong Wei1, He Xiao2, Yan Xu3, Lianhua Zhao1,()   

  1. 1. Department of Pathology, Daping Hospital, Army Medical University, Chongqing 400042, China
    2. Department of Oncology, Daping Hospital, Army Medical University, Chongqing 400042, China
    3. Department of General Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China
  • Received:2021-07-23 Published:2022-08-01
  • Corresponding author: Lianhua Zhao
引用本文:

冉秋燕, 付萍, 魏世蓉, 肖何, 徐琰, 赵连花. 乳腺癌新辅助全身治疗后病理完全缓解的预测因子:一项单中心回顾性研究[J/OL]. 中华乳腺病杂志(电子版), 2022, 16(04): 212-218.

Qiuyan Ran, Ping Fu, Shirong Wei, He Xiao, Yan Xu, Lianhua Zhao. Predictors of pathological complete response after neoadjuvant therapy in breast cancer: a single-center retrospective study[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2022, 16(04): 212-218.

目的

探讨乳腺癌患者新辅助全身治疗(NST)后病理完全缓解(pCR)的预测因子。

方法

回顾性分析2016年1月1日至2021年3月1日在陆军军医大学大坪医院行空芯针穿刺活组织检查诊断为乳腺浸润性癌,并且接受NST后行手术切除的516例患者临床病理资料,包括患者年龄、月经状态、临床分期、NST方案及周期、组织学类型、组织学分级、ER表达、PR表达、HER-2表达、Ki-67表达、分子分型及术后Miller-Payne(MP)病理评级(G1、G2、G3、G4、G5)。pCR被定义为G5并且区域淋巴结阴性。采用Kruskal-Wallis H检验分析不同临床病理特征组间MP病理评级,采用χ2检验分析不同临床病理特征组间pCR率的差异。采用单因素和逐步向前Logistic回归模型分析pCR的独立预测因素。

结果

(1)MP病理评级:G4~G5(病理缓解组)123例(23.8%),G1~G3(病理未缓解组)393例(76.2%)。患者临床分期、ER表达、PR表达、HER-2表达、Ki-67表达、分子分型、NST方案、NST周期均与MP评级有关(χ2=13.572、19.687、18.963、17.989、15.493、27.605、31.622、10.103,P均<0.050)。pCR 59例(11.4%),非pCR 457例(88.6%)。患者月经状态、组织学分级、ER表达、PR表达、HER-2表达、Ki-67表达、分子分型、NST方案、NST周期均与pCR有关(χ2=3.898、9.854、30.593、17.582、20.611、9.303、33.286、34.546、13.846,P均<0.050)。(2)各分子分型间病理缓解率的差异有统计学意义(χ2=42.117,P<0.001)。(3)多因素Logistic回归分析显示:绝经前患者、临床Ⅲ~Ⅳ期、组织学分级为3级、NST方案含有靶向药物、HER-2阳性型和basal-like型是pCR率增高的独立预测因素(OR=0.475, 95%CI:0.256~0.881, P=0.018;OR=0.487, 95%CI: 0.238~0.998, P=0.049;OR=2.108, 95%CI: 1.073~4.141, P=0.030;OR=5.576, 95%CI: 1.958~15.874, P=0.001;OR=10.128, 95%CI: 1.076~95.312, P=0.043;OR=18.497, 95%CI: 2.254~151.815, P=0.007)。(4)临床Ⅲ~Ⅳ期、NST方案含有靶向药物、NST周期≥5个周期、luminal B(HER-2阴性)型、luminal B(HER-2阳性)型、HER-2阳性型和basal-like型是病理缓解率增高的独立预测因素(OR=0.436, 95%CI:0.258~0.738, P=0.002;OR=2.305, 95%CI:1.109~4.792, P=0.025;OR=2.718, 95%CI: 1.121~6.588, P=0.027;OR=6.764, 95%CI: 1.950~23.463, P=0.003;OR=8.094, 95%CI:2.048~31.989, P=0.003;OR=12.125, 95%CI: 3.097~47.460, P<0.001;OR=17.182, 95%CI: 4.874~60.577, P<0.001)。

结论

luminal B(HER-2阳性)型、HER-2阳性型及basal-like型(较之于luminal A型)、临床分期早、组织学分级高、ER和PR阴性、HER2阳性、Ki-67高表达、NST周期≥5个及采用了靶向治疗的患者具有较高的pCR率;而月经状态、临床分期、组织学分级、分子分型及NST方案是pCR的独立预测因子。

Objective

To investigate the predictors of pathological complete response (pCR) after neoadjuvant systemic therapy(NST) in breast cancer patients.

Methods

The clinicopathological data of 516 patients with invasive breast cancer who underwent core needle biopsy and surgical resection after NST in the Daping Hospital, Army Medical University from January 1, 2016 to March 1, 2021 were retrospectively analyzed, including patient age, menstrual status, clinical stage, NST regimen and cycle, histological type, histological grade, ER expression, PR expression, HER-2 expression, Ki-67 expression, molecular subtype and postoperative Miller-Payne grades (G1, G2, G3, G4, G5). pCR was defined as G5 with negative regional lymph nodes. The Kruskal-Wallis H test was used to compare the Miller-Payne grades among patients with different clinicopathological characteristics, and χ2 test was used to compare the pCR rates. Univariate and forward stepwise logistic regression models were used to analyze independent predictors of pCR.

Results

(1) According to the Miller-Payne grades, there were 123 cases (23.8%) of G4-G5 (pathological remission group), and 393 cases (76.2%) of G1-G3 (non-pathological remission group). Clinical stage, ER expression, PR expression, HER-2 expression, Ki-67 expression, molecular subtypes, NST regimen and NST cycle were all related to the patients’ Miller-Payne grades (χ2=13.572, 19.687, 18.963, 17.989, 15.493, 27.605, 31.622, 10.103, all P<0.050). There were 59 cases (11.4%) of pCR and 457 cases (88.6%) of non-pCR. Menstrual status, histological grade, ER expression, PR expression, HER-2 expression, Ki-67 expression, molecular subtypes, NST regimen, and NST cycle were all related to the patients’ pCR (χ2=3.898, 9.854, 30.593, 17.582, 20.611, 9.303, 33.286, 34.546, 13.846, all P<0.050). (2) The pathological remission rate showed a significant difference among molecular subtypes (χ2=42.117, P<0.001). (3) The logistic regression analysis showed that premenopausal status, clinical stage Ⅲ-Ⅳ, histological grade 3, targeted drugs in NST regimen, HER-2 positive subtype and basal-like subtype were independent predictive factors of increased pCR rate (OR=0.475, 95%CI: 0.256-0.881, P=0.018; OR=0.487, 95%CI: 0.238-0.998, P=0.049; OR=2.108, 95%CI: 1.073-4.141, P=0.030; OR=5.576, 95%CI: 1.958-15.874, P=0.001; OR=10.128, 95%CI: 1.076-95.312, P=0.043; OR=18.497, 95%CI: 2.254-151.815, P=0.007). (4) Clinical stage Ⅲ-Ⅳ, targeted drugs in NST regimen, NST cycles≥5, luminal B (HER-2 negative) subtype, luminal B (HER-2 positive) subtype, HER-2 positive subtype and basal-like subtype were independent predictive factors of increased pathological remission rate (OR=0.436, 95%CI: 0.258-0.738, P=0.002; OR=2.305, 95%CI: 1.109-4.792, P=0.025; OR=2.718, 95%CI: 1.121-6.588, P=0.027; OR=6.764, 95%CI: 1.950-23.463, P=0.003; OR=8.094, 95%CI: 2.048-31.989, P=0.003; OR=12.125, 95%CI: 3.097-47.460, P<0.001; OR=17.182, 95%CI: 4.874-60.577, P<0.001).

Conclusions

The patients with luminal B (HER-2 positive), HER-2 positive and basal-like subtypes (compared with luminal A subtype), early clinical stage, advanced histological grade, ER and PR negative, HER-2 positive, high Ki-67 expression, NST cycles≥ 5 and targeted therapy have higher pCR rates. Menstrual status, clinical stage, histological grade, molecular subtype and NST regimen were independent predictors of pCR.

表1 516例乳腺癌患者新辅助治疗后pCR和病理缓解影响因素的Logistic回归分析变量赋值表
表2 516例乳腺癌患者的临床病理特征与新辅助治疗后病理疗效的关系[例(%)]
临床病理特征 例数 新辅助治疗后MP病理评级 χ2 P pCR χ2 P
G1 G2 G3 G4 G5
年龄                      
  ≥35岁 498 27(5.4) 191(38.4) 161(32.3) 63(12.7) 56(11.2) 0.355 0.551 56(11.2) 0.111 0.739
  <35岁 18 1(5.6) 5(27.8) 8(44.4) 1(5.6) 3(16.7) 3(16.7)
月经状态                      
  绝经前 270 14(5.2) 98(36.3) 96(35.6) 24(8.9) 38(14.1) 0.543 0.461 38(14.1) 3.898 0.048
  绝经后 246 14(5.7) 98(39.8) 73(29.7) 40(16.3) 21(8.5) 21(8.5)
临床分期                      
  Ⅰ期 31 1(3.2) 4(12.9) 13(41.9) 9(29.0) 4(12.9) 13.572 0.004 4(12.9) 5.174 0.159
  Ⅱ期 319 15(4.7) 125(39.2) 95(29.8) 41(12.9) 43(13.5) 43(13.5)
  Ⅲ期 143 11(7.7) 58(40.6) 54(37.8) 11(7.7) 9(6.3) 9(6.3)
  Ⅳ期 23 1(4.3) 9(39.1) 7(30.4) 3(13.0) 3(13.0) 3(13.0)
组织学类型                      
  浸润性导管癌 513 28(5.5) 195(38.0) 168(32.7) 63(12.3) 59(11.5) 1.549 0.461 59(11.5) 0.947 1.000
  浸润性小叶癌 1 0(0) 0(0) 0(0) 1(100) 0(0) 0(0)
  混合性癌 2 0(0) 1(50) 1(50) 0(0) 0(0) 0(0)
组织学分级                      
  1级 13 0(0) 7(53.8) 4(30.8) 2(15.4) 0(0) 1.820 0.402 0(0) 9.854 0.007
  2级 402 21(5.2) 154(38.3) 137(34.1) 51(12.7) 39(9.7) 39(9.7)
  3级 101 7(6.9) 35(34.7) 28(27.7) 11(10.9) 20(19.8) 20(19.8)
ER表达                      
  阳性 311 12(3.9) 138(44.4) 117(37.6) 28(9.0) 16(5.1) 19.687 <0.001 16(5.1) 30.593 <0.001
  弱阳性 23 2(8.7) 5(21.7) 5(21.7) 6(26.1) 5(21.7) 5(21.7)
  阴性 182 14(7.7) 53(29.1) 47(25.8) 30(16.5) 38(20.9) 38(20.9)
PR表达                      
  阳性 222 8(3.6) 105(47.3) 86(38.7) 12(5.4) 11(5.0) 18.963 <0.001 11(5.0) 17.582 <0.001
  弱阳性 52 1(1.9) 18(34.6) 18(34.6) 9(17.3) 6(11.5) 6(11.5)
  阴性 242 19(7.9) 73(30.2) 65(26.9) 43(17.8) 42(17.4) 42(17.4)
HER-2状态                      
  阳性 171 10(5.8) 46(26.9) 55(32.2) 25(14.6) 35(20.5) 17.989 <0.001 35(20.5) 20.611 <0.001
  阴性 345 18(5.2) 150(43.5) 114(33.0) 39(11.3) 24(7.0) 24(7.0)
Ki-67表达                      
  <14% 159 7(4.4) 79(49.7) 55(34.6) 10(6.3) 8(5.0) 15.493 <0.001 8(5.0) 9.303 0.002
  ≥14% 357 21(5.9) 117(32.8) 114(31.9) 54(15.1) 51(14.3) 51(14.3)
分子分型                      
  luminal A型 88 2(2.3) 50(56.8) 33(37.5) 2(2.3) 1(1.1) 27.605 <0.001 1(1.1) 33.286 <0.001
  luminal B(HER-2阴性)型 166 8(4.8) 69(41.6) 60(36.1) 21(12.7) 8(4.8) 8(4.8)
  luminal B(HER-2阳性)型 86 4(4.7) 25(29.1) 30(34.9) 11(12.8) 16(18.6) 16(18.6)
  HER-2阳性型 84 6(7.1) 22(26.2) 24(28.6) 13(15.5) 19(22.6) 19(22.6)
  basal-like型 92 8(8.7) 30(32.6) 22(23.9) 17(18.5) 15(16.3) 15(16.3)
新辅助治疗方案                      
  化疗 400 23(5.8) 173(43.2) 128(32.0) 48(12.0) 28(7.0) 31.622 <0.001 28(7.0) 34.546 <0.001
  化疗+靶向治疗 116 5(4.3) 23(19.8) 41(35.3) 16(13.8) 31(26.7) 31(26.7)
新辅助治疗周期                      
  1~2个 62 3(4.8) 32(51.6) 20(32.3) 4(6.5) 3(4.8) 10.103 0.018 3(4.8) 13.846 0.003
  3~4个 255 11(4.3) 97(38.0) 92(36.1) 34(13.3) 21(8.2) 21(8.2)
  5~6个 164 11(6.7) 60(36.6) 46(28.0) 20(12.2) 27(16.5) 27(16.5)
  >6个 35 3(8.6) 7(20) 11(31.4) 6(17.1) 8(22.9) 8(22.9)
表3 不同分子分型乳腺癌患者新辅助治疗后病理缓解情况比较[例(%)]
表4 预测乳腺癌患者新辅助治疗后为pCR和病理缓解的单因素Logistic回归分析(n=516)
表5 预测乳腺癌患者新辅助治疗后pCR和病理缓解的逐步向前Logistic回归结果(n=516)
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