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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2022, Vol. 16 ›› Issue (05) : 270 -275. doi: 10.3877/cma.j.issn.1674-0807.2022.05.002

论著

激素受体阳性、人表皮生长因子受体2阴性的女性乳腺癌患者21基因复发风险评分与临床病理特征的关系
邓旭1, 朱枫1, 闫战涛1, 雷婷1, 李青1,†()   
  1. 1. 213003　常州，苏州大学附属第三医院病理科
  • 收稿日期:2022-03-14 出版日期:2022-10-01
  • 通信作者: 李青
  • 基金资助:
    常州市卫健委青年人才科技项目(QN202114)

Correlation between 21-gene recurrence score and clinicopathological characteristics of HR-positive and HER-2-negative female breast cancer patients

Xu Deng1, Feng Zhu1, Zhantao Yan1, Ting Lei1, Qing Li1,†()   

  1. 1. Department of Pathology, Third Affiliated Hospital of Soochow University, Changzhou 213003, China
  • Received:2022-03-14 Published:2022-10-01
  • Corresponding author: Qing Li
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引用本文：

邓旭, 朱枫, 闫战涛, 雷婷, 李青. 激素受体阳性、人表皮生长因子受体2阴性的女性乳腺癌患者21基因复发风险评分与临床病理特征的关系[J]. 中华乳腺病杂志(电子版), 2022, 16(05): 270-275.

Xu Deng, Feng Zhu, Zhantao Yan, Ting Lei, Qing Li. Correlation between 21-gene recurrence score and clinicopathological characteristics of HR-positive and HER-2-negative female breast cancer patients[J]. Chinese Journal of Breast Disease(Electronic Edition), 2022, 16(05): 270-275.

目的

探讨激素受体(HR)阳性、HER-2阴性女性乳腺癌患者21基因复发风险评分(RS)与临床病理特征之间的关系及其在不同BMI患者中的分布差异，分析21基因RS在乳腺癌患者个体化治疗中的指导意义。

方法

回顾性分析2017年9月至2021年8月苏州大学附属第三医院收治的142例手术切除并经病理确诊的HR阳性、HER-2阴性女性乳腺癌患者的临床病理资料。采用实时荧光定量聚合酶链式反应检测21基因的表达，并计算RS值。根据RS将患者分为低(RS≤15)、中(15<RS<26)、高RS(RS≥26) 3个亚组；根据BMI将患者分为正常组(BMI<24.0 kg/m2 )、超重组(24.0 kg/m2≤BMI<28.0 kg/m2)和肥胖组(BMI≥28.0 kg/m2 )3个亚组。采用χ2检验或Fisher确切概率法分析不同RS分组及不同BMI分组患者临床病理特征之间的差异，组间两两比较采用卡方分割法，并进一步对有统计学意义的连续变量资料进行线性相关分析。RS为非正态分布的计量资料，采用M(P25，P75)表示，组间比较采用非参数秩和检验；等级资料(组织学分级)采用非参数秩和检验。传统术后风险分组和21基因RS分组方法的比较采用McNemar检验。

结果

根据RS将患者分为低(n＝105)、中(n＝ 21)、高(n＝16)3组，根据BMI将患者分为体重正常组(n＝83)、超重组(n＝48)、肥胖组(n＝11)。不同RS分组乳腺癌患者组织学分级(H＝13.824，P＝0.001)、PR表达水平(χ2＝18.884，P<0.001)、Ki-67(χ2＝15.483，P<0.001)及分子分型(χ2＝12.986，P＝0.002)比较，差异均有统计学意义。RS与PR表达水平呈负相关(r＝－0.520，P<0.001)、与Ki-67呈正相关(r＝0.487，P<0.001)。不同BMI状态乳腺癌患者年龄(χ2＝8.401，P＝0.015)及绝经状态(χ2＝9.060，P＝0.011)比较，差异具有统计学意义。体重正常组、超重组和肥胖组的RS及其分布差异均无统计学意义(H＝0.460，P＝0.795；χ2＝3.042，P＝0.537)。RS分组和传统术后复发风险分组比较，差异具有统计学意义(χ2＝55.850，P<0.001)。根据21基因RS，重新归类为低RS组的72例传统术后中复发风险的患者中仅19人接受了化疗，术后随访7.0~54.0个月(中位时间：22.5个月)，截至2022年3月均未见复发或疾病进展。

结论

21基因RS可为早期HR阳性、HER-2阴性乳腺癌患者的术后辅助化疗提供依据。

关键词: 乳腺肿瘤, 分子分型, 21基因, 复发
Objective

To investigate the correlation between the 21-gene recurrence score (RS)and clinicopathological characteristics of women with hormone receptor(HR)-positive, HER-2-negative breast cancer, and RS distribution in patients with different body mass index(BMI)and to explore the clinical significance of RS in the personalized treatment of breast cancer patients.

Methods

The clinicopathological data of 142 female patients with HR-positive, HER-2-negative breast cancer, which were surgically resected and pathologically confirmed in the Third Affiliated Hospital of Soochow University from September 2017 to August 2021, were retrospectively analyzed. The expression of 21 genes was detected by real-time fluorescence quantitative polymerase chain reaction and RS was calculated. According to RS, patients were divided into three subgroups: low (RS≤15), medium (15<RS<26), and high RS (RS≥26); According to BMI, patients were divided into three subgroups: normal weight group (BMI<24.0 kg/m2), overweight(24.0 kg/m2≤BMI<28.0 kg/m2), and obese group (BMI≥28 kg/m2). χ2 test or Fisher’s exact test was used to compare the clinicopathological characteristics among different RS groups and different BMI groups. The linear correlation analysis was conducted on continuous variables with statistical significance. Because of skewed distribution, RS was expressed as M (P25, P75), and compared using nonparametric rank sum test between groups. The nonparametric rank sum test was used for graded data (histological grades). The McNemar test was used to compare the traditional postoperative recurrence risk grouping and 21-gene RS grouping.

Results

According to RS, patients were divided into low (n=105), medium (n=21) and high RS group (n=16), and according to BMI, patients were divided into normal weight group (n=83), overweight (n=48) and obese group (n=11). Statistically significant differences were found in the tissue grade(H=13.824, P=0.001), PR expression(χ2=18.884, P<0.001), Ki-67(χ2=15.483, P<0.001)and molecular typing (χ2=12.986, P=0.002)among different RS groups. Further analysis showed that RS was negatively correlated with PR expression (r=-0.520, P<0.001)and positively correlated with Ki-67(r=0.487, P<0.001). Statistically significant differences were found in the age(χ2=8.401, P=0.015)and menopausal status(χ2=9.060, P=0.011)among different BMI groups. No significant difference was found in RS value(H=0.460, P=0.795)and its distribution(χ2=3.042, P=0.537)among normal weight group, overweight group and obese group. There was a significant difference between the RS grouping and the traditional postoperative recurrence risk grouping(χ2=55.850, P<0.001). Only 19 out of 72 patients were reclassified as low recurrence risk group according to 21-gene RS from intermediate traditional postoperative recurrence risk group and received adjuvant chemotherapy. The postoperative follow-up period was 7.0-54.0 months (median: 22.5 months). Until March 2022, no recurrence or disease progression was observed.

Conclusion

The 21-gene RS could provide a reference for the adjuvant chemotherapy of patients with early HR-positive, HER-2-negative breast cancer.

Key words: Breast neoplasms, Molecular typing, 21 gene, Recurrence
表1 不同复发风险评分分组乳腺癌患者的临床病理特征比较[例(%)]
临床病理特征 低RS组(n＝105) 中RS组(n＝21) 高RS组(n＝16) 检验值 P值
年龄          
  <55岁 52(49.5) 7(33.3) 7(7/16) χ2＝1.898 0.387
  ≥55岁 53(50.5) 14(66.7) 9(9/16)
绝经状态          
  否 49(46.7) 7(33.3) 6(6/16) χ2＝1.543 0.462
  是 56(53.3) 14(66.7) 10(10/16)
肿瘤直径          
  ≤2 cm 86(81.9) 17(81.0) 10(10/16) χ2＝3.148 0.199
  >2 cm 19(18.1) 4(19.0) 6(6/16)
病理分型          
  浸润性导管癌 68(64.8) 18(85.7) 13(13/16) χ2＝4.775 0.092
  其他 37(35.2) 3(14.3) 3(3/16)
组织学分级          
  1级 12(16.7) 2(11.8) 0 H＝13.824 0.001
  2级 56(77.8) 14(82.3) 8(8/14)
  3级 4(5.5) 1(5.9) 6(6/14)a
PR          
  低表达 6(5.7) 2(9.5) 8(8/16) χ2＝18.884 <0.001
  高表达 99(94.3) 19(90.5) 8(8/16)b
Ki-67          
  <14% 60(57.1) 8(38.1) 1(1/16) χ2＝15.483 <0.001
  ≥14% 45(42.9) 13(61.9) 15(15/16)c
分子分型          
  luminal A型 56(53.3) 8(38.1) 1(1/16) χ2＝12.986 0.002
  luminal B型 49(46.7) 13(61.9) 15(15/16)d
表2 不同BMI分组乳腺癌患者的临床病理特征比较[例(%)]
临床病理特征 正常组(n＝83) 超重组(n＝48) 肥胖组(n＝11) 检验值 P值
年龄          
  <55岁 47(56.6) 16(33.3) 3(3/11) χ2＝8.401 0.015
  ≥55岁 36(43.4) 32(66.7)a 8(8/11)
绝经状态          
  否 45(54.2) 14(29.2) 3(3/11) χ2＝9.060 0.011
  是 38(45.8) 34(70.8)b 8(8/11)
肿瘤直径          
  ≤2 cm 68(81.9) 38(79.2) 7(7/11) χ2＝2.007 0.367
  >2 cm 15(18.1) 10(20.8) 4(4/11)
病理分型          
  浸润性导管癌 58(69.9) 34(70.8) 7(7/11) χ2＝0.222 0.895
  其他 25(30.1) 14(29.2) 4(4/11)
组织学分级a          
  1级 9(15.3) 5(13.5) 0 H＝0.978 0.613
  2级 44(74.6) 28(75.7) 6(6/7)
  3级 6(10.2) 4(10.8) 1(1/7)
PR          
  低表达 11(13.3) 4(8.3) 1(1/11) χ2＝0.793 0.673
  高表达 72(86.7) 44(91.7) 10(10/11)
Ki-67          
  <14% 45(54.2) 18(37.5) 6(6/11) χ2＝3.571 0.168
  ≥14% 38(45.8) 30(62.5) 5(5/11)
分子分型          
  luminal A型 43(51.8) 16(33.3) 6(6/11) χ2＝4.551 0.103
  luminal B型 40(48.2) 32(66.7) 5(5/11)
表3 不同BMI分组乳腺癌患者RS分布的比较[例(%)]
组别 例数 RS≤15 15<RS<26 RS≥26 χ2值 P值
正常组 83 61(73.5) 12(14.5) 10(12.0) 3.042 0.537
超重组 48 35(72.9) 9(18.8) 4(8.3)
肥胖组 11 9(9/11) 0 2(2/11)
表4 142例HR阳性、HER-2阴性乳腺癌患者传统术后复发风险分组与21基因RS分组的比较(例)
传统术后复发风险分组 21基因RS分组 χ2值 P值
低复发风险 中、高复发风险
低复发风险 33 6 55.850 <0.001
中、高复发风险 72 31
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