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孕激素受体与Ki-67指数组合对激素受体阳性中分化早期乳腺癌预后的评估价值

张燕娜,  周易冬,  茅枫,  姚儒,  孙强

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文章导航 > 协和医学杂志  > 2019 >  10(5): 539-545
张燕娜, 周易冬, 茅枫, 姚儒, 孙强. 孕激素受体与Ki-67指数组合对激素受体阳性中分化早期乳腺癌预后的评估价值[J]. 协和医学杂志, 2019, 10(5): 539-545. doi: 10.3969/j.issn.1674-9081.2019.05.019
引用本文: 张燕娜, 周易冬, 茅枫, 姚儒, 孙强. 孕激素受体与Ki-67指数组合对激素受体阳性中分化早期乳腺癌预后的评估价值[J]. 协和医学杂志, 2019, 10(5): 539-545. doi: 10.3969/j.issn.1674-9081.2019.05.019
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Yan-na ZHANG, Yi-dong ZHOU, Feng MAO, Ru YAO, Qiang SUN. Prognostic Value of Progesterone Receptor and Ki-67 Combination in Hormone Receptor Positive Grade 2 Early-stage Breast Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2019, 10(5): 539-545. doi: 10.3969/j.issn.1674-9081.2019.05.019
Citation: Yan-na ZHANG, Yi-dong ZHOU, Feng MAO, Ru YAO, Qiang SUN. Prognostic Value of Progesterone Receptor and Ki-67 Combination in Hormone Receptor Positive Grade 2 Early-stage Breast Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2019, 10(5): 539-545. doi: 10.3969/j.issn.1674-9081.2019.05.019
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孕激素受体与Ki-67指数组合对激素受体阳性中分化早期乳腺癌预后的评估价值

doi: 10.3969/j.issn.1674-9081.2019.05.019

  • 中国医学科学院 北京协和医学院 北京协和医院乳腺外科, 北京 100730

详细信息
    通讯作者:

    孙强 电话:010-69158703, E-mail:sunqiangpumc@sina.com

  • 中图分类号: R737.9

Prognostic Value of Progesterone Receptor and Ki-67 Combination in Hormone Receptor Positive Grade 2 Early-stage Breast Cancer

  • Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

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    摘要
  • 摘要:   目的  探讨孕激素受体(progesterone receptor, PR)及Ki-67指数(PK)组合对激素受体阳性腋窝淋巴结阴性中分化早期乳腺癌的预后评估价值。  方法  回顾性分析2012年5月至2017年5月于北京协和医院乳腺外科行手术治疗且行21基因检测的中分化早期乳腺癌患者的临床及病理资料, 根据21基因复发风险评分(recurrence score, RS)将患者分为RS低危组(RS < 18)、RS中危组(18 ≤ RS < 31)和RS高危组(RS ≥ 31), 同时按照PR表达及Ki-67指数设定PR与Ki-67指数组合, 将患者分为PK低危组(PR ≥ 10%且Ki-67 ≤ 20%)、PK高危组(PR < 10%且Ki-67>20%)及PK中危组(非高危或低危组), 分析并比较PK组合与RS评分的一致性。  结果  共389例符合纳入及排除标准的患者入选本研究, 其中RS低危组247例(63.5%, 247/389), RS中危组115例(29.6%, 115/389), RS高危组27例(6.9%, 27/389); PK低危组248例(63.8%, 248/389), PK中危组125例(32.1%, 125/389), PK高危组16例(4.1%, 16/389)。推荐的PK组合对RS低危组和高危组的预测敏感度分别为75.3%和37.0%, 阳性预测值分别为75.0%和62.5%, 不一致性分别为0.4%和6.3%。中位随访40个月的结果显示, PK低、中、高危组的总事件发生率分别为3.6%、7.2%和12.5%, RS低、中、高危组的总事件发生率分别为3.2%、8.7%和7.4%, 两组差异无统计学意义(χ2=0.200, P=0.655)。  结论  针对激素受体阳性腋窝淋巴结阴性中分化早期乳腺癌的PK组合具有与21基因RS评分相当的预后评估价值。
    Abstract:   Objective  To evaluate the prognostic value of the combination of progesterone receptor (PR) and Ki-67 index in grade 2 breast cancer with positive hormone receptor (HR) and negative axillary lymph node.  Methods  The clinical and pathological data of patients with grade 2 breast cancer who underwent surgical treatment and 21 genes' recurrence score (RS) testing in the department of Breast Surgery, Peking Union Medical College Hospital from May 2012 to May 2017 were retrospectively analyzed. According to the 21 genes' RS, patients were divided into RS low-risk group (RS < 18), RS intermediate-risk group (18≤RS < 31), and RS high-risk group (RS≥31). At the same time, the combination of PR and Ki-67 index (PK) was set according to the expression of PR and Ki-67 index. The patients were divided into PK low-risk group (PR≥10% and Ki-67≤20%), PK high-risk group (PR < 10% and Ki-67>20%), and PK intermediate-risk group (non-high or low-risk group). The consistency of the PK combination and 21 genes' RS was analyzed and compared.  Results  A total of 389 patients who met the inclusive and exclusive criteria were enrolled in this study, including 247 patients in RS low-risk group (63.5%, 247/389), 115 in RS intermediate risk group (29.6%, 115/389), 27 in RS high-risk group (6.9%, 27/389), 248 in PK low-risk group (63.8%, 248/389), 125 in PK intermediate risk group (32.1%, 125/389), 16 in PK high-risk group (4.1%, 16/389). The predictive sensitivity of the recommended PK combination for RS low risk and high-risk group was 75.3% and 37.0%, respectively, with the positive predictive values of 75.0% and 62.5%, and the inconsistency of 0.4% and 6.3%, respectively. After a median follow-up of 40 months, the total incidence of locoregional recurrence (LRR) and distant metastasis (DM) in PK low, intermediate, and high-risk group was 3.6%, 7.2%, and 12.5%, respectively. The total incidence of LRR and DM in RS low, intermediate, and high-risk groups was 3.2%, 8.7%, and 7.4%, respectively. There was no significant difference between PK combination and RS (P=0.655).  Conclusion  The prognostic value of PK combination for HR-positive grade 2 early-stage breast cancer with negative axillary lymph nodes is comparable to that of the 21 genes' RS.
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  • 表  1  不同组织学分级早期乳腺癌RS分组[n(%)]

    组织学分级 RS低危组 RS中危组 RS高危组 χ2值 P值
    Ⅰ级(n=136) 117(86.0) 18(13.2) 1(0.7)
    Ⅱ级(n=389) 247(63.5) 115(29.6) 27(6.9) 76.26 ＜0.001
    Ⅲ级(n=48) 17(35.4) 15(31.3) 16(33.3)
    RS:复发风险评分
    下载: 导出CSV

    表  2  389例中分化早期乳腺癌患者不同RS分组的临床病理资料[n(%)]

    临床病理特征 RS低危组(n=247) RS中危组(n=115) RS高危组(n=27) χ2值 P值
    病理类型
      IDC 212(85.8) 108(69.7) 26(96.3)
      ILC 26(10.5) 7(30.3) 0(0)
      IDC+ILC 6(2.4) 0(0) 1(3.7)
      其他 3(1.2) 0(0) 0(0)
    肿瘤大小(cm) 7.01 0.135
      ≤2 233(94.3) 102(88.7) 23(85.2)
      ＞2 14(5.7) 12(10.4) 4(14.8)
      不详 0(0) 1(0.9) 0(0)
    ER表达 13.44 0.001
      阳性 247(100) 115(100) 26(96.3)
      阴性 0(0) 0(0) 1(3.7)
    PR表达 32.32 ＜0.001
      0 10(4.0) 12(10.4) 7(25.9)
      1~9 4(1.6) 5(4.3) 3(11.1)
      10~19 6(2.4) 7(6.1) 1(3.7)
      20~100 227(91.9) 91(79.1) 16(59.3)
    Ki-67指数(%) 72.21 ＜0.001
      ≤20 199(80.6) 73(63.5) 1(3.7)
      ＞20 48(19.4) 42(36.5) 26(96.3)
    乳腺手术方式 0.86 0.651
      保留乳腺 86(34.8) 39(33.9) 7(25.9)
      全切乳腺 161(65.2) 76(66.1) 20(74.1)
    腋窝淋巴结手术方式 4.22 0.122
      前哨淋巴结活检 73(29.6) 34(29.6) 3(11.1)
      腋窝淋巴结清扫 174(70.4) 81(70.4) 24(88.9)
    内分泌治疗 7.45 0.489
      SERM 155(62.8) 72(62.6) 13(48.1)
      AI 88(35.6) 38(33.0) 13(48.1)
      SERM-AI 2(0.8) 2(1.7) 1(3.7)
      OFS 0(0) 1(0.9) 0(0)
      未服药 2(0.8) 2(1.7) 0(0)
    化疗 168.03 ＜0.001
      是 8(3.2) 26(22.6) 26(96.3)
      否 239(96.8) 89(77.4) 1(3.7)
    RS：同表 1；IDC：浸润性导管癌；ILC：浸润性小叶癌；SERM：选择性雌激素受体调节剂；AI:芳香化酶抑制剂；OFS：卵巢功能抑制
    下载: 导出CSV

    表  3  PK组合对复发风险预估与RS分组的关系(n)

    PK分组 RS分组
    低危组(n=247) 中危组
    (n=115)     		高危组
    (n=27)
    低危组(n=248) 186 61 1
    中危组(n=125) 60 49 16
    高危组(n=16) 1 5 10
    RS：同表 1；PK组合：孕激素受体与Ki-67指数组合
    下载: 导出CSV

    表  4  不同PK组合对RS分组预估的一致性比较

    一致性指标 PK组合 RS低危组(%) RS高危组(%)
    敏感度 1 75.3 37.0
    2 55.8 37.0
    阳性预测值 1 75.0 62.5
    2 79.3 35.7
    不一致性 1 0.4 6.3
    2 0 17.9
    RS：同表 1；PK组合：同表 3；PK组合1：以PR≥10%且Ki-67≤20%为低危，以PR＜10%且Ki-67＞20%为高危；PK组合2：以PR≥20%且Ki-67≤20%为低危，以PR＜20%且Ki-67＞20%为高危
    下载: 导出CSV

    表  5  不同RS分组及PK分组事件数比较[n(%)]

    组别 发生事件数
    局部复发 远处转移
    RS分组
      低危组(n=247) 5(2.0) 3(1.2)
      中危组(n=115) 7(6.1) 3(2.6)
      高危组(n=27) 2(7.4) 0(0)
    PK分组
      低危组(n=248) 6(2.4) 3(1.2)
      中危组(n=125) 6(4.8) 3(2.4)
      高危组(n=16) 2(12.5) 0(0)
    χ2值 0.200
    P值 0.655
    RS：同表 1；PK组合：同表 3
    下载: 导出CSV
    • 参考文献(21)
  • [1] Gradishar WJ, Anderson BO, Balassanian R, et al. Invasive Breast Cancer Version 1.2016, NCCN Clinical Practice Guidelines in Oncology[J]. J Natl Compr Canc Netw, 2016, 14:324-354. doi:  10.6004/jnccn.2016.0037
    [2] Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer:results from NSABP B-14 and NSABP B-20[J]. J Clin Oncol, 2010, 28:1677-1683. doi:  10.1200/JCO.2009.23.7610
    [3] Zhang YN, Zhou YD, Mao F, et al. Impact of the 21-Gene Recurrence Score Assay in adjuvant chemotherapy selection for node-negative, hormone receptor-positive breast cancer in the Chinese population[J]. Neoplasma, 2015, 62:658-665. doi:  10.4149/neo_2015_079
    [4] Toi M, Iwata H, Yamanaka T, et al. Clinical significance of the 21-gene signature(Oncotype DX) in hormone receptor-positive early stage primary breast cancer in the Japanese population[J]. Cancer, 2010, 116:3112-3118. doi:  10.1002/cncr.25206
    [5] Lee MH, Han W, Lee JE, et al. The clinical impact of 21-gene recurrence score on treatment decisions for patients with hormone receptor-positive early breast cancer in Korea[J]. Cancer Res Treat, 2015, 47:208-214. http://europepmc.org/articles/PMC4398124/
    [6] Henry NL, Braun TM, Ali HY, et al. Associations between use of the 21-gene recurrence score assay and chemotherapy regimen selection in a statewide registry[J]. Cancer, 2017, 123:948-956. doi:  10.1002/cncr.30429
    [7] Zeng Y, Li Q, Qin T, et al. Impact of a 21-Gene Recurrence Score Test on the Choice of Adjuvant Chemotherapy for Hormone Receptor-positive Early-stage Breast Cancer:A Prospective Study[J]. Anticancer Res, 2017, 37:4539-4547. http://www.ncbi.nlm.nih.gov/pubmed/28739750
    [8] 张燕娜, 周易冬, 茅枫, 等. 21基因检测复发风险评分在激素受体阳性早期乳腺癌临床治疗和预后评估中的价值[J].中华肿瘤杂志, 2018, 2:110-114. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zhzl201802006
    [9] Thakkar JP, Mehta DG. A review of an unfavorable subset of breast cancer:estrogen receptor positive progesterone receptor negative[J]. Oncologist, 2011, 16:276-285. doi:  10.1634/theoncologist.2010-0302
    [10] Prat A, Cheang MC, Martin M, et al. Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer[J]. J Clin Oncol, 2013, 31:203-209. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=5411e2931d23233da9ce5fe94600509c
    [11] Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer:highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013[J]. Ann Oncol, 2013, 24:2206-2223. doi:  10.1093/annonc/mdt303
    [12] Kurozumi S, Matsumoto H, Hayashi Y, et al. Power of PgR expression as a prognostic factor for ER-positive/HER2-negative breast cancer patients at intermediate risk classified by the Ki67 labeling index[J]. BMC Cancer, 2017, 17:354-362. doi:  10.1186/s12885-017-3331-4
    [13] Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67[J]. J Immunol, 1984, 133:1710-1715. http://www.tandfonline.com/servlet/linkout?suffix=cit0008&dbid=8&doi=10.1080%2F2162402X.2015.1066062&key=6206131
    [14] Nishimura R, Osako T, Okumura Y, et al. Clinical significance of Ki-67 in neoadjuvant chemotherapy for primary breast cancer as a predictor for chemosensitivity and for prognosis[J]. Breast Cancer, 2010, 17:269-275. doi:  10.1007/s12282-009-0161-5
    [15] Honma N, Horii R, Iwase T, et al. Ki-67 evaluation at the hottest spot predicts clinical outcome of patients with hormone receptor-positive/HER2-negative breast cancer treated with adjuvant tamoxifen monotherapy[J]. Breast Cancer, 2015, 22:71-78. doi:  10.1007/s12282-013-0455-5
    [16] Curigliano G, Burstein HJ, P Winer E, et al. De-escalating and escalating treatments for early-stage breast cancer:the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017[J]. Ann Oncol, 2017, 28:1700-1712. doi:  10.1093/annonc/mdx308
    [17] Varga Z, Diebold J, Dommann-Scherrer C, et al. How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of Breast and Gynecopathologists[J]. PLoS One, 2012, 7:e37379. doi:  10.1371/journal.pone.0037379
    [18] Flanagan MB, Dabbs DJ, Brufsky AM, et al. Histopa-thologic variables predict Oncotype DX recurrence score[J]. Mod Pathol, 2008, 21:1255-1261. http://www.nature.com/modpathol/journal/v21/n10/abs/modpathol200854a.html
    [19] Cuzick J, Dowsett M, Pineda S, et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer[J]. J Clin Oncol, 2011, 29:4273-4278. doi:  10.1200/JCO.2010.31.2835
    [20] Geradts J, Bean SM, Bentley RC, et al. The oncotype DX recurrence score is correlated with a composite index including routinely reported pathobiologic features[J]. Cancer Invest, 2010, 28:969-977. doi:  10.3109/07357907.2010.512600
    [21] Turner BM, Skinner KA, Tang P, et al. Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score[J]. Mod Pathol, 2015, 28:921-931. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=fb2bfaca0f340dad9a678b4060cee5e8
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