切换至 "中华医学电子期刊资源库"
高级检索
中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2017, Vol. 11 ›› Issue (06) : 343 -348. doi: 10.3877/cma.j.issn.1674-0807.2017.06.005

论著

ER(-)/PR(+)乳腺癌的临床病理特点及预后分析
孙亚冬1, 李连方1, 刘山青1, 李永1, 张崇建1, 毛启新1, 申衍1, 崔树德1,†()   
  1. 1.450008 郑州大学附属肿瘤医院乳腺科
  • 收稿日期:2016-12-11 出版日期:2017-12-01
  • 通信作者: 崔树德

Clinicopathological characteristics and prognosis analysis of ER(-)/PR(+) breast cancer

Yadong Sun1, Lianfang Li1, Shanqing Liu1, Yong Li1, Chongjian Zhang1, Qixin Mao1, Yan Shen1, Shude Cui1,†()   

  1. 1.Department of Breast Diseases, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China
  • Received:2016-12-11 Published:2017-12-01
  • Corresponding author: Shude Cui
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

孙亚冬, 李连方, 刘山青, 李永, 张崇建, 毛启新, 申衍, 崔树德. ER(-)/PR(+)乳腺癌的临床病理特点及预后分析[J/OL]. 中华乳腺病杂志(电子版), 2017, 11(06): 343-348.

Yadong Sun, Lianfang Li, Shanqing Liu, Yong Li, Chongjian Zhang, Qixin Mao, Yan Shen, Shude Cui. Clinicopathological characteristics and prognosis analysis of ER(-)/PR(+) breast cancer[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2017, 11(06): 343-348.

目的

探讨ER(-)/PR(+)乳腺癌的临床病理特点及预后。

方法

回顾性分析2005 年1 月至2008 年12 月郑州大学附属肿瘤医院乳腺科收治的762 例乳腺癌患者的临床病理资料。 根据ER、PR 表达情况将患者分为3 组,即ER(-)/PR(+)组179 例,ER(-)/PR(-)组300 例,ER(+)/PR(+)组283 例。 分析3 组患者的年龄、月经状态、肿瘤大小、组织学分级、脉管侵犯、淋巴结状态、HER-2 状态及组织学类型等临床指标。 其中,年龄、月经状态、脉管侵犯、HER-2 状态和组织学类型等计数资料比较,采用χ2 检验,组间两两比较采用χ2 分割法;肿瘤大小、组织学分级等级资料比较,采用Kruskal-Wallis H 检验。 并用Kaplan-Meier 法进行生存分析,用Log-rank 法进行组间比较。

结果

ER(-)/PR(+)组、ER(-)/ PR(-)组及ER(+)/PR(+)组中,发病年龄＜50 岁者分别占56.4%(101/179),62.7%(188/300)和35.0%(99/283),3 组相比,差异有统计学意义(χ2 =47.497,P＜0.001),其中,ER(-)/PR(+)组患者发病年龄比ER(+)/PR(+)组患者明显年轻(χ2 =20.535,P ＜0.017),而与ER(-)/PR(-) 组相比,差异无统计学意义(χ2=1.825,P＞0.017);并且,3 组肿瘤组织学分级差异也有统计学意义(χ2=30.362,P＜0.001),其中,ER(-)/PR(+)组肿瘤的组织学分级比ER(+)/PR(+)组高(P=0.017),而与ER(-)/PR(-)组相比,差异无统计学意义(P=0.126);3 组间HER-2 阳性表达差异也有统计学意义(χ2=56.518,P＜0.001),其中,ER(-)/PR(+)组HER-2 阳性比例明显高于ER(-)/PR(-)组和ER(+)/PR(+)组(χ2 =6.298、51.044,P 均＜0.017)。 中位随访62 个月(17 ～94 个月),ER(-)/PR(+)组、ER(-)/PR(-)组及ER(+)/PR(+)组患者5 年DFS 率分别为44%、40%和74%,5 年OS 率分别为87%、77%和95%,3 组相比,差异均有统计学意义(5 年DFS 率比较,χ2=95.269,P＜0.001;5 年OS 率比较,χ2 =45.768,P＜0.001),其中,ER(-)/PR(+)组5 年DFS 率和OS 率均低于ER(+)/PR(+)组(χ2=56.276,P＜0.001;χ2=17.454,P＜0.001),而与ER(-)/PR(-)组相比,5 年DFS 率的差异无统计学意义(χ2 =3.010,P=0.083),5 年OS 率高于ER(-)/PR(-)组(χ2 =5.549,P=0.018)。

结论

ER(-)/PR(+)乳腺癌具有发病年龄早、组织学分级高、HER-2 阳性率高等特点,与ER(+)/PR(+)乳腺癌相比有更强的侵袭性和更差的预后,临床病理特征及预后与ER(-)/PR(-)乳腺癌更类似,值得深入探索。

关键词: 乳腺肿瘤, 受体, 雌激素, 受体, 孕酮, 免疫组织化学

Objective

To investigate the clinicopathological characteristics of ER(-)/PR(+) breast cancer and patients'prognosis.

Methods

We retrospectively analyzed the clinicopathological data of 762 breast cancer patients in the Affiliated Cancer Hospital of Zhengzhou University between January 2005 and December 2008. According to their ER and PR status, they were divided into three groups: ER(-)/PR(+) group (n=179), ER(-)/PR(-) group (n = 300), and ER(+)/PR(+) group (n = 283). Clinicopathological parameters including age, menstruation, tumor size, histological grade, lymphatic or vascular invasion, lymph node status, HER-2 status and histological grade were evaluated. The numeration data including age,menstruation, lymphatic or vascular invasion, HER-2 status and histological type were compared among groups using χ2 test, Pairwise comparison was conducted using χ2 segmentation. The ranked data including tumor size and histological grade were compared using Kruskal-Wallis H test. Kaplan-Meier method was used for survival analysis and log-rank test was used for group comparison.

Results

The proportion of the patients＜50 years was 56.4%(101/179)in ER(-)/PR(+) group, 62.7%(188/300)in ER(-)/PR(-)group and 35.0%(99/283)in ER(+)/PR(+) group, indicating a significant difference (χ2=47.497, P＜0.001). The onset age in ER(-)/PR(+) group were significantly younger than that in ER(+)/PR(+) group (χ2=20.535,P＜0.017) while there was no significant difference between ER(-)/PR(-) group and ER(-)/PR(+)group(χ2=1.825,P＞0.017). There was a significant difference in histological grade among three groups(χ2 =30.362,P＜0.001). ER(-)/PR(+) group had a higher histological grade compared with ER(+)/PR(+)group (P=0.017) while no significant difference was found between ER(-)/PR(+) group and ER(-)/PR(-)group (P=0.126).There was a significant difference in HER-2 expression among three groups (χ2=56.518,P＜0.001),and HER-2 positive rate in ER(-)/PR(+) group was significantly higher than that in the other two groups(χ2=6.298,51.044,both P＜0.017). The patients were followed up for median 62 months (17-94 months). The 5-year DFS was 44%,40% and 74% in ER(-)/PR(+) group, ER(-)/PR(-)group and ER(+)/PR(+) group, respectively, and the 5-year OS was 87%, 77% and 95% in ER(-)/PR(+) group,ER(-)/PR(-)group and ER(+)/PR(+) group, respectively. The 5-year DFS and OS both presented significant differences (the 5-year DFS:χ2=95.269, P＜0.001; the 5-year OS: χ2=45.768, P＜0.001). The 5-year DFS and OS in ER(-)/PR(+) group were significantly lower than those in ER(+)/PR(+) group(χ2=56.276, P＜0.001; χ2 =17.454, P＜0.001), while no significant difference was noted in the 5-year DFS between ER(-)/PR(+) group and ER(-)/PR(-) group (χ2=3.010,P=0.083), and the 5-year OS in ER(-)/PR(+) group was higher than that in ER(-)/PR(-) group(χ2 = 5.549, P = 0.018).

Conclusions

ER(-)/PR(+) breast cancer has young age of onset,advanced histological grade and high rate of HER-2 positive. It has clinicopathological characteristics and prognosis similar to ER(-)/PR(-) tumor,but stronger invasion and worse prognosis compared with ER(+)/PR(+) tumor, which requires further research.

Key words: Breast neoplasms, Receptors, estrogen, Receptors, progesterone, Immunohistochemistry
图1 乳腺癌组织中雌激素受体免疫组织化学染色阴性(HE ×200) 注:＜1%肿瘤细胞核染色阳性
图2 乳腺癌组织中孕激素受体免疫组织化学染色阳性(HE ×200) 注:70%肿瘤细胞核染色阳性
表1 ER(-)/PR(+)组、ER(-)/PR(-)组和ER(+)/PR(+)组乳腺癌患者的临床病理特征[例(%)]
组别 例数 年龄 月经状态 肿瘤大小 组织学分级c
＜50岁 ≥50岁 绝经前 绝经后 T1 T2 T3 Ⅰ Ⅱ Ⅲ
ER(-)/PR(+)组 179 101(56.4)a 78(43.6) 95(53.1)b 84(46.9) 42(23.5) 97(54.2) 40(22.3) 19(10.6) 81(45.3) 79(44.1)
ER(-)/PR(-)组 300 188(62.7) 112(37.3) 186(62.0) 114(38.0) 65(21.7) 176(58.7) 59(19.6) 14(4.7) 133(44.3) 153(51.0)
ER(+)/PR(+)组 283 99(35.0) 184(65.0) 124(43.8) 159(56.2) 86(30.4) 149(52.6) 48(17.0) 23(8.2) 181(63.9) 79(27.9)
χ2值 47.497 19.338 5.685f 30.362f
P值 ＜0.001 ＜0.001 0.058 ＜0.001
组别 例数 脉管侵犯 淋巴结状态 HER-2状态 组织学类型
有 无 阴性 阳性 阳性 阴性 浸润性导管癌 其他类型g
ER(-)/PR(+)组 179 39(21.8)d 140(78.2) 98(54.7) 81(45.3) 117(65.4)e 62(34.6) 147(82.1) 32(17.9)
ER(-)/PR(-)组 300 86(28.7) 214(71.3) 163(54.3) 137(45.7) 161(53.7) 139(46.3) 257(85.7) 43(14.3)
ER(+)/PR(+)组 283 55(19.4) 228(80.6) 174(61.5) 109(38.5) 89(31.4) 194(68.46) 227(80.2) 56(19.8)
χ2值 7.316 3.562 56.518 3.121
P值 0.026 0.168 ＜0.001 0.210
图3 3 组乳腺癌患者的无瘤生存曲线比较 注:3 组比较, χ2=95.269,P＜0.001
图4 3 组乳腺癌患者的总生存曲线比较 注:3 组比较,χ2=45.768,P＜0.001
[1]
Thike AA, Chng MJ, Fook-Chong S, et al. Immunohistochemical expression of hormone receptors in invasive breast carcinoma:correlation of results of H-score with pathological parameters [J].Pathology,2001,33(1):21-25.
[2]
Grann VR, Troxel AB, Zojwalla NJ, et al. Hormone receptor status and survival in a population-based cohort of patients with breast carcinoma[J]. Cancer,2005,103(11):2241-2251.
[3]
Rakha EA, El-Sayed ME, Green AR, et al. Biologic and clinical characteristics of breast cancer with single hormone receptor-positive phenotype[J]. J Clin Oncol,2007,25(30):4772-4778.
[4]
Perou CM. Molecular stratification of triple-negative breast cancers[J].Oncologist,2011,16 Suppl 1:61-70.
[5]
Fisher B, Redmond C, Fisher ER, et al. Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from National Surgical Adjuvant Breast and Bowel Project Protocol B-06[J]. J Clin Oncol,1988,6(7):1076-1087.
[6]
Carlson RW, McCormick B. Update: NCCN breast cancer clinical practice guidelines[J]. J Nat Compr Canc Netw, 2005, 3 Suppl 1:S7-11.
[7]
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer.I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up [J]. Histopathology, 1991,19(5):403-410.
[8]
Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version)[J]. Arch Pathol Lab Med,2010,134(7): e48-72.
[9]
江泽飞,邵志敏, 徐兵河. 人表皮生长因子受体2 阳性乳腺癌临床诊疗专家共识[J]. 中华肿瘤杂志,2010,32(2):158-160.
[10]
Rhodes A, Jasani B, Balaton AJ, et al. Frequency of oestrogen and progesterone receptor positivity by immunohistochemical analysis in 7016 breast carcinomas: correlation with patient age, assay sensitivity,threshold value, and mammographic screening[J]. J Clin Pathol,2000,53(9):688-696.
[11]
Ahmed SS, Thike AA, Zhang K, et al. Clinicopathological characteristics of oestrogen receptor negative, progesterone receptor positive breast cancers: re-evaluating subsets within this group[J]. J Clin Pathol,2017,70(4):320-326.
[12]
RhodesA, Jasani B. The oestrogen receptor-negative/progesterone receptor-positive breast tumour: a biological entity or a technical artefact? [J]. J Clin Pathol,2009,62(1):95-96.
[13]
Bardou VJ, Arpino G, Elledge RM, et al. Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases[J]. J Clin Oncol,2003,21(10):1973-1979.
[14]
Yu KD, Wu J, Shen ZZ, et al. Hazard of breast cancer-specific mortality among women with estrogen receptor-positive breast cancer after five years from diagnosis: implication for extended endocrine therapy[J]. J Clin Endocrinol Metab,2012,97(12): E2201-2209.
[15]
Liu S, Chia SK, Mehl E, et al. Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients[J]. Breast Cancer Res Treat, 2010,119(1):53-61.
[16]
Brisken C. Progesterone signalling in breast cancer: a neglected hormone coming into the limelight [J]. Nat Rev Cancer, 2013,13(6):385-396.
[17]
Prat A, Cheang MC, Martín M, et al. Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer[J]. J Clinl Oncol, 2013,31(2):203-209.
[18]
Cui X, Schiff R,Arpino G,et al. Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy[J]. J Clin Oncol,2005,23(30):7721-7735.
[19]
Fuqua SA,Cui Y,Lee AV,et al. Insights into the role of progesterone receptors in breast cancer[J]. J Clin Oncol,2005,23(4):931-932.
[20]
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Davies C, Godwin J,et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level metaanalysis of randomised trials [J]. Lancet, 2011, 378 (9793):771-784.
[21]
Dunnwald LK, Rossing MA, Li CI. Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients[J]. Breast Cancer Res,2007,9(1): R6.
[22]
Shen T, Brandwein-Gensler M, Hameed O, et al. Characterization of estrogen receptor-negative/progesterone receptor-positive breast cancer[J]. Human Pathol,2015,46(11):1776-1784.
[23]
Dowsett M. Overexpression of HER-2 as a resistance mechanism to hormonal therapy for breast cancer [J]. Endocr Relat Cancer, 2001,8(3):191-195.
[1] 李洋, 蔡金玉, 党晓智, 常婉英, 巨艳, 高毅, 宋宏萍. 基于深度学习的乳腺超声应变弹性图像生成模型的应用研究[J/OL]. 中华医学超声杂志（电子版）, 2024, 21(06): 563-570.
[2] 周荷妹, 金杰, 叶建东, 夏之一, 王进进, 丁宁. 罕见成人肋骨郎格汉斯细胞组织细胞增生症被误诊为乳腺癌术后骨转移一例[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 380-383.
[3] 河北省抗癌协会乳腺癌专业委员会护理协作组. 乳腺癌中心静脉通路护理管理专家共识[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 321-329.
[4] 刘晨鹭, 刘洁, 张帆, 严彩英, 陈倩, 陈双庆. 增强MRI 影像组学特征生境分析在预测乳腺癌HER-2 表达状态中的应用[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 339-345.
[5] 张晓宇, 殷雨来, 张银旭. 阿帕替尼联合新辅助化疗对三阴性乳腺癌的疗效及预后分析[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 346-352.
[6] 邱琳, 刘锦辉, 组木热提·吐尔洪, 马悦心, 冷晓玲. 超声影像组学对致密型乳腺背景中非肿块型乳腺癌的诊断价值[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 353-360.
[7] 程燕妮, 樊菁, 肖瑶, 舒瑞, 明昊, 党晓智, 宋宏萍. 乳腺组织定位标记夹的应用与进展[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 361-365.
[8] 韩萌萌, 冯雪园, 马宁. 乳腺癌改良根治术后桡神经损伤1例[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 117-118.
[9] 高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[10] 张志兆, 王睿, 郜苹苹, 王成方, 王成, 齐晓伟. DNMT3B与乳腺癌预后的关系及其生物学机制[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 624-629.
[11] 王玲艳, 高春晖, 冯雪园, 崔鑫淼, 刘欢, 赵文明, 张金库. 循环肿瘤细胞在乳腺癌新辅助及术后辅助治疗中的应用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 630-633.
[12] 赵林娟, 吕婕, 王文胜, 马德茂, 侯涛. 超声引导下染色剂标记切缘的梭柱型和圆柱型保乳区段切除术的效果研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 634-637.
[13] 刘先勇, 秦东梅, 张若梅, 李俊娇, 孟春芹, 邬明歆, 王玉红, 赵新鲜, 徐瑞联, 洪文文, 马玲, 仇玮, 周宇. Her2/Hes1在肠型胃癌Correa级联反应3个病理阶段中的表达及意义[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 321-327.
[14] 陈伟杰, 何小东. 胆囊癌免疫靶向治疗进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 763-768.
[15] 谭瑞义. 小细胞骨肉瘤诊断及治疗研究现状与进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(08): 781-784.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号