三阴性乳腺癌的临床病理特征及预后的研究
摘要
目的通过回顾性分析研究三阴性乳腺癌的临床病理特点和复发转移生存情况,以期探讨三阴性乳腺癌的临床特点及预后情况。
方法本文回顾性研究分析乳腺癌患者295例,其中三阴性乳腺癌45例,非三阴性乳腺癌250例,采用Cox多元回归分析及Kaplan—Meier法和卡方检验等统计学方法进行分析。
结果三阴性乳腺癌占同期乳腺癌患者的15%,与同期非三阴乳腺癌比较,三阴乳腺癌患者诊断时肿瘤直径大,分期较晚,腋窝淋巴结转移率高,p53突变率高以及复发转移率高,转移部位以内脏及脑多见。与非三阴性乳腺癌比较,三阴组5年生存率及5年无疾病进展生存率较差(71.1%V84%,p=0.038<0.05;48.9%V73.2%,p=0.001<0.05)。单因素分析结果显示:三阴乳腺癌患者的预后与原发肿瘤直径大,分期较晚,淋巴结转移率高及p53突变有关。多因素分析显示:淋巴结转移情况和p53突变是影响三阴乳腺癌预后的独立因素。
结论与非三阴乳腺癌比较:三阴乳腺癌具有就诊时肿瘤直径大,分期晚,腋窝淋巴结转移率高,p53突变率高等特点,三阴乳腺癌5年总生存率、5年无疾病进展生存率较差,复发转移率高,转移部位以内脏及脑多见。
Objective The aim of this study was to analyze the Clinicalpathol- ogic charcteristics, metastasis, survival and Prognostic factors of Triple-negative breast cancer.
Methods Clinicapathologic data of 295 patients , and 45 patients were Triple-negative breast cancer. The Clinicapathologic Charcteristics, recurrence and survival of the patients were Analyzed.
Results 15% all of breast cancers was TNBC. Compared to The non-TNBC, TNBC had larger tumor size ,advanced pathologic stage, more lymph node metastasis at diagnosis, higher mutation rate of p53 and recurrence rate. The 5-year disease free survival (DFS)and overall survival of TNBC were 48.9% and 71.1%, respetively. Simple fator analysis showed that tumor size ,lymph node status, pathologic stage and the mutation of p53 were found to be correlated with OS. Multivariate cox regression showed that lymph node status and the mutation of p53 were the independent fators influencing the prognosis of TNBC.
Conclusion TNBC was characteristic of larger tumor size, more lymph node metastasis at diagnosis, advanced pathologic stage, higher mutation rate of p53 and recurrence rate, shorter survival time compared to the non-TNBC . The lymph node status and the mutation of p53 were the independent fators influencing the prognosis of TNBC.
方法本文回顾性研究分析乳腺癌患者295例,其中三阴性乳腺癌45例,非三阴性乳腺癌250例,采用Cox多元回归分析及Kaplan—Meier法和卡方检验等统计学方法进行分析。
结果三阴性乳腺癌占同期乳腺癌患者的15%,与同期非三阴乳腺癌比较,三阴乳腺癌患者诊断时肿瘤直径大,分期较晚,腋窝淋巴结转移率高,p53突变率高以及复发转移率高,转移部位以内脏及脑多见。与非三阴性乳腺癌比较,三阴组5年生存率及5年无疾病进展生存率较差(71.1%V84%,p=0.038<0.05;48.9%V73.2%,p=0.001<0.05)。单因素分析结果显示:三阴乳腺癌患者的预后与原发肿瘤直径大,分期较晚,淋巴结转移率高及p53突变有关。多因素分析显示:淋巴结转移情况和p53突变是影响三阴乳腺癌预后的独立因素。
结论与非三阴乳腺癌比较:三阴乳腺癌具有就诊时肿瘤直径大,分期晚,腋窝淋巴结转移率高,p53突变率高等特点,三阴乳腺癌5年总生存率、5年无疾病进展生存率较差,复发转移率高,转移部位以内脏及脑多见。
Objective The aim of this study was to analyze the Clinicalpathol- ogic charcteristics, metastasis, survival and Prognostic factors of Triple-negative breast cancer.
Methods Clinicapathologic data of 295 patients , and 45 patients were Triple-negative breast cancer. The Clinicapathologic Charcteristics, recurrence and survival of the patients were Analyzed.
Results 15% all of breast cancers was TNBC. Compared to The non-TNBC, TNBC had larger tumor size ,advanced pathologic stage, more lymph node metastasis at diagnosis, higher mutation rate of p53 and recurrence rate. The 5-year disease free survival (DFS)and overall survival of TNBC were 48.9% and 71.1%, respetively. Simple fator analysis showed that tumor size ,lymph node status, pathologic stage and the mutation of p53 were found to be correlated with OS. Multivariate cox regression showed that lymph node status and the mutation of p53 were the independent fators influencing the prognosis of TNBC.
Conclusion TNBC was characteristic of larger tumor size, more lymph node metastasis at diagnosis, advanced pathologic stage, higher mutation rate of p53 and recurrence rate, shorter survival time compared to the non-TNBC . The lymph node status and the mutation of p53 were the independent fators influencing the prognosis of TNBC.
引文
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[4]Gerson R,Alban F,Villalobos A,et al.Recurrence and survival rates among early breast cancer cases with triple negative immunophenotype[J].Gac Med Mex,2008,144(1): 27-34.
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[12]罗忠兵,龙浩,马国伟等.140例三阴乳腺癌病例分析.赣南医学院学报,2009,29(3):332-335.
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[21]Anders CK, Carey LA. Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer [J]. Clin Breast Cancer,2009,9 Suppl2: S73-S81.
[22]袁忠玉,王树森,高岩,等,305例三阴乳腺癌患者的临床特征及预后因素分析.《癌症》.2008,27(6):561-565
[23]李少林,任国胜,陈晓晶,等.乳腺癌的基础理论和临床实践.北京:科学出版社,2008
[24]Huang J,Tan PH,Thiyagarajan J,et a1.Glutathion S-transforase-pi in invasive breast cancer.Mod Pathol, 2003,16:558-565.
[25]Helen H,Chen W,Su W C,et a1.p53 and cerbB-2 but not bcl-2 are predictive of metastasis-flee survival in breast ca- ncer patients receiving post-mastectomy adjuvant radiot- herapy in Taiwan [J].Jpn J Clin Oncol,2002,32(9)332-339.
[26]李惠平,贾廷珍等.p53过表达可作为中国乳腺癌妇女的独立预后危险因素[A].2005上海国际乳腺癌暨第八届全国乳腺癌会议论文汇编[c].2005:60.
[27]杜长征,李惠平,马力文,等.中国乳腺癌患者p53基因表达临床生物学意义的Meta分析.《中国癌症杂志》.2005,15(6):514-517
[28]Kandioler-Eckersberger D,Ludwig C,Rudas M et a1.The P53mutation and p53 over expression for prediction of response toneoadjuvant treatment in breast cancer pati- ents[J].Clin Cancer Res,2000,6(1):50—56.
[29]Sarioglu S,Sokmen S,Terzi C,etal.Relationship of angi- ogenesis and p53 protein expression in colorectal car- cinomas. Colorectal Dis 2001;3(1):38-41
[30]何旭,张海英,张丽红等.乳腺癌生物学行为和预后判定微血管密度与p53蛋白的价值.《中国临床康复》.2004,8(5):900-901
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[4] West H, Franklin WA, McCoy J, et al.Gefitinib therapy in advanced bronchioloalveolar carcinoma: Southwest oncology groupstadys0126 [J].Clin Oncol 2006, 24(12) : 1807-1811
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[6]苏丽娅岳秀兰曹虹然白雪峰.散发性乳腺癌中BRCA1基因突变的探讨.中国肿瘤临床1000—8179(2007)05—0289-0293
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[2]Sorlie T,Perou C M,Tibshirani R,et a1.Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications[J].PNAS,2001,98 :10869—10874 .
[3]蔡铭泉,陈强,施纯枚,等.受体三阴性乳腺癌的研究进展[J] .临床肿瘤学杂志,2009,14(3) :283—287.
[4]Gerson R,Alban F,Villalobos A,et al.Recurrence and survival rates among early breast cancer cases with triple negative immunophenotype[J].Gac Med Mex,2008,144(1): 27-34.
[5]ComenEA,Davidsm,KirchhoffT,etal.Prevalence of BRCA1 and BRCA2 motations in Jewishwomen with triple negative breast cancer[J] Jclin Oncol 2008.26(15suppl):22002
[6]Sara M,Bando Y,Takahashi M,et a1.Screening for basal marker expression is necessary for decision of therapeutic strategy for triple—negative breast cancer [J].Surg Oncol,2008 ,97(1):30
[7]Kim MJ,Ro JY, Ahn SH,et a1. Clinicopatholo c significanceof the basal-like subtype of breast cancer comparison with hormone receptor and Her2 /neu—over expressing phen- otypes[J] .HumPathol,2OO6 ,37(9):1217
[8]Rakha EA,E1一Sayed ME,Green AR,et a1.Prognostic ma- rkers in triple—negative breast cancer[J].Cancer,2007, 109(1):25—32.
[9]Carey LA ,Dees EC,Sawyer I ,et a1.The triple nega—tive paradox:primary tumor chemosensitivity of breast cancer subtypes [J].Clin Cancer Res,2007,13(8):2329—2334.
[10]Bauer KR,Brown M,Cress RD,et a1.Descriptive analysis of estrogen receptor(ER)一negative,progesterone recept- or(PR)一negative,and HER2一negative invasive breast ca- ncer,the so called triple-negative phenotype:a population—based study from the California cancer Registry [J]. Cancer, 2007;109 (9 ): 1721.
[11]杨名添,戎铁华,黄植蕃,等.可手术乳腺癌6263例临床分析[J].癌症,2005,24(3):327—331.
[12]罗忠兵,龙浩,马国伟等.140例三阴乳腺癌病例分析.赣南医学院学报,2009,29(3):332-335.
[13]陆光明,李宇清,梅开勇等.CerbB-2、p53、Ki-67、ER、PR在乳腺癌中的表达及临床意义.国际医药卫生导报,2008,14(23):10-13.
[14] xu L,sgroi D,Sterner CJ ,et a1.Mutational analysis 0f CDKN2 (MTSl/P16 ink4)in human breast carcinomas[J].Cancer Res,1994,54:5262—5264.
[15]Brenner AJ,Aldaz CM.Chromosome 9P allelic loss and P16/CDKN2 in breast cancer and evidence 0f P16 inactivation in immortal breast epithelial cells[J].Cancer Res,1995.2892—2895.
[16] Quesnel B,Fenaux P,Phippe N,et a1.Analysis 0f P16 Gene detection and point mutation in breast carcinomas [J].Br J cancer,1995,72(2) :351—353.
[17]高学硕,万文徽,赵爱莲,等.P16蛋白在乳腺癌中表达状况及生物学意义[ J ].实用肿瘤杂志,2000,15(2):93—94.
[18]曹荣华,袁宏银.乳腺癌预后的影响因素分析.郧阳医学院学报(J YMC),2002,21(4):207-209.
[19] Nielsen T O,Hsu F D,Jensen K,et a1.Immunohistochemic- al and clinical characterization of the basa1-1ike subtype of invasive breast carcinoma [J] .Clin Cancer Res,2004,10: 5367—5374.
[20] Bauer KR, Brown M, Cress RD,eta1.Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer,the so-called triple-negative phenotype:a population -based study from the California cancer Registry [J]. Cancer, 2007, 109(9): l721-1728.
[21]Anders CK, Carey LA. Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer [J]. Clin Breast Cancer,2009,9 Suppl2: S73-S81.
[22]袁忠玉,王树森,高岩,等,305例三阴乳腺癌患者的临床特征及预后因素分析.《癌症》.2008,27(6):561-565
[23]李少林,任国胜,陈晓晶,等.乳腺癌的基础理论和临床实践.北京:科学出版社,2008
[24]Huang J,Tan PH,Thiyagarajan J,et a1.Glutathion S-transforase-pi in invasive breast cancer.Mod Pathol, 2003,16:558-565.
[25]Helen H,Chen W,Su W C,et a1.p53 and cerbB-2 but not bcl-2 are predictive of metastasis-flee survival in breast ca- ncer patients receiving post-mastectomy adjuvant radiot- herapy in Taiwan [J].Jpn J Clin Oncol,2002,32(9)332-339.
[26]李惠平,贾廷珍等.p53过表达可作为中国乳腺癌妇女的独立预后危险因素[A].2005上海国际乳腺癌暨第八届全国乳腺癌会议论文汇编[c].2005:60.
[27]杜长征,李惠平,马力文,等.中国乳腺癌患者p53基因表达临床生物学意义的Meta分析.《中国癌症杂志》.2005,15(6):514-517
[28]Kandioler-Eckersberger D,Ludwig C,Rudas M et a1.The P53mutation and p53 over expression for prediction of response toneoadjuvant treatment in breast cancer pati- ents[J].Clin Cancer Res,2000,6(1):50—56.
[29]Sarioglu S,Sokmen S,Terzi C,etal.Relationship of angi- ogenesis and p53 protein expression in colorectal car- cinomas. Colorectal Dis 2001;3(1):38-41
[30]何旭,张海英,张丽红等.乳腺癌生物学行为和预后判定微血管密度与p53蛋白的价值.《中国临床康复》.2004,8(5):900-901
[1] Sasa M,Bando Y,Takahashi M,et a1.Screening for basal marker expression is necessary for decision of therapeutic strategy for triple—negative breast cancer[J].J Surg Oncol,2008;97(1):30-33
[2] Rakha EA,E1-Sayed ME,Green AR,et a1.Prognostic markers in triple-negative breast cancer[J].Cancer,2007;109(1):25-29
[3] Siziopikou KP,Cobleigh M.The basal subtype of breast carcinomas may represent the group of breast tumors that could benefit from EGFR—targeted therapies[J].Breast,2007;16(1):1O4-109
[4] West H, Franklin WA, McCoy J, et al.Gefitinib therapy in advanced bronchioloalveolar carcinoma: Southwest oncology groupstadys0126 [J].Clin Oncol 2006, 24(12) : 1807-1811
[5] Turner N, Tutt A, A shwonh, A Hallmarks of BRCA1 in spora- dic cancers[J] NatRev Cancer,2004,4(2): 814-817
[6]苏丽娅岳秀兰曹虹然白雪峰.散发性乳腺癌中BRCA1基因突变的探讨.中国肿瘤临床1000—8179(2007)05—0289-0293
[7]Thike A A,Cheok P Y,JaraLazaro A R,et a1.Triple—negative breast cancer:clinicopathological characteristics andrelationship with basal—like breast cancer.ModPathol,2010,23:123—133
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