乳腺癌肝转移患者的临床病理特征及预后因素分析:基于SEER数据库的回顾性研究
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摘要
目的分析乳腺癌肝转移患者的临床特征,探讨影响乳腺癌肝转移患者预后的危险因素。方法收集美国国立癌症研究所监测、流行病学和结果数据库(SEER)中2010—2013年的3 468例初诊时发生器官转移的Ⅳ期乳腺癌患者的临床资料。根据是否发生肝转移分为肝转移组(1 001例)和非肝转移组(2 467例),通过χ~2检验和二元Logistic回归方法比较2组各临床病理特征的差异。选取其中随访资料齐全的肝转移患者930例,采用Kaplan-Meier法计算肝转移组的OS,采用Log-rank法分析各因素对生存率的影响。将单因素分析差异有统计学意义的变量纳入多因素Cox回归模型进行分析,得到影响乳腺癌肝转移者生存情况的独立危险因素。结果肝转移组与非肝转移组比较,以下临床病理特征差异有统计学意义:诊断年龄(χ~2=25.543,P<0.001)、人种(χ~2=8.516,P=0.014)、组织学分级(χ~2=55.474,P<0.001)、病理类型(χ~2=18.182,P<0.001)、原发侧(χ~2=4.851,P=0.028)、ER(χ~2=96.440,P<0.001)、PR(χ~2=105.707,P<0.001)及HER-2表达(χ~2=148.941,P<0.001)。二元Logistic回归结果显示,诊断年龄(OR=0.718,95%CI:0.605~0.851,P<0.001)、组织学分级(OR=1.156,95%CI:1.007~1.326,P=0.039)、ER(OR=0.712,95%CI:0.574~0.885,P=0.002)、PR(OR=0.681,95%CI:0.557~0.834,P<0.001)及HER-2(OR=2.167,95%CI:1.835~2.558,P<0.001)分别为影响肝转移发生的独立相关因素。930例患者中位生存时间为23个月,1年OS率为64.9%,3年OS率为34.2%。单因素生存分析显示:诊断年龄(χ~2=53.968,P<0.001)、人种(χ~2=9.677,P=0.008)、组织学分级(χ~2=6.826,P=0.033)、T分期(χ~2=10.467,P=0.016)、N分期(χ~2=18.057,P<0.001)、原发灶手术(χ~2=19.719,P<0.001)、原发灶放射治疗(χ~2=11.873,P=0.003)、其他器官转移(χ~2=12.262,P<0.001)、ER(χ~2=28.045,P<0.001)、PR(χ~2=40.418,P<0.001)及HER-2表达(χ~2=23.844,P<0.001)与患者OS有关。Cox回归分析结果显示:诊断年龄(HR=1.544,95%CI:1.353~1.762,P<0.001)、组织学分级(HR=1.249,95%CI:1.038~1.503,P=0.018)、T分期(HR=1.103,95%CI:1.004~1.211,P=0.042)、原发灶手术情况(HR=0.565,95%CI:0.457~0.700,P<0.001)、ER(HR=0.749,95%CI:0.586~0.958,P=0.022)、PR(HR=0.586,95%CI:0.453~0.759,P<0.001)及HER-2表达(HR=0.517,95%CI:0.418~0.640,P<0.001)是乳腺癌肝转移患者预后的独立影响因素。结论乳腺癌肝转移的发生风险可能与肿瘤组织的恶性程度有关。发生肝转移患者整体预后较差,诊断年龄较小、组织学分级较低、T分期较低、ER阳性、PR阳性及HER-2阳性的患者远期预后较好,对原发灶进行手术治疗可以显著改善患者预后。
Objective To investigate the clinical characteristics of breast cancer patients with liver metastasis and the risk factors on prognosis. Methods The clinical data of 3 468 de novo stage Ⅳ breast cancer patients with organ metastasis in the Surveillance,Epidemiology,and End Results( SEER) database of National Cancer Institute of the USA from 2010 to 2013 were analyzed. Patients were divided into liver metastasis group( n = 1 001) and non-liver metastasis group( n = 2 467). χ~2 test and binary Logistic regression were used to compare the clinical characteristics between two groups. There were 930 liver metastasis patients with complete follow-up data for sub-analysis. The Kaplan-Meier method was used to calculate the OS in patients with liver metastasis,and the effect of various factors on the survival rate was analyzed by Log-rank method. The significant factors in univariate analysis were included in the multivariate Cox regression model to screen out the independent risk factors. Results The following clinical characteristics presented a significant difference between liver metastasis group and non-liver metastasis group: age at diagnosis,race,histological grade,pathological type,primary side,ER,PR and HER-2 expression( χ~2= 25. 543,8. 516,55. 474,18. 182,4. 851,96. 440,105. 707,148. 941; all P < 0. 050). Binary Logistic regression results showed that age at diagnosis( OR = 0. 718,95%CI: 0. 605-0. 851,P< 0. 001),histological grade( OR = 1. 156,95% CI:1. 007-1. 326,P = 0. 039),ER( OR = 0. 712,95% CI: 0. 574-0. 885,P = 0. 002),PR( OR = 0. 681,95% CI:0. 557-0. 834,P< 0. 001) and HER-2( OR = 2. 167,95% CI: 1. 835-2. 558,P < 0. 001) were independent factors affecting liver metastasis. In 930 patients,the median survival was 23 months,the 1-year OS was64. 9% and 3-year OS was 34. 2%. The survival analysis showed that age at diagnosis( χ~2= 53. 968,P<0. 001),race( χ~2= 9. 677,P = 0. 008),histological grade( χ~2= 6. 826,P = 0. 033),T stage( χ~2= 10. 467,P = 0. 016),N stage( χ~2= 18. 057,P < 0. 001),surgery at primary lesions( χ~2= 19. 719,P < 0. 001),radiotherapy at primary lesions( χ~2= 11. 873,P = 0. 003),metastasis of other organs( χ~2= 12. 262,P <0. 001),ER( χ~2= 28. 045,P<0. 001),PR( χ~2= 40. 418,P<0. 001) and HER-2 expression( χ~2= 23. 844,P<0. 001) were significantly correlated with the patients' survival. Cox regression analysis showed that age at diagnosis( HR = 1. 544,95%CI: 1. 353-1. 762,P<0. 001),histological grade( HR = 1. 249,95%CI: 1. 038-1. 503,P = 0. 018),T stage( HR = 1. 103,95% CI: 1. 004-1. 211,P = 0. 042),surgery at primary lesions( HR= 0. 565,95%CI: 0. 457-0. 700,P<0. 001),ER( HR = 0. 749,95%CI: 0. 586-0. 958,P = 0. 022),PR( HR = 0. 586,95%CI: 0. 453-0. 759,P< 0. 001) and HER-2( HR = 0. 517,95% CI: 0. 418-0. 640,P <0. 001) were independent prognostic factors in breast cancer patients with liver metastasis. Conclusions The risk of liver metastasis in breast cancer may be correlated with malignancy of the tumor. The prognosis of breast cancer patients with liver metastasis is poor. The patients with younger age at diagnosis,lower histological grade and T stage,ER positive,PR positive and HER-2 positive have a better long-term prognosis. Surgical treatment for primary tumor can significantly improve the patients' prognosis.
Objective To investigate the clinical characteristics of breast cancer patients with liver metastasis and the risk factors on prognosis. Methods The clinical data of 3 468 de novo stage Ⅳ breast cancer patients with organ metastasis in the Surveillance,Epidemiology,and End Results( SEER) database of National Cancer Institute of the USA from 2010 to 2013 were analyzed. Patients were divided into liver metastasis group( n = 1 001) and non-liver metastasis group( n = 2 467). χ~2 test and binary Logistic regression were used to compare the clinical characteristics between two groups. There were 930 liver metastasis patients with complete follow-up data for sub-analysis. The Kaplan-Meier method was used to calculate the OS in patients with liver metastasis,and the effect of various factors on the survival rate was analyzed by Log-rank method. The significant factors in univariate analysis were included in the multivariate Cox regression model to screen out the independent risk factors. Results The following clinical characteristics presented a significant difference between liver metastasis group and non-liver metastasis group: age at diagnosis,race,histological grade,pathological type,primary side,ER,PR and HER-2 expression( χ~2= 25. 543,8. 516,55. 474,18. 182,4. 851,96. 440,105. 707,148. 941; all P < 0. 050). Binary Logistic regression results showed that age at diagnosis( OR = 0. 718,95%CI: 0. 605-0. 851,P< 0. 001),histological grade( OR = 1. 156,95% CI:1. 007-1. 326,P = 0. 039),ER( OR = 0. 712,95% CI: 0. 574-0. 885,P = 0. 002),PR( OR = 0. 681,95% CI:0. 557-0. 834,P< 0. 001) and HER-2( OR = 2. 167,95% CI: 1. 835-2. 558,P < 0. 001) were independent factors affecting liver metastasis. In 930 patients,the median survival was 23 months,the 1-year OS was64. 9% and 3-year OS was 34. 2%. The survival analysis showed that age at diagnosis( χ~2= 53. 968,P<0. 001),race( χ~2= 9. 677,P = 0. 008),histological grade( χ~2= 6. 826,P = 0. 033),T stage( χ~2= 10. 467,P = 0. 016),N stage( χ~2= 18. 057,P < 0. 001),surgery at primary lesions( χ~2= 19. 719,P < 0. 001),radiotherapy at primary lesions( χ~2= 11. 873,P = 0. 003),metastasis of other organs( χ~2= 12. 262,P <0. 001),ER( χ~2= 28. 045,P<0. 001),PR( χ~2= 40. 418,P<0. 001) and HER-2 expression( χ~2= 23. 844,P<0. 001) were significantly correlated with the patients' survival. Cox regression analysis showed that age at diagnosis( HR = 1. 544,95%CI: 1. 353-1. 762,P<0. 001),histological grade( HR = 1. 249,95%CI: 1. 038-1. 503,P = 0. 018),T stage( HR = 1. 103,95% CI: 1. 004-1. 211,P = 0. 042),surgery at primary lesions( HR= 0. 565,95%CI: 0. 457-0. 700,P<0. 001),ER( HR = 0. 749,95%CI: 0. 586-0. 958,P = 0. 022),PR( HR = 0. 586,95%CI: 0. 453-0. 759,P< 0. 001) and HER-2( HR = 0. 517,95% CI: 0. 418-0. 640,P <0. 001) were independent prognostic factors in breast cancer patients with liver metastasis. Conclusions The risk of liver metastasis in breast cancer may be correlated with malignancy of the tumor. The prognosis of breast cancer patients with liver metastasis is poor. The patients with younger age at diagnosis,lower histological grade and T stage,ER positive,PR positive and HER-2 positive have a better long-term prognosis. Surgical treatment for primary tumor can significantly improve the patients' prognosis.
引文
[1]Siegel RL,Miller KD,Jemal A.Cancer statistics,2017[J].CA Cancer J Clin,2017,67(1):7-30.
[2]Jung KW,Won YJ,Kong HJ,et al.Survival of korean adult cancer patients by stage at diagnosis,2006-2010:national cancer registry study[J].Cancer Res Treat,2013,45(3):162-171.
[3]Li J,Zhang BN,Fan JH,et al.A nation-wide multicenter 10-year(1999-2008)retrospective clinical epidemiological study of female breast cancer in China[J].BMC Cancer,2011,11:364.
[4]易平,刘剑勇,张志明,等.Luminal型乳腺癌术后肝转移患者预后因素分析[J].中华肿瘤防治杂志,2016,23(24):1619-1622.
[5]Wu SG,Li H,Tang LY,et al.The effect of distant metastases sites on survival in de novo stage-Ⅳbreast cancer:A SEER database analysis[J].Tumour Biol,2017,39(6):1010428317705082.
[6]Edge SB,Byrd DR,Compton CC,et al.AJCC cancer staging handbook[M].7th ed.New York:Springer-Verlag,2010.
[7]Schuetz F,Diel I,Pueschel M,et al.Reduced incidence of distant metastases and lower mortality in 1072 patients with breast cancer with a history of hormone replacement therapy[J].Am J Obstet Gynecol,2007,196(4):342.
[8]Ma R,Feng Y,Lin S,et al.Mechanisms involved in breast cancer liver metastasis[J].J Transl Med,2015,13:64.
[9]Soni A,Ren Z,Hameed O,et al.Breast cancer subtypes predispose the site of distant metastases[J].Am J Clin Pathol,2015,143(4):471-478.
[10]Beca F,Santos R,Vieira D,et al.Primary relapse site pattern in women with triple-negative breast cancer[J].Pathol Res Pract,2014,210(9):571-575.
[11]朱美琴,张东生,苏争艳,等.98例乳腺癌肝转移患者的回顾性研究分析[J].癌症,2007,26(4):423-426.
[12]王佳玉,徐兵河,田丽军,等.乳腺癌肝转移的临床病程与预后分析[J].中华肿瘤杂志,2006,28(8):612-616.
[13]尹预真,周菊英.乳腺癌术后肝转移34例相关性因素分析[J].南通医学院学报,2009,29(1):44-45.
[14]盛湲,李恒宇.从单细胞水平看肿瘤异质性[J/CD].中华乳腺病杂志(电子版),2014,8(6):6-12.
[15]贺洪洲,宋俊,吴斌.乳腺癌肝转移研究进展[J].中国普外基础与临床杂志,2017,24(7):905-911.
[16]白秀梅,杨薇,严昆.乳腺癌肝转移治疗现状及射频消融的应用及前景[J].世界华人消化杂志,2017,25(13):1143-1149.
[17]Rakha EA,El-Sayed ME,Lee AH,et al.Prognostic significance of Nottingham histologic grade in invasive breast carcinoma[J].J Clin Oncol,2008,26(19):3153-3158.
[18]Frkovic-Grazio S,Bracko M.Long term prognostic value of Nottingham histological grade and its components in early(p T1N0M0)breast carcinoma[J].J Clin Pathol,2002,55(2):88-92.
[19]Park S,Koh E,Koo JS,et al.Lack of both androgen receptor and forkhead box A1(FOXA1)expression is a poor prognostic factor in estrogen receptor-positive breast cancers[J].Oncotarget,2017,8(47):82 940-82 955.
[20]Gabos Z,Sinha R,Hanson J,et al.Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer[J].J Clin Oncol,2006,24(36):5658-5663.
[2]Jung KW,Won YJ,Kong HJ,et al.Survival of korean adult cancer patients by stage at diagnosis,2006-2010:national cancer registry study[J].Cancer Res Treat,2013,45(3):162-171.
[3]Li J,Zhang BN,Fan JH,et al.A nation-wide multicenter 10-year(1999-2008)retrospective clinical epidemiological study of female breast cancer in China[J].BMC Cancer,2011,11:364.
[4]易平,刘剑勇,张志明,等.Luminal型乳腺癌术后肝转移患者预后因素分析[J].中华肿瘤防治杂志,2016,23(24):1619-1622.
[5]Wu SG,Li H,Tang LY,et al.The effect of distant metastases sites on survival in de novo stage-Ⅳbreast cancer:A SEER database analysis[J].Tumour Biol,2017,39(6):1010428317705082.
[6]Edge SB,Byrd DR,Compton CC,et al.AJCC cancer staging handbook[M].7th ed.New York:Springer-Verlag,2010.
[7]Schuetz F,Diel I,Pueschel M,et al.Reduced incidence of distant metastases and lower mortality in 1072 patients with breast cancer with a history of hormone replacement therapy[J].Am J Obstet Gynecol,2007,196(4):342.
[8]Ma R,Feng Y,Lin S,et al.Mechanisms involved in breast cancer liver metastasis[J].J Transl Med,2015,13:64.
[9]Soni A,Ren Z,Hameed O,et al.Breast cancer subtypes predispose the site of distant metastases[J].Am J Clin Pathol,2015,143(4):471-478.
[10]Beca F,Santos R,Vieira D,et al.Primary relapse site pattern in women with triple-negative breast cancer[J].Pathol Res Pract,2014,210(9):571-575.
[11]朱美琴,张东生,苏争艳,等.98例乳腺癌肝转移患者的回顾性研究分析[J].癌症,2007,26(4):423-426.
[12]王佳玉,徐兵河,田丽军,等.乳腺癌肝转移的临床病程与预后分析[J].中华肿瘤杂志,2006,28(8):612-616.
[13]尹预真,周菊英.乳腺癌术后肝转移34例相关性因素分析[J].南通医学院学报,2009,29(1):44-45.
[14]盛湲,李恒宇.从单细胞水平看肿瘤异质性[J/CD].中华乳腺病杂志(电子版),2014,8(6):6-12.
[15]贺洪洲,宋俊,吴斌.乳腺癌肝转移研究进展[J].中国普外基础与临床杂志,2017,24(7):905-911.
[16]白秀梅,杨薇,严昆.乳腺癌肝转移治疗现状及射频消融的应用及前景[J].世界华人消化杂志,2017,25(13):1143-1149.
[17]Rakha EA,El-Sayed ME,Lee AH,et al.Prognostic significance of Nottingham histologic grade in invasive breast carcinoma[J].J Clin Oncol,2008,26(19):3153-3158.
[18]Frkovic-Grazio S,Bracko M.Long term prognostic value of Nottingham histological grade and its components in early(p T1N0M0)breast carcinoma[J].J Clin Pathol,2002,55(2):88-92.
[19]Park S,Koh E,Koo JS,et al.Lack of both androgen receptor and forkhead box A1(FOXA1)expression is a poor prognostic factor in estrogen receptor-positive breast cancers[J].Oncotarget,2017,8(47):82 940-82 955.
[20]Gabos Z,Sinha R,Hanson J,et al.Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer[J].J Clin Oncol,2006,24(36):5658-5663.