转录因子叉头框C1在三阴性乳腺癌中的表达及其与患者预后的关系

目的探讨转录因子叉头框C1(FOXC1)在三阴性乳腺癌(TNBC)中的表达及其与患者预后的关系。 方法回顾性分析2002年3月至2012年3月在中国医学科学院北京协和医学院北京协和医院进行乳腺癌改良根治术或保留乳房手术的TNBC患者临床资料。患者随访截止日期为2019年3月1日。选择符合纳入、排除标准且有复发、转移或随访10年以上无复发、转移的患者,提取乳腺癌原发灶组织RNA进行分析。排除标本不足或RNA提取质控不达标的患者后,最终有59例(27例无复发、转移,32例复发、转移)标本通过定量反转录聚合酶链反应(qRT-PCR)检测FOXC1表达量。患者临床特征的分析采用χ²检验或非参数检验(Mann-Witney U检验);复发、转移组与无复发、转移组患者年龄及FOXC1表达量(ΔCT值)的比较采用t检验;多因素分析采用Cox比例风险回归模型;患者生存率的比较采用log-rank检验。 结果复发、转移组与无复发、转移组患者比较,年龄、肿瘤大小、组织学分级、P53、Ki67表达和脉管癌栓的差异均无统计学意义(t＝－0.226,P＝0.165;χ²＝1.923,P＝0.165;Z＝－1.694,P＝0.090;χ²＝0.336,P＝0.562;P＝1.000;P＝1.000),但复发、转移组患者腋窝淋巴结转移的比例更高[75.0% (24/32)比40.7% (11/27),χ²＝7.123,P＝0.008]。复发、转移组FOXC1表达量是无复发、转移组的2.7倍,2组比较,差异有统计学意义(ΔCT值：4.064±1.392比5.510±1.581,t＝3.737,P<0.001)。多因素分析提示,FOXC1高表达是TNBC患者无复发生存(RFS)的独立危险因素(HR＝2.531,95%CI：1.211～5.290,P＝0.014),而临床上常用的病理指标,仅淋巴结转移与RFS相关(HR＝2.453,95%CI：1.093～5.504,P＝0.030)。FOXC1高表达的TNBC患者,其RFS和OS都更差(RFS：χ²＝8.419,P＝0.004;OS：χ²＝4.644,P＝0.031)。 结论FOXC1高表达患者出现复发、转移的风险显著增加,可以作为TNBC预后细分的有用指标。     

整合素β3在三阴性乳腺癌中的表达及其与预后的关系

摘 要：［目的］ 探讨整合素β3在三阴性乳腺癌中的临床意义。［方法］ 免疫组织化学染色法检测98例三阴性乳腺癌组织中整合素β3的表达情况。［结果］ 在三阴性乳腺癌患者中整合素β3表达与患者的绝经状态及淋巴结转移状态密切相关(P<0.05)。整合素β3阳性的三阴性乳腺癌患者的5年无病生存时间及乳腺癌特异性生存时间均显著差于整合素β3阴性者。Cox多因素分析显示整合素β3是三阴性乳腺癌预后不良的独立危险因素(HR=1.910,95%CI：1.069~3.413;P=0.029）。［结论］ 整合素β3可作为判断三阴性乳腺癌预后的重要指标及潜在的治疗靶点。     

ICAM-1在三阴性乳腺癌中的表达的临床意义及与预后的关系

背景与目的:三阴性乳腺癌(triple-negative breast cancer,TNBC)侵袭性强,预后差,治疗手段匮乏.该研究通过检测人TNBC与对应癌旁组织中细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)蛋白的表达,研究ICAM-1蛋白与TNBC临床病理特征及预后的相关性.方法:收集59例TNBC及其对应的50例癌旁组织标本,应用免疫组织化学法检测ICAM-1在59例TNBC及50例癌旁组织中的表达水平,比较其阳性率.分析ICAM-1蛋白的表达与TNBC年龄、肿瘤大小、临床病理类型、组织学分级、淋巴结转移、肿瘤TNM分期、脉管癌栓、神经浸润、Ki-67、p53和E-cadherin等临床病理特征及与患者预后的关系.结果:TNBC中ICAM-1的表达明显高于癌旁组织(P=0.000).ICAM-1与淋巴转移、组织学分级和TNM分期有关(P分别为0.036、0.027和0.048),与肿瘤大小、临床病理类型、脉管癌栓、Ki-67水平、p53和E-cadherin表达等无关.ICAM-1高表达组患者的无病生存时间(disease-free survival,DFS)显著较ICAM-1低表达组短(P=0.036),但对于总生存时间(overall survival,OS)没有显著影响.另外,Cox比例风险模型多因素分析,ICAM-1表达、淋巴结转移是影响DFS的独立危险因素(HR=3.2,95%CI:1.6-6.4,HR=2.7,95%CI:1.3-5.9,P均<0.05).结论:ICAM-1蛋白可以作为判断TNBC恶性程度的指标,ICAM-1高表达的三阴性乳腺癌临床预后差.     

核因子-κＢ在三阴性乳腺癌中的表达及其意义

目的　探讨核因子-κＢ（ＮＦ-κＢ）在三阴性乳腺癌组织中的表达及其与临床病理特征和预后的关系。方法　应用免疫组化法ＰＶ-６０００二步法检测１３７例三阴性乳腺癌和１３２例非三阴性乳腺癌患者癌组织ＮＦ-κＢ的表达,分析其与临床病理特征和预后之间的关系。结果　１３７例三阴性乳腺癌组织中的ＮＦ-κＢ阳性表达率为７３.７％（１０１／１３７）,明显高于非三阴性乳腺癌的４６.２％（６１／１３２）,差异有统计学意义（Ｐ＝０.０００）。在１３７例三阴性乳腺癌中,ＮＦ-κＢ表达与ＶＥＧＦ、ｐ５３、组织分级、淋巴结转移、５年无病生存率和５年总生存率有关（Ｐ＜０.０５）;而在１３２例非三阴性乳腺癌中,ＮＦ-κＢ表达仅与ＶＥＧＦ、淋巴结转移、５年无病生存率相关（Ｐ＜０.０5）。结论　ＮＦ-κＢ在三阴性乳腺癌中表达率高,并可作为三阴性乳腺癌的预后指标。     

凋亡抑制因子Livin在三阴性乳腺癌中的表达及其判断预后的价值

  目的  探讨凋亡抑制因子Livin在三阴性乳腺癌中的表达及与预后的关系, 分析三阴性乳腺癌的独立预后影响因素。   方法  用免疫组织化学SP法检测90例三阴性乳腺癌、35例癌旁乳腺组织、10例正常乳腺组织中Livin的表达; 结合临床病理特征和随访资料, 建立Cox模型进行回归分析。   结果   Livin在三阴性乳腺癌中的表达率为57.8%, 在癌旁乳腺组织中的表达率为34.3%, 在正常乳腺组织中表达率为0, 三者之间差异有统计学意义(P < 0.05)。Livin的表达与临床分期、脉管癌栓及腋淋巴结转移均有显著性差异(P < 0.05), 而与年龄、肿瘤大小、乳腺癌家族史及组织学分级无显著性差异(P > 0.05)。Kaplan-Meier生存曲线显示, Livin蛋白低表达组患者的无瘤生存时间及总生存时间明显优于Livin蛋白高表达组患者。多因素Cox回归分析显示, 年龄、临床分期、脉管癌栓及腋淋巴结转移情况是影响患者DFS的独立危险因素; 仅临床分期及腋淋巴结转移情况是影响患者总生存时间的独立危险因素; 而Livin均被剔除。   结论  Livin的异常高表达可能与三阴性乳腺癌的发生、发展及预后有相关性, 提示Livin的表达可能成为判断三阴性乳腺癌浸润进展及预后的指标之一。       

脂肪酸合成酶在三阴性乳腺癌中的表达及其预后价值

目的 探讨脂肪酸合成酶(fatty acid synthase,FAS)在三阴性乳腺癌(triple-negative breast cancer,TNBC)中的表达及其预后价值.方法 回顾性分析安徽省滁州市第一人民医院及江苏省肿瘤医院2006年1月至2012年12月手术病理确诊的TNBC 176例的免疫组化检测FAS的表达情况,统计学分析FAS的不同表达情况与临床病理特征及预后的相关性.结果 TNBC中FAS的阳性率为68%.FAS与肿瘤大小、组织学分级、淋巴结转移有相关性.随访显示,FAS阳性者的5年总生存率和无病生存率均低于FAS阴性者(55% vs.84%,21% vs.73%,均P<0.01).结论 TNBC中FAS阳性者预后差,FAS可能成为TNBC新的治疗靶点及预后指标.     

雄激素受体在三阴性乳腺癌中的表达及其预后价值

目的:探讨雄激素受体(androgen receptor,AR)在三阴性乳腺癌(triple-negative breast cancer,TNBC)中的表达及其预后价值。方法:回顾性分析江苏省肿瘤医院2001年1月-2006年12月手术病理确诊的TNBC 256例,免疫组化检测AR的表达情况,统计学分析AR的不同表达情况与临床病理特征的相关性,并进行随访。结果:TNBC中AR的阳性率为41%。AR与肿瘤大小、组织学分级、淋巴结转移具有统计学相关性。随访显示AR阴性者的10年总生存率和无病生存率均低于AR阳性者(68%vs 86%,19%vs 31%)。结论:TNBC中AR阳性者预后好,AR可能成为TNBC新的治疗靶点。     

GABRP在三阴性乳腺癌中的表达及其与临床病理特征和预后的关系

摘 要：［目的］ 探索三阴性乳腺癌（triple-negative breast cancer,TNBC）组织中γ-氨基丁酸A受体π亚基（gamma-aminobutyric acid type A receptor subunit pi,GABRP）的表达水平与患者临床病理资料、化疗疗效和预后的关系。［方法］ 利用 Omicsnet 数据库分析 GABRP在乳腺癌中的表达情况并分析其与临床病理特征的关系。收集2014年1月至2020年12月132例患者的临床病理资料,应用免疫组化检测132例标本中GABRP的表达情况。卡方检验分析GABRP表达与临床病理因素和化疗疗效的关系。Kaplan-Meier曲线分析GABRP表达与TNBC患者预后的关系。［结果］ 生物信息学分析发现GABRP在TNBC中高表达;GABRP表达水平与乳腺癌ER、PR、HER2、组织学分级、TP53突变、年龄、月经情况显著性相关（P＜0.05）。在132例TNBC病例中,GABRP表达与临床分期、T分期、流产史显著性相关。GABRP表达与新辅助化疗后患者的病理学疗效不相关（P＞0.05）,但与临床疗效显著性相关（P＜0.05）;GABRP高表达的患者预后更差（P＜0.05）。［结论］ GABRP在TNBC中高表达,高表达的GABRP与TNBC患者的不良预后密切相关。     

阴阳因子-1表达与乳腺癌复发转移相关性的研究

目的:探讨正常乳腺组织、乳腺癌原发病灶及乳腺癌复发转移灶中阴阳因子-1(YY1)的表达及其临床意义。方法:采用免疫组织化学SP法检测56例乳腺癌原发病灶及其对应的复发后二次手术的乳腺癌转移灶,以及20例正常乳腺组织中YY1的表达情况,并分析其与ER、PR、c-erbB-2、Ki-67和p53等多个乳腺癌相关因子及临床病理参数的关系。结果:乳腺癌复发转移灶中,YY1的阳性表达率为78.6%(44/56),显著高于乳腺癌原发病灶的51.8%(29/56)及正常乳腺组织的25.0%(5/20),差异有统计学意义,P<0.05。YY1的表达与乳腺癌组织学分级、TNM分期、腋窝淋巴结转移及复发部位相关(P<0.05),而与患者的年龄、肿瘤大小无关,P>0.05;YY1的表达与ER表达呈负相关(P<0.05),与c-erbB-2和Ki-67表达呈正相关(P<0.05),而与PR和p53表达无明显的相关性,P>0.05。结论:YY1的高表达预示着肿瘤具有较高的侵袭性和转移性,YY1有望成为乳腺癌治疗的新靶点。     

PARP1及其活性产物PAR在三阴性乳腺癌中的表达及意义

  目的  探讨聚腺苷酸二磷酸核糖转移酶（poly ADP-ribose polymerase,PARP）1及其活性产物聚腺苷酸二磷酸核糖（poly ADP-ribose,PAR）在三阴性乳腺癌（triple negative breast cancer,TNBC）及非TNBC中的表达及其意义。  方法  应用免疫组织化学染色方法检测PARP1及PAR在107例TNBC及116例非TNBC中表达差异,将患者分为TNBC组和非TNBC组。  结果  PARP1与PAR均在细胞质或（和）细胞核呈现着色表达,TNBC组细胞核PARP1表达（χ2=9.258,P=0.002）及细胞质PARP1表达（χ2=3.879,P=0.049）均高于非TNBC组;TNBC组细胞核PAR表达低于非TNBC组（χ2=6.163,P=0.013）,而细胞质PAR阳性表达明显高于非TNBC组（χ2=7.454,P=0.006）。比较细胞核/细胞质PARP1及PAR表达,均未发现PARP1与PAR表达存在明显的相关性。  结论  在TNBC组细胞核/细胞质中PARP1均高表达,并较易表现为细胞质PAR阳性表达及细胞核PAR低表达,且PARP1与PAR表达无明显相关性。      

Prognostic and predictive value of PDL1 expression in breast cancer

Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in breast cancer. Recently PD1/PDL1-inhibitors have shown promising results in different carcinomas with correlation between PDL1 tumor expression and responses. We retrospectively analyzed PDL1 mRNA expression in 45 breast cancer cell lines and 5,454 breast cancers profiled using DNA microarrays. Compared to normal breast samples, PDL1 expression was upregulated in 20% of clinical samples and 38% of basal tumors. High expression was associated with poor-prognosis features (large tumor size, high grade, ER-negative, PR-negative, ERBB2-positive status, high proliferation, basal and ERBB2-enriched subtypes). PDL1 upregulation was associated with biological signs of strong cytotoxic local immune response. PDL1 upregulation was not associated with survival in the whole population, but was associated with better metastasis-free and overall specific survivals in basal tumors, independently of clinicopathological features. Pathological complete response after neoadjuvant chemotherapy was higher in case of PDL1 upregulation (50% versus 21%). In conclusion, PDL1 upregulation, more frequent in basal breast cancers, was associated with increased T-cell cytotoxic immune response. In this aggressive subtype, upregulation was associated with better survival and response to chemotherapy. Reactivation of dormant tumor-infiltrating lymphocytes by PDL1-inhibitors could represent promising strategy in PDL1-upregulated basal breast cancer.     

三阴性乳腺癌组织Ki-67指数预后价值分析

目的 Ki-67是细胞增殖的相关抗原,Ki-67指数是区分乳腺癌Luminal A型和Luminal B型的重要生物学指标,高Ki-67指数往往预示着不良的预后.然而在三阴性乳腺癌(triple negative breast cancer,TNBC)中,Ki-67预后价值尚不明确.本研究旨在探讨TNBC中Ki-67指数的预后价值.方法 回顾性分析郑州大学附属肿瘤医院2009-01-06-2010-12-30收治的310例经病理确诊为TNBC并有完整资料和随访数据患者的临床及病理资料,分析Ki-67指数等指标对患者生存预后影响.利用SPSS 17.0软件,计数资料比较采用χ2检验.Ki-67诊断价值及截断值采用ROC曲线进行分析.生存分析采用Kaplan-Meier法,并进行Log-rank检验.多因素分析采用Cox比例风险模型.结果 中位随访时间65个月(3~81个月),310例乳腺癌患者中复发68例(21.9%),死亡49例(15.8%),其中48例死于乳腺癌(15.5%).Ki-67指数与患者月经状态(χ2=8.484,P=0.014)、肿瘤大小(χ2=17.580,P=0.007)、腋窝淋巴结状态(χ2=30.071,P<0.001)以及组织学分级(χ2=17.626,P=0.001)均相关.低(Ki-67≤20%)、中(20%50%)5年无病生存率(disease-free survival,DFS)分别为96.5%、87.3%和64.9%,差异有统计学意义,P<0.001;5年总生存率(overall survival,OS)分别为96.5%、90.2%和75.5%,差异有统计学意义,P<0.001.Ki-67评价TNBC患者DFS及OS的ROC曲线下面积分别为0.707和0.689,Ki-67评价预后最佳截断值为57.5%.单因素分析中,Ki-67指数(χ2=31.779,P<0.001)、肿瘤大小(χ2=140.260,P<0.001)、腋窝淋巴结状态(χ2=120.467,P<0.001)和组织学分级(χ2=8.765,P=0.012)是影响TNBC患者DFS的相关因素,Ki-67指数(χ2=18.218,P<0.001)、肿瘤大小(χ2=299.718,P<0.001)、腋窝淋巴结状态(χ2=68.794,P<0.001)和组织学分级(χ2=7.572,P=0.023)是影响TNBC患者OS的相关因素;多因素分析中,Ki-67指数(HR=2.074,95%CI:1.279~3.364,P=0.003)、肿瘤大小(RR=1.879,95%CI:1.152~3.062,P=0.011)和腋窝淋巴结状态(RR=2.345,95%CI:1.825~3.015,P<0.001)是影响患者DFS的独立因素,Ki-67指数(RR=1.752,95%CI:1.020~3.008,P=0.042)、肿瘤大小(RR=20.011,95%CI:1.132~3.574,P=0.017)和腋窝淋巴结状态(RR=2.021,95%CI:1.517~2.693,P<0.001)是影响患者OS的独立因素.结论 Ki-67指数与TNBC患者预后相关,高Ki-67指数患者预后不良,Ki-67指数有望成为判断TNBC患者预后的一项重要生物学指标.     

术前dNLR与三阴乳腺癌患者预后的关系

目的 探讨术前中性粒细胞／白细胞-中性粒细胞比值（dNLR）与三阴性乳腺癌临床病理特征及预后的关系。方法 回顾性分析2000年至2010年161例三阴性乳腺癌患者的临床资料,通过受试者工作特征曲线（ROC）分析dNLR的最佳截断值并将其分为高dNLR组（dNLR≥截断值） 和低dNLR组（dNLR＜截断值）,比较两组患者的临床病理特征及无病生存期（DFS） 和总生存期（OS）。用Cox比例风险模型分析影响乳腺癌患者预后的因素。结果 根据ROC曲线的结果 ,将161例患者分为高dNLR组（dNLR≥2.0,n=83）和低dNLR组（dNLR＜2.0,n=78）。乳腺癌患者术前dNLR与肿瘤体积和组织学分级有关（P＜0.05）,与年龄和淋巴结转移无关（P＞0.05）。高dNLR组与低dNLR组患者的中位DFS分别为18.1个月和24.8个月,差异有统计学意义（P＜0.001）。高dNLR组和低dNLR组患者的中位OS分别为45.9个月和78.1个月,差异有统计学意义（P＜0.001）。Cox多因素分析显示,组织学分级和术前dNLR是影响三阴性乳腺癌患者DFS的独立因素,组织学分级、肿瘤大小和术前dNLR是影响患者OS的独立因素。结论 术前dNLR 值可作为预测三阴性乳腺癌患者预后的因素。     

Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer.

BACKGROUND: AKT phosphorylation is a critical step in the activation of growth factor receptors and can mediate tumor resistance to anthracyclines. We evaluated the expression patterns and predictive value of phosphorylated AKT (pAKT) in breast cancer tissues. PATIENTS AND METHODS: pAKT expression was assessed by immunohistochemistry in 823 tumors from patients with early breast cancer enrolled in two randomized trials. The distribution of pAKT expression was correlated with HER2 and epidermal growth factor receptor (EGFR) expression. The predictive value of pAKT for the efficacy of adjuvant chemotherapy was determined by test for interaction. RESULTS: pAKT, EGFR, and HER2 were expressed in 119 of 781 (15%), 118 of 758 (16%), and 99 of 775 (13%) assessable tumors. Staining was positive for pAKT in 28 of 99 (28%) and 90 of 676 (13%) HER2+ and HER2- tumors (P < 0.001). pAKT was expressed in 15 of 94 (16%) and 75 of 563 (13%) HER2-/EGFR+ and HER2-/EGFR- tumors, respectively (P = 0.49). A positive staining for pAKT did not correlate with prognosis (P = 0.94), and did not predict the resistance to anthracyclines (test for interaction, P = 0.70). CONCLUSIONS: AKT phosphorylation is associated with HER2 expression but not EGFR expression in patients with early breast cancer. pAKT is not predictive for the efficacy of anthracycline-based adjuvant chemotherapy.     

The prognostic value of tumour-stroma ratio in triple-negative breast cancer

Background

Triple-negative cancer constitutes one of the most challenging groups of breast cancer given its aggressive clinical behaviour, poor outcome and lack of targeted therapy. Until now, profiling techniques have not been able to distinguish between patients with a good and poor outcome. Recent studies on tumour-stroma, found it to play an important role in tumour growth and progression.

Objective

To evaluate the prognostic value of the tumour-stroma ratio (TSR) in triple-negative breast cancer.

Methods

One hundred twenty four consecutive triple-negative breast cancer patients treated in our hospital were selected and evaluated. For each patient the Haematoxylin-Eosin (H&E) stained histological sections were evaluated for percentage of stroma. Patients with less than 50% stroma were classified as stroma-low and patients with ≥50% stroma were classified as stroma-high.

Results

Of 124 triple-negative breast cancer patients, 40% had a stroma-high and 60% had a stroma-low tumour. TSR was assessed by two investigators (kappa 0.74). The 5-years relapse-free period (RFP) and overall survival (OS) were 85% and 89% in the stroma-low and 45% and 65% in the stroma-high group. In a multivariate cox-regression analysis, stroma amount remained an independent prognostic variable for RFP (HR 2.39; 95% CI 1.07–5.29; p = 0.033) and OS (HR 3.00; 95% CI 1.08–8.32; 0.034).

Conclusion

TSR is a strong independent prognostic variable in triple-negative breast cancer. It is simple to determine, reproducible and can be easily incorporated into routine histological examination. This parameter can help optimize risk stratification and might lead to future targeted therapies.     

免疫治疗相关蛋白PD-1/PD-L1在三阴性乳腺癌中的表达及临床意义

目的探讨程序性死亡受体1(PDCD1,也称PD-1)及程序性死亡受体配体1(PDCD1LG1,也称PD-L1)在三阴性乳腺癌中的表达情况及其临床意义。方法收集39例三阴性乳腺癌患者和39例非三阴性乳腺癌患者的乳腺癌组织,采用免疫组织化学法检测不同乳腺癌组织中PD-1、PD-L1的表达情况,并对PD-1、PD-L1表达情况与三阴性乳腺癌患者临床特征的关系进行分析。结果三阴性乳腺癌组织中PD-1和PD-L1的阳性表达率均高于非三阴性乳腺癌组织(P﹤0.05)。不同年龄、绝经情况、组织学分级、肿瘤直径、淋巴结转移情况、肿瘤侵犯神经情况及脉管内癌栓情况三阴性乳腺癌患者的PD-1和PD-L1阳性表达率比较,差异均无统计学意义(P﹥0.05)。结论在三阴性乳腺癌中,PD-1、PD-L1具有较高的阳性表达率,检测PD-1和PD-L1的表达对早期诊断三阴性乳腺癌可能具有积极意义,同时,阻断PD-1和PD-L1信号通路可能成为三阴性乳腺癌潜在的治疗靶点。     

Prognostic value of Ki-67 according to age in patients with triple-negative breast cancer

Purpose

The prognostic value of Ki-67 in triple-negative breast cancer (TNBC) is yet unclear because the cut-off points employed differ widely and its predictive effect may vary according to age. The purpose of this study was to analyze the role of Ki-67 among patients with TNBC, and determine the optimal Ki-67 cut-off point to demonstrate its prognostic relevance associated with patient age and treatment strategy.

Methods/patients

201 consecutive patients treated for primary TNBC from 1999 to 2014 were analyzed. Clinicopathological characteristics and outcomes were compared between patients treated with neoadjuvant or adjuvant chemotherapy. We used time-dependent receiver operating characteristic (ROC) curve and time-dependent area under the ROC curve (AUC) to evaluate the discriminative ability of Ki-67 at 3 and 5 years of follow-up. A Ki-67 cut-off point that maximized sensibility and specificity was established. Interaction effect between age and Ki-67 on disease-free survival (DFS) and overall survival (OS) was evaluated by stratified analysis.

Results

According to the coordinates of the ROC curves, the best cut-off point for Ki-67 was 60% (high/low). In the whole group, there was not a statistically significant association between Ki-67 and OS and DFS, using a cut-off point of 60%. In multivariate analysis (COX proportional hazards regression), for DFS high Ki-67 (>?60%) was a poor prognostic factor in patients?>?40 years old and a better prognostic factor among the patients?<?40 years old.

Conclusion

Prognostic value of Ki-67 in TNBC, using a cut-off point of 60%, may vary depending on age.

     

Prognostic and predictive value of thymidine phosphorylase activity in early-stage breast cancer patients

The antitumor effects of 5-fluorouracil (5-FU) and its derivatives depend upon the activity of nucleoside metabolic enzymes in tumor tissues. Thymidine phosphorylase (TP) converts 5'-deoxy-5-fluorouridine (5'-DFUR), an intermediate metabolite of capecitabine, to 5-FU. The relationship between TP expression in tumor tissues and patient survival was retrospectively examined in early-stage breast cancer patients treated with either oral 5'-DFUR administered for 6 months or surgery alone in a prospective randomized controlled trial. Thymidine phosphorylase expression in tumor cells and tumor-associated stromal (TAS) cells was examined by immunohistochemistry in 650 tissue samples from patients in this trial (n = 1217). Eight-year follow-up data showed that high TP expression in tumor cells was a significant prognostic indicator of a favorable outcome only for the patients in the 5'-DFUR group. Thus, TP expression was shown to be a predictive factor of 5'-DFUR efficacy. Conversely, a low TP expression in TAS cells was also a potent favorable prognostic indicator. These results on TP status in 2 tumor cell types could provide novel information for predicting prognosis for a patient subgroup, which would receive a probable therapeutic effect from 5'-DFUR, and presumably, from adjuvant therapy of capecitabine in early-stage breast cancer. Determination of TP status might also identify a patient subgroup whose prognosis is quite favorable even without adjuvant therapy. Further investigations on prognostic and predictive implications of TP activity in a clinical setting are warranted.