SUVmax、Ki-67、p53、EGFR对三阴性乳腺癌新辅助化疗疗效的预测价值

目的 探讨18F-FDG PET/CT化疗前SUVmax、Ki-67、p53、EGFR对三阴性乳腺癌（TNBC）及非三阴性乳腺癌（非TNBC）对新辅助化疗完全病理缓解（pathologic complete response, pCR）率的预测价值。方法 初治TNBC患者27例,非TNBC患者184例,在新辅助化疗前行18F-FDG PET/CT显像并测量其SUVmax,取化疗前乳腺肿瘤组织进行Ki-67、p53、EGFR免疫组织化学分析并计算化疗后完全pCR率。结果 TNBC新辅助化疗前的SUVmax明显高于非TNBC的SUVmax（P=0.045）,TNBC新辅助化疗后pCR率明显高于非TNBC（P＜0.001）。在TNBC以及非TNBC中,达到pCR组的化疗前SUVmax与未达到pCR组之间差异无统计学意义（P＞0.05）。Ki-67、p53、EGFR阳性表达组的pCR率与阴性表达组之间差异无统计学意义（P＞0.05）。结论 TNBC对新辅助化疗的敏感度高于非TNBC,且TNBC化疗前SUVmax高于非TNBC,提示TNBC具有较高的能量代谢。化疗前SUVmax以及Ki-67、p53、EGFR不能预测TNBC及非TNBC新辅助化疗的pCR。     

Ki-67表达与多西他赛联合顺铂治疗三阴性乳腺癌疗效的关系

目的：探讨三阴性乳腺癌（ TNBC）组织Ki-67表达与多西他赛联合顺铂化疗疗效之间的关系。方法选取术后胸壁局部复发和（或）区域淋巴结转移的女性TNBC患者50例,复发或转移病灶行穿刺活检术,应用免疫组化方法检测Ki-67的表达,分为区域淋巴结转移组、无区域淋巴结转移组,Ki-67阳性表达组及阴性表达组。应用多西他赛联合顺铂方案化疗,3周期后进行疗效评价。结果区域淋巴结转移组及无区域淋巴结转移组Ki-67阳性表达差异有统计学意义（χ2=4.402,P=0.036）。3周期化疗后Ki-67阳性表达组有效率85.71%（30/35）,Ki-67阴性表达组有效率60.00%（9/15）,差异有统计学意义（χ2=4.406,P=0.044）。结论多西他赛联合顺铂治疗术后出现胸壁局部复发和（或）区域淋巴结转移的TNBC疗效较好, Ki-67阳性表达的TNBC患者对该方案化疗更敏感。     

Ki-67对三阴性乳腺癌新辅助化疗敏感性预测作用的Meta分析

目的:评价新辅助化疗中Ki-67的表达情况对三阴性乳腺癌(TNBC)获得病理完全缓解(pCR)的预测作用。方法:通过互联网检索相关文献,应用Review Manager软件对数据进行处理,系统评价Ki-67表达情况与TNBC在新辅助化疗中获得pCR的关系。结果:Ki-67基因高表达的TNBC患者pCR率明显高于Ki-67基因低表达的TNBC患者,总体合并优势比(OR)为7.35,95%CI:2.39～22.60,文献之间无明显异质性,无明显发表偏倚。结论:Ki-67可作为新辅助化疗中预测TNBC化疗敏感性的标志。     

Ki-67表达与Ⅱ/Ⅲ期乳腺癌新辅助化疗疗效及预后的关系

目的:探讨乳腺癌组织中Ki-67 抗原（简称 Ki-67）表达与新辅助化疗(neoadjuvant chemotherapy,NAC)疗效的关系。寻找新辅助化疗有效的预测因子。方法:选取我院2012年6月至2017年6月收治的112例接受NAC治疗的Ⅱ/Ⅲ期乳腺癌患者作为研究对象。使用免疫组化方法检测NAC治疗前乳腺癌患者的Ki-67表达情况，化疗2~4周期后评估临床疗效。分析乳腺癌中Ki-67的表达与临床病理学特征的关系以及Ki-67的表达与NAC疗效的关系。结果:原发性乳腺癌组织中Ki-67的高表达率为65.18%，Ki-67的高表达与病理组织学分级（P=0.017）有关。Ki-67高表达的患者新辅助化疗后获得临床完全缓解（cCR）+临床部分缓解（cPR）的比率（89.0%）明显高于Ki-67低表达的患者新辅助化疗后获得cCR+cPR的比率（61.5%）（P=0.001）。中位随访时间 37个月，Ki-67高表达患者的无病生存时间（DFS）低于Ki-67低表达的患者（P=0.023），Ki-67高表达患者的总生存时间（OS）低于Ki-67低表达的患者（P=0.040）。结论:Ki-67的高表达与乳腺癌恶性程度密切相关，并可作为预测乳腺癌新辅助化疗敏感度及预后的独立指标。     

Ki-67与乳腺癌临床病理特征及新辅助化疗疗效的相关性

目的：分析Ki-67与乳腺癌临床病理特征对新辅助化疗（neoadjuvant chemotherapy,NCT）疗效和预后的影响,探讨NCT疗效的预测因素。方法用免疫组化法检测320例局部晚期乳腺癌患者癌组织中ER、PR、HER-2及Ki-67表达状况。进行NCT 4～6个周期后手术。分析临床病理特征与病理完全缓解率（patho-logic complete response,pCR）之间的关系。临床病理参数与疗效分析用χ2检验,影响预后因素用Cox多因素回归分析。结果 Ki-67表达与ER（r=－0.174,P=0.002）和PR（r=－0.132,P=0.019）呈负相关,与HER2（r=0.140, P=0.012）和乳腺肿瘤大小（r=0.132,P=0.019）呈正相关;ER阴性组pCR率显著高于ER阳性组（26.9%vs 7.4%,χ2=22.761,P=0.000）;PR阴性组pCR率显著高于阳性组（22.7%vs 10.9%,χ2=7.950,P=0.005）;Ki-67高表达组pCR率18.0%（41/228）优于Ki-67低表达组8.6%（8/92）（χ2=4.552,P=0.033）;化疗后Ki-67表达下降组pCR率19.8%（48/243）优于未下降组1.3%（1/77）（χ2=15.356,P=0.000）;各分子亚型间化疗疗效差异显著,Luminal A型pCR率为1.4%（1/71）,Luminal B型pCR率为15.3%（25/163）,HER2过表达型pCR率为31.3%（14/45）,三阴性型pCR率为22.0%（9/41）（χ2=20.639,P=0.000）;用Kaplan-Meier法进行生存分析,Ki-67低表达组无病生存时间（DFS）和总生存时间（OS）均优于Ki-67高表达组,两者均为P=0.034。结论 Ki-67高表达患者对化疗更敏感,但预后较差。化疗前Ki-67的表达和化疗后Ki-67变化是影响DFS独立的预后因素。ER、PR、Ki-67指数及分子分型可以作为NCT疗效的预测指标,Ki-67指数与ER、PR、HER2之间存在相关性。     

三阴性乳腺癌组织p53和Ki-67及E-cadherin的表达及其意义

目的:探讨p53、Ki-67和E-cad-herin在三阴性乳腺癌(TNBC)组织中的表达及在预后中的意义。方法:42例TNBC患者为TNBC组,随机抽取同期非TNBC42例为对照组,统计2组p53、Ki-67和E-cadherin的表达。结果:p53在TNBC组的表达率为76.19%(32/42),对照组为54.76%(23/42),差异有统计学意义,P=0.039。Ki-67在TNBC组的表达率为85.71%(36/42),对照组为61.90%(26/42),差异有统计学意义,P=0.013。E-cadherin在TNBC组的表达率为45.24%(19/42),对照组为66.67%(28/42),差异有统计学意义,P=0.048。结论:p53、Ki-67的高表达和E-cadherin的低表达与TNBC预后差密切相关。     

Ki-67抗原与子宫颈鳞癌新辅助化疗和放疗的敏感性研究

目的探讨Ki-67抗原与子宫颈鳞癌新辅助化疗（NACT）和放射治疗（RT）的敏感相关性。方法在新辅助化疗前后用免疫组化检测32例宫颈鳞癌组织Ki-67的表达。结果化疗前患者Ki-67的表达水平在不同年龄段组（〈45岁和≥45岁）、不同临床期别组（Ⅰb～Ⅱa和Ⅱb～Ⅲb）和不同病理分级组（高中分化和低分化）之间相互比较差异有统计学意义（P=0.008、0.009、0.000）。化疗后患者Ki-67表达水平与化疗前比较明显下降,差异有统计学意义（P=0.000）。化疗前Ki-67表达程度不同,化疗和化放疗的疗效明显不同,化疗疗效高表达组与低表达组比较差异有统计学意义（P=0.033）;化放疗疗效高表达组与低表达组比较差异无统计学意义（P=0.375）;高表达组、低表达组对化疗和化放疗的疗效比较差异均有统计学意义（P=0.001、0.000）。结论子宫颈鳞癌治疗前Ki-67表达强度与化疗敏感性呈正相关;虽然存在Ki-67阳性表达强度愈强、NACT＋RT的完全缓解率愈高的趋势,但未显示明显的放射敏感相关性;治疗前检测Ki-67表达可以为预测化疗和放疗敏感性提供客观依据,但Ki-67能否确定为预测子宫颈鳞癌新辅助化疗和放疗敏感性的可靠指标还需增加样本作进一步研究。     

EpCAM和Ki-67在三阴性乳腺癌原发灶及淋巴结转移灶中的表达及临床意义

目的 探讨上皮细胞黏附分子（EpCAM）和Ki-67在三阴性乳腺癌（TNBC）原发灶和淋巴结转移灶中的表达及临床意义。方法 用免疫组化染色检测81例TNBC原发灶、43例淋巴结转移灶及20例癌旁正常乳腺组织中EpCAM和Ki-67的表达情况。结果 EpCAM和Ki-67在TNBC组织中的过表达率分别为74.1％和61.7％,均高于癌旁正常乳腺组织,差异有统计学意义（P＜0.05）; EpCAM蛋白表达与TNBC的组织学分级、淋巴结转移有关（P＜0.05）;Ki-67蛋白表达与组织学分级、淋巴结转移及pTNM分期有关（P＜0.05）;TNBC组织中EpCAM和Ki-67蛋白表达呈正相关（r=0.462,P＜0.001）。在43例伴有淋巴结转移的TNBC患者中,淋巴结转移灶和原发灶中EpCAM和Ki-67蛋白均呈高表达,Ki-67在淋巴结转移灶中的表达率高于原发灶（P＜0.05）。结论 EpCAM和Ki-67在TNBC原发灶及淋巴结转移灶中均高表达;EpCAM和Ki-67过表达可能与TNBC的发生、发展密切相关。     

Ki - 67、AR 及 FRA 在三阴性乳腺癌中的表达及意义

目的：观察Ki-67、雄激素受体（androgenreceptor,AR）和a-叶酸受体（folatereceptoralpha,FRA）在三阴性乳腺癌（triplenegativebreastcancer,TNBC）组织中的表达,探讨Ki-67、AR、FRA与TNBC预后的关系。方法：应用免疫组织化学法检测Ki-67、AR及FRA在80例TNBC组织中的表达,分析其与TNBC患者临床病理特征的相关性及与预后的关系。结果：TNBC组织中Kj-67、AR、FRA阳性率分别为81．25％、25．00％、71．25％。Ki-67、FRA阳性表达率与TNBC患者高淋巴结转移、低组织学分级和5年生存时间有关,并有统计学意义（P〈0．05）。AR阳性表达率与TNBC高组织学分级和5年生存时间有关且有统计学意义（P〈0．05）。Ki-67、FRA表达高者,生存时间短,且与5年生存时间呈负相关（r=-0．371,r=-0．498）;AR表达高者,生存时间长,与5年生存时间呈正相关（r=0．465）。Ki-67与FRA表达呈正相关（r=0．332）,与AR表达呈负相关（r=-0．462）。结论：TNBC组织中Ki-67、FRA阳性者预后差,AR阳性者预后良好,联合检测这三个抗体的表达,可能为评价TNBC预后提供新指标,为TNBC的治疗提供新靶点。     

乳腺癌穿刺活检对HR和HER-2及Ki-67评价可靠性以及化疗对其影响研究

目的：研究乳腺癌空芯针穿刺活检（coreneedle biopsy,CNB）对激素受体（hormone receptor,HR）、HER-2及Ki-67表达状况评价的可靠性,探讨新辅助化疗（neoadjuvantchemotherapy,NAC）对乳腺癌分子生物学信息表达的影响,分析上述生物学指标对NAC疗效的预测价值。方法：选择2012-03-01-2013-01～31山东省肿瘤医院外科收治的乳腺癌患者177例,其中行NAc者95例作为NAC组,未行NAC者82例作为对照组。免疫组织化学SP法检测两组患者CNB和治疗性手术切除标本中ER、PR、HER-2及Kb67的表达状况,依据Miller-Payne分级系统评价化疗后病理反应,依据实体瘤反应评价标准（response evaluation criteria in solid tumors,RECIST）进行新辅助化疗的疗效评价。结果：对照组患者cNB和手术切除标本ER表达一致率为97．6％（80／82）,PR为95．1％（78／82）,HER-2为97．6％（80／82）,Ki-67为92．7％（76／82）,Spearman等级相关系数均〉0．8,P均〈0．05。NAC组和对照组CNB和手术切除标本比较,ER表达状况改变率分别为12．4％（10／79）和3．9％（2／82）,差异有统计学意义,P=0．014;PR表达状况改变率分别为24．0％（19／79）和2．4％（4／82）,差异有统计学意义,P=0．001;HER-2表达状况改变率分别为5．1％（4／79）和2．4％（2／82）,差异无统计学意义,P=0．379;Ki=67表达状况改变率分别为38．0％（30／79）和7．3％（6／82）,差异有统计学意义,Pd0．001。NAC前后ER阳性率分别为64。6％和53．2％,差异无统计学意义,P=0．146;PR阳性率分别为63．3％和45．6o／,差异有统计学意义,P=0．025;Ki-67高表达率分别为45．6％和15．2％,差异有统计学意义,P=0．017。化疗反应分级与ER、PR、HER-2表达变化无相关性,P均〉0．05;与Ki-67表达变化明显相关,P=0．008。ER和PR表达状况与NAC疗效无相关性,P均〉0．05;HER-2阳性的乳腺癌患者NAC有效率为81．8％,阴性者有效率为50．7％,差异有统计学意义,P=0．010;Ki-67高表达乳腺癌患者NAC有效率为70．2％,低表达者有效率为45．5％,差异有统计学意义,P=0．029。结论：cNB与手术切除标本在判断HR、HER-2和Ki-67表达状况上有很好的一致性;NAC能改变乳腺癌患者HR和Ki-67的表达状况,NAc使PR的阳性率降低,Ki-67的表达下降,ER阳性率有降低趋势,NAc对HER-2的表达无显著影响;HER-2阳性和Ki-67高表达的患者对化疗更敏感。     

Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: Correlation between Androgen Receptor Expression and Pathological Response

Background: There is growing evidence that the response to chemotherapy may be affected by Androgen Receptor (AR) expression suggesting that triple-negative breast cancers (TNBC) AR+ and quadruple negative breast cancer (QNBC) subtypes may have different diseases behavior. Methodology: We retrospectively estimated the predictive value of the AR expression in stage II and stage III TNBC patients treated with neoadjuvant chemotherapy (NAC) and correlated with the rate of pathological response (pCR). Results: Of 89 TNBC patients, 29 patients (32.6%) were TNBC AR+ and 60 patients (67.4) were QNBC. Most of the patients were less than 60 years old. Of note, approximately 62% in the QNBC group were less than 40 years old compared with 39 % in the TNBC AR+ group. The Ki-67 expression was higher in the QNBC in comparison with TNBC AR+ being 86.7% and 65.5%, respectively. QNBC subgroup showed higher rates of pCR compared with TNBC; 60% and 24%, respectively. Higher Ki-67 expression, higher grade, and lymph node involvement were statistically significantly correlated with the rate of pCR in the QNBC group (p=0.02, p=0.04, and p=0.03, respectively). In contrast, no significant association was observed between pCR and clinical-pathological features in the TNBC AR+ group. Conclusion: Our results suggested that the AR expression in TNBC may be applied as a predictive marker for NAC. TNBC AR+ had a lower rate of pCR compared with QNBC, suggesting that this subtype may have a partial chemoresistance.     

Predictive Significance of p53, Ki-67, and Bcl-2 Expression for Pathologic Complete Response after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer

Purpose

Patients with triple-negative breast cancer (TNBC) with pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) have superior survival outcomes compared to those with residual disease after NAC. This study investigated the value of three biomarkers, p53, Ki-67, and Bcl-2 for predicting pCR in NAC-treated patients with TNBC.

Methods

Between 2003 and 2012, 198 patients with pathologically confirmed primary TNBC were treated with two different taxane-based chemotherapeutic regimens prior to surgery. Before NAC, expression of p53 (cutoff 25%), Ki-67 (cutoff 10%), and Bcl-2 (cutoff 10%) was assessed immunohistochemically in core biopsy specimens. The incidence of pCR was correlated with the expression of these biomarkers.

Results

Overall, pCR occurred in 37 of the 198 patients (18.7%). A significant association was observed between the pCR rate and overexpression of the p53 and Ki-67 biomarkers. Multivariate analysis showed that only p53 expression was independently associated with pCR to NAC (odds ratio, 3.961; p=0.003). The sensitivity, specificity, positive predictive value, and negative predictive value of p53 expression for predicting pCR were 77.8%, 50.3%, 26.2%, and 90.9%, respectively. The pCR rate was the lowest (5.2%) in patients with low expression of both p53 and Ki-67, and it was the highest (25.8%) when both biomarkers showed high expression.

Conclusion

Expression of p53 was significantly associated with pCR after NAC in patients with TNBC, suggesting that this biomarker might be particularly valuable in identifying TNBC patients prone to have residual disease after NAC.     

Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis

Introduction

Triple negative breast cancer (TNBC) has a poorer survival, despite a higher response rate to neoadjuvant chemotherapy. The purpose of this study was to identify the predictive or prognostic value of Ki-67 among patients with TNBC treated with neoadjuvant chemotherapy, and the role of Ki-67 in further classification of TNBC.

Methods

A total of 105 TNBC patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were included in the present study. Pathologic complete response (pCR) rate, relapse-free survival (RFS), and overall survival (OS) were compared according to the level of Ki-67.

Results

pCR was observed in 13.3% of patients. TNBC with high Ki-67 expression (≥10%) showed a higher pCR rate to neoadjuvant chemotherapy than TNBC with low Ki-67 expression. None of the low Ki-67 group achieved pCR (18.2% in the high Ki-67 group vs. 0.0% in the low Ki-67 group, P = 0.019). However, a high Ki-67 expression was significantly associated with poor RFS and OS in TNBC, despite a higher pCR rate (P = 0.005, P = 0.019, respectively). In multivariate analysis, high Ki-67 was an independent prognostic factor for RFS in TNBC (hazard ratio = 7.82, P = 0.002). The high Ki-67 group showed a similar pattern of recurrence with overall TNBC, whereas the low Ki-67 group demonstrated a relatively constant hazard rate for relapse.

Conclusions

TNBC with high Ki-67 was associated with a more aggressive clinical feature despite a higher pCR rate. High proliferation index Ki-67 can be used for further classification of TNBC into two subtypes with different responses and prognosis.     

A prognostic model based on combining estrogen receptor expression and Ki-67 value after neoadjuvant chemotherapy predicts clinical outcome in locally advanced breast cancer: Extension and analysis of a previously reported cohort of patients

Background

Ki-67 expression has gained attention as a breast cancer prognostic factor, however its significance in the remaining malignant cells after neoadjuvant chemotherapy (NAC) has been rarely examined. This investigation, extension and analysis of a previously reported cohort of patients, evaluates the significance of Ki-67 and estrogen receptor (ER) expression after NAC in LABC (locally advanced breast cancer).

Patients and methods

clinical stage, tumor size, clinical and pathological lymph node involvement, Ki-67, ER, progesterone receptor (PgR), HER2 expression, grading and clinical response were evaluated before and after NAC in 110 patients with LABC. Ki-67 expression was assessed both in pre and post-therapy histological samples, using >15% positive cells as cut-off value to distinguish high from low Ki-67 expressing tumors.

Results

six patients (5.45%) attained pCR after NAC. A significant relationship between elevated post-CT Ki-67 and ER expression was showed at Cox multivariate analysis of disease free survival (DFS).On univariate analysis high post-chemotherapy Ki-67 and ER status were associated with worse survival; at multivariate model included these results were confirmed.Based on these two parameters, a prognostic model identified two different groups: low risk (low postchemotherapy Ki-67 and ER positive, or either high post-chemotherapy Ki-67 or ER negative), and high risk (high post-chemotherapy Ki-67 and ER negative).The low risk group showed a good prognosis (median OS still not reached), while the high risk group had a worse OS (median 41 months).

Conclusions

Ki-67 value after NAC and ER status could predict a worse prognosis among LABC patients treated with NAC.     

影响青年乳腺癌患者新辅助化疗后病理完全缓解和预后的病理因素分析

目的:探讨影响青年乳腺癌患者新辅助化疗（neoadjuvant chemotherapy,NAC）后病理完全缓解（pathological complete response,pCR）和预后的临床病理因素。方法:回顾性分析2010年01月至2018年12月我院甲乳外科收治年龄≤35岁行NAC的女性乳腺癌患者的临床病理资料。NAC后依据Miller-Payne评分系统,将患者分为pCR组和非pCR组。探讨临床病理因素对青年乳腺癌患者pCR、复发转移和死亡的影响,同时分析pCR与无病生存期（disease free survival,DFS）与总生存期（overall survival,OS）之间的相关性。结果:168例患者中pCR 37例,pCR率为22.0%。体质量指数(body mass index,BMI)、术前淋巴结状态、雌激素受体（estrogen receptor,ER）、孕激素受体（progesterone receptor,PR）、人类表皮生长因子受体2（human epidermal growth factor receptor-2,HER-2）、Ki-67、p53及分子分型与青年乳腺癌患者NAC后的pCR率关系密切（P＜0.05）。肿瘤大小、术前淋巴结状态、ER、PR、HER-2、p53及分子分型影响患者的复发转移和死亡（P＜0.05）,同时肿瘤大小、术前淋巴结状态、组织学分级、ER、PR、HER-2、Ki-67及分子分型均是DFS和OS的独立影响因素（P＜0.05）。66例复发转移患者中pCR患者7例,占pCR患者的18.9%（7/37）,pCR组和非pCR组DFS比较差异具有统计学意义（P＜0.05）。38例死亡患者中pCR患者3例,占pCR患者的8.1%（3/37）,pCR组和非pCR组OS比较差异具有统计学意义（P＜0.05）。结论:影响青年乳腺癌患者pCR和预后的临床病理因素较多,获得pCR的患者具有更好的远期预后。     

Ki-67、CDK4表达与中晚期乳腺癌新辅助化疗效果的相关性分析北大核心

目的:分析Ki-67核抗原(Ki-67)、CDK4表达与中晚期乳腺癌新辅助化疗(NACT)效果的相关性。方法:回顾性选取2016年4月至2018年6月我院的中晚期乳腺癌患者70例,均于新辅助化疗后实施手术,依据化疗效果分为有效组、无效组,采用免疫组化法检测两组化疗前Ki-67、CDK4表达水平,比较不同Ki-67、CDK4表达水平患者病理完全缓解率(pCR)、2年复发转移情况。结果:有效组Ki-67高表达率、CDK4阳性率高于无效组(P<0.05);Ki-67高表达患者pCR率高于Ki-67低表达者,CDK4高表达者pCR率高于CDK4低表达者(P<0.05);Kaplan-Meier曲线显示,Ki-67低表达的乳腺癌患者2年复发转移率低于Ki-67高表达者(P<0.05),CDK4高表达的乳腺癌患者2年复发转移率与CDK4低表达者无明显差异(P>0.05);Spearman相关分析显示,乳腺癌患者Ki-67、CDK4表达变化与化疗效果呈正相关(r=0.569、0.481,P<0.05)。结论:Ki-67、CDK4高表达的乳腺癌患者经NACT后获得pCR率更高,化疗疗效更优,但Ki-67高表达者预后较差,CDK4表达情况与预后相关性不大。     

Predictive factors for the effectiveness of neoadjuvant chemotherapy and prognosis in triple-negative breast cancer patients

Purpose

Triple-negative breast cancers (TNBCs) do not derive benefit from molecular-targeted treatments such as endocrine therapy or anti-HER2 therapy because they lack those molecular targets. On the other hand, TNBCs have been shown to respond to neoadjuvant chemotherapy (NAC). In this study, we analyzed TNBC patients who were treated with NAC at Osaka National Hospital over a recent 5-year period to clarify the predictive factors for NAC and prognostic factors.

Patients and methods

Thirty-three TNBC patients underwent sequential NAC with anthracycline (FEC100: 5FU 500 mg/m², epirubicin 100 mg/m², and cyclophosphamide 500 mg/m²/q3w, 4 courses) and taxanes (paclitaxel 80 mg/m²/qw, 12 courses or docetaxel 75 mg/m²/q3w, 4 courses) from May 2003 to July 2008. Pre-therapeutical and surgical specimens were studied for expressions of ER, PgR, HER-2, EGFR, cytokeratin 5/6, Ki-67, p53 and androgen receptor by immunohistochemistry (IHC). We analyzed clinicopathological factors and molecular markers in regard to the response to NAC and prognosis.

Results

Pathological complete response (pCR) was achieved in 12 TNBC patients (36%). The pCR rate in the basal-like phenotype was significantly lower than in the non-basal-like phenotype (23 vs. 64%, respectively: P = 0.02). High pre-operative expressions of Ki-67 (≥50%) and HER-2 (2+) were considered as predictive factors for a better response from NAC. Pre-operative Ki-67 expression showed a significant correlation with disease-free survival (DFS) and a lower expression of Ki-67 (<50%) after NAC was favorable for DFS among non-pCR patients.

Conclusions

A non-basal-like phenotype and higher expressions of Ki-67 and HER-2 (2+) were favorable factors for NAC. However, a higher expression of Ki-67 on the surgical specimen after NAC was also a poor prognostic factor.     

外周血淋巴细胞和单核细胞比值对三阴性乳腺癌新辅助化疗疗效的预测价值

目的:探讨外周血淋巴细胞和单核细胞比值(lymphocyte-to-monocyte ratio,LMR)对三阴性乳腺癌(triple negative breast cancer,TNBC)患者新辅助化疗(neoadjuvant chemotherapy,NAC)疗效的预测价值.方法:收集2017年01月至2019年...     

Survival outcome and reduction rate of Ki-67 between pre- and post-neoadjuvant chemotherapy in breast cancer patients with non-pCR

The research question of this investigation is whether the reduction rate of Ki-67 after neoadjuvant chemotherapy (NAC) could indicate a survival in patients with non-pCR. A total of 455 patients had received NAC, and subsequent surgery was analyzed retrospectively. Patients with non-pCR were divided into three subgroups according to Ki-67 change: High-reduction (the absolute value of Ki-67 was reduced by >80 % compared with that prior to NAC), Low-reduction (the absolute value of Ki-67 was reduced by 0–80 % compared with that prior to NAC), and Increase group (the absolute value of Ki-67 was increased compared with that prior to NAC). The relapse-free survival (RFS) rates were compared among subgroups. pCR was achieved in 93 patients (20.4 %). In patients with non-pCR, the median reduction rate of Ki-67 was 60 %. A total of 15 % of patients were in the High-reduction, 63 % in the Low-reduction, and 22 % in the Increase group. The median follow-up period was 64.5 months. The 5-year RFS rates among the three groups were significantly different (p < 0.0001), and the differences were also observed in the HER2 (p = 0.033), triple-negative (p = 0.034), and luminal-like subtypes (p = 0.001). Patients in the High-reduction group showed comparable RFS to that of patients with pCR (p = 0.363). In patients with non-pCR, the reduction rate of Ki-67 after NAC significantly predicted RFS regardless of cancer subtypes. Therefore, patients who are non-pCR but who achieve a high reduction of Ki-67 can be expected to have a favorable prognosis similar to that of patients with pCR.