乳腺癌新辅助化疗的疗效预测因子

乳腺癌的新辅助化疗已经成为乳腺癌治疗策略的一部分,并逐渐应用于早期乳腺癌[1],通过减少肿瘤体积,部分可达到保乳目的 ,而且理论上可以减少微小转移灶的播散,并观察药物的疗效。新辅     

乳腺癌新辅助化疗的临床疗效观察

目的 观察和探讨泰素单药或联合蒽环类药物的Weekly方案在乳腺癌新辅助化疗应用中的临床疗效。 方法 对42例乳腺癌患者,确诊后立即行以泰素（TXL）单药或联合表阿霉素（EPI）的Weekly方案新辅助化疗，术前术后各3周，化疗1～4个疗程,每疗程间隔3周。术前化疗无效者术后改用其他化疗方案。结果 术前无达到临床完全缓解（CR）者。本组术前有效35例，其中PR 6例、MR 29例，有效率83.3%。10例行保乳手术，32例行改良根治术。化疗过程中，没有出现严重的化疗毒性。结论 Weekly方案治疗乳腺癌副作用小，疗效肯定，术前应用可为手术提供更多的选择机会，并为筛选敏感的化疗药物提供参考，是一种安全有效的辅助治疗方法，值得临床推广和应用。     

乳腺癌新辅助化疗疗效评价及预测的研究进展

新辅助化疗作为乳腺癌综合治疗的一项重要治疗手段,已经在临床治疗中广为应用。目前临床上对新辅助化疗疗效评价主要依靠临床触诊、影像学检测、病理学检测。随着人们对新辅助化疗的疗效评价及预测作用认识的提高,从生物学因子水平了解肿瘤的变化已成为新辅助化疗疗效评价的主要研究方向。联合多个生物学因子的多基因表达谱分析,有望能够预测新辅助化疗的疗效,为个体化治疗提供依据。     

40例乳腺癌新辅助化疗的疗效观察

目的评价含紫杉类或葸环类药物在乳腺癌术前化疗中的疗效及副作用。方法2005年7月～2007年11月在我院治疗的40例Ⅰ～Ⅲ期原发乳腺癌患者,采用含紫杉类（TP或TE／TEC方案）或葸环类（EC／FEC方案）联合方案,术前化疗2～4个周期,33例患者接受手术,术后完成规定化疗,应用B超结合触诊判断临床疗效,观察近期疗效及毒副作用,应用x^2检验及单因素分析判定相关因素与疗效的关系。结果化疗前后中位肿瘤最大径分别为3．5厘米和2．0厘米（P=0．01）,临床有效率82．5％（33／40）,其中cCR7．5％（3／40）、cPR75％（30／40）、cSD15％（6／40）、cPD2．5％（1／40）。手术治疗33例,术后pCR9．1％（3／33）,tpCR6．1％（2／33）。这些病例中,不同肿瘤大小、受体状况、CerbB-2表达、不同分化程度以及化疗方案之间的肿瘤缓解率并无统计学差异。化疗毒副作用主要为脱发、骨髓抑制、消化道反应、口腔溃疡及外周神经毒性,心脏毒性主要表现为心律增快、心电图改变,肝功损害少见。结论紫杉类及蒽环类药物联合方案用于浸润性乳腺癌的术前化疗,可有效控制肿瘤,毒副作用可耐受。     

乳腺癌组织学类型及分级对预测新辅助化疗疗效的价值

目的:分析乳腺癌不同组织学类型及分级在新辅助化疗疗效预测中的价值。方法:细针穿刺活检确诊的53例乳腺癌病例,给予蒽环类新辅助化疗2周期,化疗前明确组织学类型、分级等临床病理特征,化疗后行乳腺改良根治术并行术后病理检测,评估化疗疗效,分析各临床病理特征与化疗疗效的关系。结果:53例乳腺癌患者新辅助化疗后,病理缓解(包括部分及完全缓解)41例(77.4%),其中病理完全缓解3例(5.7%)。新辅助化疗疗效与组织学类型及分级密切相关(P<0.01),与年龄、是否绝经及原发肿瘤期别均无关(P>0.05)。结论:新辅助化疗疗效仅与组织学类型及分级相关,浸润性导管癌化疗的疗效较非浸润性导管癌疗效佳。组织学分级高者优于分级低者,组织学亚型及级别可作为新辅助化疗敏感病例选择的预测因子。     

乳腺癌生物标记物表达水平对新辅助化疗疗效的预测价值

目的探讨乳腺癌生物标记物雌激素受体(ER)、人类表皮生长因子受体-2(HER-2)、P53和Ki67的表达与新辅助化疗疗效之间的关系。方法对2007年10月至2009年9月在北京大学第一医院乳腺疾病中心接受4～6个周期紫杉类联合蒽环类方案新辅助化疗的165例乳腺癌患者资料进行回顾性分析。用免疫组织化学方法检测新辅助化疗前肿瘤病灶ER、HER-2、P53和Ki67的表达情况,用术后病理评价新辅助化疗疗效,病理学反应级别为G4、G5则认为化疗有效。用四格表资料的χ2检验法分析上述指标与新辅助化疗疗效之间的关系。结果 165例患者中56.4%(93/165)新辅助化疗有效。ER阳性者有效率为43.5%(20/46),ER阴性者有效为61.3%(73/119),两组之间差异有统计学意义(χ2=4.31,P=0.04);HER-2过表达者有效率为72.0%(36/50),低表达者为49.6%(57/115),二者差异有统计学意义(χ2=7.13,P=0.01);P53阳性者有效率为66.7%(30/45),阴性者为53.4%(47/88),两组间差异无统计学意义(χ2=2.15,P=0.14);Ki67过表达者化疗有效率为62.4%(68/109),低表达者为44.0%(22/50),两组间差异有统计学意义(χ2=4.72,P=0.03)。结论 ER阴性、HER-2及Ki67过表达者对紫杉联合蒽环方案的新辅助化疗更敏感,ER、HER-2及Ki67表达情况对新辅助化疗疗效有预测作用。     

CEUS参数定量分析在乳腺癌新辅助化疗疗效中的预测价值

摘 要：［目的］ 探究CEUS指标对乳腺癌患者新辅助化疗(neoadjuvant chemotherapy,NAC)疗效的预测价值。［方法］ 选择2018年10月至2019年5月在陆军军医大学第二附属医院行NAC治疗的乳腺癌患者51例,均使用紫杉醇联合顺铂治疗,于NAC治疗结束后行CEUS,并于1周内行手术切除,根据术后病理切片是否达到病理完全缓解（pCR）将患者分为反应组与对照组,对比两组CEUS结果,应用ROC曲线评估CEUS指标对疗效的预测价值。［结果］ 本研究共有16例（31.37%）达pCR;反应组峰值强度、区域血流量及肿瘤直径显著性小于对照组（P均<0.05）,平均通过时间显著性大于对照组（t=2.351,P=0.023）;峰值强度、区域血流量、平均通过时间、肿瘤直径在最佳截点预测NAC疗效的AUC分别为0.888、0.821、0.923和0.941,各指标间无显著性差异（P＞0.05）;肿瘤直径的预测特异性显著性高于区域血流量（97.14% vs 77.14%;χ2=6.248,P=0.012）。［结论］ CEUS定量分析对于乳腺癌患者NAC疗效具有较好预测价值,值得进一步研究探讨。     

IGF-ⅠR对乳腺癌新辅助化疗疗效的预测价值

[目的]探索IGF-Ⅰ R对乳腺癌新辅助化疗(NAC)疗效的预测价值.[方法]纳入40例接受NAC的原发性乳腺癌患者,测定NAC前肿瘤组织中IGF-Ⅰ R的表达情况,分析其与NAC疗效之间的关系.[结果]IGF-Ⅰ R阳性率为42.5％(17/40).IGF-Ⅰ R阴性患者在接受NAC后的PR率为82.6％,高于IGF-Ⅰ R阳性患者(47.1％,P=0.018).对化疗方案进行分层分析,在蒽环类药物组中,IGF-Ⅰ R阴性患者的PR率显著高于IGF-Ⅰ R阳性患者(83.3％ vs 33.3％,P=0.013),而在蒽环联合紫杉类药物组中,IGF-ⅠR表达情况与PR率无关(81.8％ vs 80.0％,P=0.931).[结论]测定IGF-Ⅰ R可以预测乳腺癌NAC的疗效,指导NAC方案的选择.对IGF-Ⅰ R阴性的患者,预计NAC的有效率较高,建议实施NAC,首选蒽环类方案,而对IGF-Ⅰ R阳性的患者,预计NAC的有效率较低,不建议首选NAC,如确需选择NAC,则建议采用蒽环联合紫杉类药物的方案.     

乳腺癌新辅助化疗疗效预测因子的研究进展

目的:探讨乳腺癌新辅助化疗疗效预测领域的研究进展.方法:应用PubMed 及 CNKI数据库系统,以“乳腺癌、新辅助化疗”为关键词,检索2008-01 -2011-06的相关文献,分别获得英文文献1 056条、中文文献260条.纳入标准:1)非综述类文献;2)非动物实验和体外实验;3)研究结果中有关于疗效预测的内容.根据纳入标准,精选其中29篇有代表性的文献进行分析.结果:关于乳腺癌新辅助化疗疗效预测已开展了大量研究,其中以分子分型技术最为实用,基因芯片技术前景良好,但由于费用昂贵等缺点目前尚无法在临床推广,分子生物学指标和肿瘤形态学指标对疗效预测也有一定的作用,影像学技术则无法准确预测疗效.结论:目前尚未找到一个能完全准确预测疗效的指标,故在该领域仍有进一步研究的必要.     

不同生物学标志物对乳腺癌新辅助化疗疗效的预测价值

背景与目的:寻找乳腺癌新辅助化疗疗效预测指标将有助于筛选对化疗敏感的患者,指导个体化治疗.因此,本研究旨在探讨不同生物学标志物对紫杉醇类药物联合蒽环类药物的新辅助化疗方案治疗乳腺癌的疗效预测价值.方法:对160例行4个周期紫杉醇类药物联合蒽环类药物的新辅助化疗方案治疗的乳腺癌患者资料进行回顾性分析.采用免疫组织化学法检测术前肿瘤穿刺标本中雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PgR)、人类表皮生长因子受体2(human epidermal growth factor receptor-2,Her-2)、Topo-Ⅱ和Ki-67蛋白的表达,分析其与临床疗效及病理改变的关系.结果:总临床有效率为85%,其中临床完全缓解为46例(28.8%),部分缓解率为90例(56.3%);病理完全缓解23例.单因素分析发现ER、PgR表达阴性及Her-2过表达均可预测临床完全缓解及病理完全缓解(P＜0.05).多因素分析发现Her-2过表达仍是预测临床完全缓解的独立变量(P=0.011),仅ER阴性为预测病理完全缓解的独立变量(P=0.001).结论:Her-2过表达、ER阴性的患者对紫杉醇类药物联合蒽环类药物的新辅助化疗方案更敏感,可作为该方案的疗效预测参考指标.     

血清MMP-9对局部晚期乳腺癌新辅助化疗疗效的预测

目的 探讨局部晚期乳腺癌新辅助化疗（NCT）前后血清基质金属蛋白酶-9（MMP-9）水平的变化及其对疗效的预测价值。方法 检测本院2012年7月至2013年6月收治的80例Ⅱ～Ⅲ期乳腺癌患者NCT前后的血清MMP-9水平并评价NCT疗效。64例ER、PR阳性乳腺癌患者采用EC-T方案化疗（表阿霉素90mg/m2静滴,d1;环磷酰胺600mg/m2静滴,d1,21天为1周期,共4个周期;序贯多西他赛80mg/m2静滴,d1,21天为1周期,共4个周期）,16例ER、PR阴性者采用TEC方案化疗（多西他赛75mg/m2静滴,d1;表阿霉素75～85mg/m2静滴,d1;环磷酰胺600mg/m2静滴,d1,21天为1周期,共4个周期）。分析血清MMP-9水平与NCT疗效及临床病理特征的关系。结果 80例患者共完成NCT 290个周期,有效率（RR）为78.8％（63／80）,其中获CR 4例,PR 59例。38例（47.5％）临床分期降低。NCT前血清MMP-9阳性组（＞900U／L）和阴性组（≤900U／L）的RR分别为85.2％（46／54）和65.4％（17／26）,差异有统计学意义（P＜0.05）。血清MMP-9水平与乳腺癌化疗前分期、HER-2、ER/PR状态及病理学反应性分级均有关（P＜0.05）。在化疗有效、化疗前分期Ⅲ期、HER-2+、ER+、PR-/+、病理学反应性分级G1～G3和G4～G5及绝经和未绝经的患者中,化疗2个周期后的血清MMP-9水平与化疗前比较明显降低（P＜0.05）。结论 血清MMP-9水平对乳腺癌NCT疗效具有一定的预测价值,可减少NCT的盲目性,有助于制定有效的治疗方案。     

乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用

目的:探讨乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用.方法:收集漯河市中心医院收治的236例接受新辅助化疗患者的临床病理资料,分为Luminal A、Luminal B、Her-2阳性和三阴乳腺癌4种分子分型,分析分子分型与临床病理因素、新辅助化疗疗效及 5 年生存率的相关性.结果:236例患者中,107例(45.3%)为Luminal A亚型,47例(19.9%)为Luminal B亚型,27例(11.4%)为Her-2阳性亚型,55例(23.3%)为三阴乳腺癌亚型.Her-2阳性(25.9%)及三阴乳腺癌亚型(30.9%)的病理完全缓解(pCR)率明显高于Luminal亚型(Luminal A亚型 4.7%及Luminal B亚型 8.5%),差异有统计学意义(P<0.05).与Luminal亚型相比,Her-2阳性及三阴乳腺癌亚型具有更差的5年无病生存和总生存(P<0.01);获得pCR的乳腺癌患者的5年无病生存和总生存明显高于化疗后仍有癌残留的患者(P<0.05).结论:相对于Luminal亚型,Her-2 阳性和三阴乳腺癌亚型对新辅助化疗更为敏感,更易达到pCR;但是Her-2阳性和三阴乳腺癌亚型预后反而更差.     

血浆纤维蛋白原水平与乳腺癌新辅助化疗疗效及预后的相关性

目的:评估血浆纤维蛋白原水平与乳腺癌新辅助化疗患者临床效果和预后的关系。方法:使用Clauss凝固法定量检测188例乳腺癌患者新辅助化疗前外周血中纤维蛋白原水平,根据纤维蛋白原水平将患者分为降低组、正常组或升高组。分析纤维蛋白原水平与病理完全缓解（pCR）的相关性,并进行预后分析。结果:月经状态与血浆纤维蛋白原水平相关（P<0.05）。纤维蛋白原水平是pCR的独立预测因素（P=0.002,95%CI:1.699~9.347）。Kaplan-Meier分析显示血浆纤维蛋白原水平升高组的无病生存期（DFS）和总生存期（OS）缩短（P<0.05）。单因素和多因素生存分析均显示分子分型、肿瘤大小、淋巴结状态、纤维蛋白原水平及pCR是DFS和OS的独立预后因素（P<0.05）。结论:血浆纤维蛋白原水平降低提示预后较好,血浆纤维蛋白原水平可能成为预测局部晚期乳腺癌患者新辅助化疗pCR和预后的生物学标志物。     

残余肿瘤负荷评分在乳腺癌新辅助化疗效果评价中的应用

术前新辅助化疗能降低乳腺癌的临床分期,增加手术适应证,并提高保留乳房率,为治疗乳腺癌提供新的可能。pCR被认为是评价新辅助化疗预后的主要终点,但该评价方式过于简单,且缺乏对术后治疗的指导意义。目前,连续性残余肿瘤负荷(RCB)评分已逐步推广。研究表明该评分能用于评估新辅助化疗与乳腺癌分子分型的关系。笔者就RCB评分在乳腺癌新辅助化疗效果评价中的应用和发展前景进行综述。     

Predictive role of molecular subtypes in response to neoadjuvant chemotherapy in breast cancer patients in Northeast China

Introduction: Breast cancer is increasingly regarded as a heterogeneous disease which can be classified into distinct molecular subtypes with prognostic significance. Materials and methods: ER, PR, HER2 and ki-67 were used to divided 102 breast cancers treated with neoadjuvant chemotherapy ( NCT ) into 4 subtypes: luminal A (ER+,PR+,HER2-, and ki-67 ≤14%), luminal B (ER+, PR+,HER2- and ki-67>14% ; ER+ and/or PR+, HER2+), HER2-overexpression (ER-, PR- and HER2+) and triple-negative (ER-, PR-,and HER2-). Results: Among 102 patients, a pCR was seen in 16 (15.7%) patients. The pathologic complete remission (pC) rates according to different subtypes are as follows: luminal A, 0 of 20 (0.0%), luminal B, 2 of 23 (8.7%), HER2-overexpressio,n 4 of 18 (22.2%), and triple-negative, 10 of 41 (24.4%) (p=0.041). In triple-negative subtype patients, the rates of pCR differed significantly among the 3 chemotherapy regimens with 5.6% (1/18) for CEF (cyclophosphamide, epirubicin and flurouracil), 20.0% (1/5) for TE (docetaxel and epirubicin) and 44.4% (8/18) for TCb (docetaxel and carboplatin) (p=0.024). In locally advanced breast cancer patients, the rates of pCR seem to differ among the 3 chemotherapy regimens with 6.7% (2/30) for CEF, 0.0% (0/8) for TE and 23.1% (6/26) for TCb, but this did not attain statistical significance (p>0.05). Conclusions: Molecular subtypes are good predictors for response to NCT in breast cancer patients in Northeast China. Compared with luminal A tumors, HER2-overexpression and triple-negative subtypes are more sensitive to NCT. For triple-negative breast cancer, we concluded that the TCb combination is a promising NCT regimen. Our results also indicated that the TCb combination is promising for the treatment of locally advanced breast cancer.     

Predictive markers of response to neoadjuvant chemotherapy in breast cancer

Several randomized prospective studies on breast cancer patients have proved the safety of neoadjuvant chemotherapy. These trials have also demonstrated that tumor down staging does indeed improve the eligibility for breast conservative surgery without increasing local recurrence rates with possibly an improved survival. However, complete pathologic remissions are noted in only 3–30% of patients. About 20% of patients do not benefit from different chemotherapy regimens currently in use and are thus subjected to toxic drugs. This often leads to progression of disease and thereby the surgeon may lose a window of opportunity to obtain durable locoregional control of disease. Identification of predictive markers associated with pathologic complete response can help to distinguish patients with high or low probability of a response to treatment so that an individualized treatment plan can be implemented. It could also streamline the development of new alternative regimens for those who are unlikely to benefit from existing drugs. It is expected that a combination of markers will be more informative than a single one. So far, several factors have been studied as predictors for response to cytotoxic treatment, viz., tumor size, hormone (estrogen and progesterone) receptor status, tumor type and differentiation, HER2/cerB-2, tumor proliferation Ki-67, apoptosis related genes p53, bcl-2 and BAX; certain subgroups of breast cancer, and the latest in this category is gene expression profiling. However, in terms of prediction of drug responsiveness, data reported are still very limited.This review aims to discuss the current relevant literature on the subject.     

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.     

乳腺癌新辅助化疗疗效及其与生物标志物检测水平变化的相关性

目的:探讨乳腺癌新辅助化疗疗效及其与生物标志物检测水平变化的相关性。方法:通过对乳腺癌新辅助化疗患者疗效的评估以及空心针穿刺标本和手术标本的免疫组织化学染色比较,分析新辅助化疗疗效与生物标志物改变情况,以及二者的关系、影响因素。结果:在76例新辅助化疗的患者中,达到病理完全缓解（pCR）的患者有14例(18.4%),临床有效率达75.00%。对新辅助化疗疗效的相关因素分析,发现雌激素受体（ER）、孕激素受体（PR）状态与疗效相关（P均<0.05）。进一步对14例达到pCR患者的生物标志物进行分析,ER阴性的患者有10例(71.4%)、PR阴性的患者有9例(64.3%)。对比生物标志物,发现新辅助化疗患者Ki-67改变差异有统计学意义（P＜0.05）,而ER、PR、p53改变情况差异无统计学意义（P均＞0.05）。结论:新辅助化疗具有较高的临床缓解率,新辅助化疗疗效与ER、PR状态有关,ER、PR表达较弱者相对较容易达到pCR,并且新辅助化疗后患者生物标志物只有Ki-67改变。     

The role of neoadjuvant chemotherapy for breast cancer treatment

Neoadjuvant chemotherapy is being used increasingly in the management of patients with breast cancer, especially locally advanced cases. Such treatment is administered with the aim of of reducing the size of the primary tumor to increase the possibility of breast-conserving treatment (BCT). In our series, during the period from May 1995 to December 2000, 86 patients with tumors between 3.1 and 6.0 cm in diameter received epirubicin-based neoadjuvant chemotherapy. There were 55 (64.0%) responders and ultimately 64 patients (74.4%) were treated with BCT. With a median follow-up time of 39 months, 9 patients in the BCT group had developed local recurrence. Long-term follow-up is required to establish whether this procedure is a safe alternative to mastectomy for patients with large breast cancers.     

The role of neoadjuvant chemotherapy for breast cancer treatment

Neoadjuvant chemotherapy has become popular, especially for patients with advanced breast cancer. The pros and cons of neoadjuvant chemotherapy for treating breast cancer patients are reviewed. The advantages of neoadjuvant chemotherapy are 1) overall survival and recurrence-free survival rate are the same as post-operative chemotherapy, 2) serves as an in vivo sensitivity test, 3) increases the rate of breast conserving therapy, 4) facilitates the study of cancer biology. On the other hand, the disadvantages of neoadjuvant chemotherapy are 1) it modifies the stage, 2) treatment delay of PD cases, 3) residual intraductal component may be left behind after breast conserving surgery, 4) there are some cases of over-treatment. Combination chemotherapy is one possible way to increase the pathological CR rate, although the optimal order and cycles have not been determined. To avoid residual cancer cells after breast conserving surgery, the shrinkage pattern should be evaluated by MRI. Core needle biopsy should be performed before neoadjuvant chemotherapy to avoid over-treatment. It is essential to develop more effective regimens and stratify patients based on predictive factors.