乳腺癌新辅助化疗预测因子的研究进展

乳腺癌新辅助化疗预测因子的研究对乳腺癌患者选择敏感的化疗方案和避免不合适的化疗方案具有重要作用.目前,雌激素受体(ER)、孕激素受体(PR)和HER-2是乳腺癌新辅助化疗的主要预测因子.其他预测因子如Ki-67等将在未来乳腺癌新辅助化疗方案选择中显示出巨大的价值.     

乳腺癌生物学特性预测新辅助化疗敏感性的研究现状

化疗包括术前化疗(新辅助化疗)和术后化疗,是乳腺癌综合治疗的重要组成部分,然而并非所有患者对化疗敏感。近年来,有研究指出,除肿瘤细胞本身以外,肿瘤间质成分的特性也会影响新辅助化疗的疗效。这些特性包括局部免疫细胞、基质成纤维细胞以及肿瘤蛋白、基因组学指标等。相关研究为新辅助化疗方案的选择及提高疗效提供了新的途径。本文就这些方面进行了系统文献复习和总结。     

乳腺癌新辅助化疗预测因子的研究进展

乳腺癌新辅助化疗预测因子的研究对乳腺癌患者选择敏感的化疗方案和避免不合适的化疗方案具有重要作用.目前,雌激素受体(ER)、孕激素受体(PR)和HER-2是乳腺癌新辅助化疗的主要预测因子.其他预测因子如Ki-67等将在未来乳腺癌新辅助化疗方案选择中显示出巨大的价值.     

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.     

磁共振功能成像预测乳腺癌新辅助化疗疗效的研究进展

正乳腺癌是一个在世界范围内严重危害女性健康的恶性肿瘤。近20年来,全球乳腺癌发病率以3.1%的速度递增,已跃居女性恶性肿瘤发病率的首位。国际癌症研究机构(International Agencyfor Research on Cancer,IARC)最新公布的数据表明,2008年全球约有138万乳腺癌新发病例,在西欧,其发病率高达89.7/10万。在我国,上海乳腺     

乳腺癌新辅助化疗进展

新辅助化疗是在除外转移情况下,在局部治疗前（手术或放疗）进行的全身化学药物治疗。尽管目前研究表明同方案的新辅助与辅助化疗相比并不能改善总生存率,仅在达到病理完全缓解（pCR）的患者能获得生存优势,但其能使原发肿瘤和区域淋巴结降期,提高保乳手术率,而且新辅助化疗可以预测个体对化疗方案敏感性。文章对近几年的新辅助化疗在乳腺癌的分子分型和化疗敏感性、优化化疗的方案用法和疗程,其它治疗模式与化疗的联合、pCR的本质意义等方面进一步讨论。     

Ⅲ期乳腺癌新辅助化疗40例

 目的　观察Ⅲ期乳腺癌新辅助化疗的临床疗效。方法　对2004年2月至2007年2月收治的40例Ⅲ期乳腺癌进行新辅助化疗，采用TE方案：表柔比星（EPI）60 mg／m2，第1天，紫杉醇（TAX） 150 mg／m2，第2天，21 d为1个周期，共3 ~ 4个周期。结果　CR 11例，PR 25例，NC 4例，PD 0例，总有效率为90 %，其中pCR率为12.5 %，有52.5 %的患者分期降低，新辅助化疗结束后40例全部进行了手术治疗，其中改良根治术36例，根治术3例，扩大根治术1例。结论　新辅助化疗可以使原发肿瘤缩小，降低肿瘤分期，为手术创造机会。     

Ⅲ期乳腺癌新辅助化疗20例临床观察

20例Ⅲ期乳腺癌进行新辅助化疗,化疗方案为CAF或CEF,疗程均为3个周期,术后再根据病情和术前化疗结果辅以放疗及辅助化疗。原发灶PR16例(16/20),SD4例(4/20),有效率80%。腋窝淋巴结CR1例,PR18例,有效率95%。术后随访4~35个月,平均12个月,无死亡病例。     

乳腺癌新辅助化疗初探

目的 探讨乳腺癌新辅助化疗的临床使用价值及适应证。方法 40例各期乳腺癌患者接受新辅助化疗,手术前接受3个疗程化疗,方案以NF为主,其中5－氟脲嘧啶（5－Fu）500mg/m^2、去甲长春花碱（NVB）25mg/m^2,肿瘤＞53者加用表阿霉素（EPI）40mg/m^2,化疗中白细胞低下者使用集落刺激因子（G－CSF）75μg皮下注射,每日1次至正常。手术后化疗根据病情和术前化疗结果而定。结果 新辅助化疗总体有效率95．0％,术前化疗达到临床完全缓解3例,占7．5％,部分缓解35例,T3、T4各有1例无效。术后随访4－37个月,平均20个月,无死亡病例,4例出现局部复发或转移。结论 新辅助化疗术前以3个疗程为宜,最大受益者是原本不可手术病例以及部分拟行保乳手术病例。     

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.     

Metabolomics approach for predicting response to neoadjuvant chemotherapy for breast cancer

Breast cancer is a clinically heterogeneous disease, which necessitates a variety of treatments and leads to different outcomes. As an example, only some women will benefit from chemotherapy. Identifying patients who will respond to chemotherapy and thereby improve their long-term survival has important implications to treatment protocols and outcomes, while identifying non responders may enable these patients to avail themselves of other investigational approaches or other potentially effective treatments. In this study, serum metabolite profiling was performed to identify potential biomarker candidates that can predict response to neoadjuvant chemotherapy for breast cancer. Metabolic profiles of serum from patients with complete (n = 8), partial (n = 14) and no response (n = 6) to chemotherapy were studied using a combination of nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography–mass spectrometry (LC–MS) and statistical analysis methods. The concentrations of four metabolites, three (threonine, isoleucine, glutamine) from NMR and one (linolenic acid) from LC–MS were significantly different when comparing response to chemotherapy. A prediction model developed by combining NMR and MS derived metabolites correctly identified 80% of the patients whose tumors did not show complete response to chemotherapy. These results show promise for larger studies that could result in more personalized treatment protocols for breast cancer patients.     

Tau expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy

The purpose of this study was to investigate the correlation between tau expression in primary breast cancer and sensitivity to taxanes during neoadjuvant chemotherapy in patients with breast cancer. We used immunohistochemistry to examine tau expression in breast cancer biopsies from 113 primary breast cancer patients and evaluated the correlation between tau expression and taxane sensitivity. Twenty-eight (24.78 %, 28/113) patients were positive for tau expression. After taxanes-based neoadjuvant chemotherapy, 40 patients achieved pathological complete response (pCR) (35.4 %). Among the 40 patients with pCR, five (12.5 %) were positive for tau expression. In univariate analysis, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), and tau were found to be significantly predictive of a pCR (P?=?0.001, 0.030, 0.002, and 0.025, respectively). Tau, ER, and HER2 status were significant for pCR on multivariate analysis (P?=?0.025, 0.005, and 0.043, respectively). Tau expression was positively related to ER (P?=?0.007) and progestin receptor (P?=?0.008). In conclusion, tau protein expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy; patients negative for tau expression were more likely to achieve pCR.     

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。     

声脉冲辐射力成像技术评价乳腺癌新辅助化疗疗效的价值研究

目的 探讨声脉冲辐射力成像技术(ARFI)在乳腺癌新辅助化疗疗效评价中的应用价值.方法 选取42例原发性浸润性乳腺癌患者(共42个病灶),所有患者均于新辅助化疗后行外科手术治疗.应用ARFI技术测量新辅助化疗前后病灶最大弹性值变化率.以Millen-Payne(MP)分级系统作为病理反应的评价依据,Ⅰ~Ⅲ级为组织学非显著反应,Ⅳ~Ⅴ级为组织学显著反应.以手术病理诊断为金标准,应用受试者工作特征曲线(ROC)评价ARFI的诊断价值.结果 42例乳腺癌组织中,69.05%(29/42)为组织学显著反应,30.95%(13/42)为组织学非显著反应.通过ROC曲线确定的评价新辅助化疗有效和无效的VTQ值变化率诊断界值为29%(曲线下面积为0.925,95%CI:0.863~0.987),敏感度为91.1%,特异度为83.3%,准确度为87.7%.新辅助化疗后,组织学显著反应组乳腺癌患者的VTQ值(弹性值)明显低于化疗前,差异有统计学意义(P﹤0.01).结论 ARFI技术可通过定量测量新辅助化疗前后乳腺癌硬度变化,为乳腺癌新辅助化疗的疗效评估提供新方向.     

乳腺癌分子分型对多西他塞联合表柔比星新辅助化疗疗效的预测价值

目的探讨乳腺癌分子分型对多西他塞联合表柔比星新辅助化疗(TE-NAC)疗效的预测价值。方法选取2013年1月至2014年12月间青岛市中心医院收治的128例乳腺癌患者,于化疗前后进行免疫组化分析,按照分子分型结果分为A组(Luminal A型)、B组(Luminal B型)、C组(Her-2型)和D组(Basal-like型)四组。比较四组患者临床疗效,并对四组疗效行多因素Cox回归分析。结果四组患者年龄、病灶直径、肿瘤分期临床分期和区域淋巴结等差异无统计学意义(P>0.05)。A组、B组、C组和D组病理完全缓解率(pCR)分别为12.1%、10.8%、37.5%和75.0%,有效(RR)率分别为45.5%、59.0%、87.5%和100.0%,差异均有统计学意义(均P<0.05)。A组、B组、C组和D组患者无瘤生存率分别为75.8%、69.9%、37.5%和25.0%,患者3年总生存率分别为81.8%、80.7%、50.0%和25.0%,四组患者无瘤生存率和总生存率比较,差异有统计学意义(P<0.05)。多因素Cox回归分析,乳腺癌分子亚型为NAC疗效的独立影响因素。结论乳腺癌分子分型可以作为TE-NAC疗效的预测指标。     

Determining the morphological features of breast cancer and predicting the effects of neoadjuvant chemotherapy via diagnostic breast imaging

Background Neoadjuvant chemotherapy has recently become common therapy for breast cancer. This work studied whether or not the effects of neoadjuvant chemotherapy can be predicted from morphological features of breast cancer in initial diagnostic imaging. Materials and methods A total of 186 cases who underwent neoadjuvant chemotherapy at this hospital in 2006 were studied. Morphological features were classified into four categories. One is a type of invasive carcinoma that tends to grow along the mammary ducts (type A1), another is a type of expansively growing invasive carcinoma that is relatively well-defined (type A2), a third is a type of irregularly shaped mass that retracts surrounding tissue (type A3), and the fourth is a mixed type. Thus, the effects of neoadjuvant chemotherapy on carcinomas of the four types were compared on the basis of image and pathological findings. Effects of neoadjuvant chemotherapy were classified into three categories of enlarged mass, pCR, and other, with the latter indicating no change or shrinkage. Results Of the 186 total cases, 72 were classified as type A1, 31 as type A2, 52 as type A3, and 31 as a mixed type. Seven of 31 cases of type A2 (22.6%) were cases of an enlarged mass, revealing a high percentage of such cases. Dividing cases into type A2 and other types and looking at the proportion of cases of an enlarged mass thus indicated a significantly higher tendency. pCR was achieved in 6 of 31 cases with type A2 (19.4%). Here, also, the proportion of type A2 cases was significantly higher. Conclusion Morphological features prior to neoadjuvant chemotherapy can contribute to determining the effects of the therapy. Expansively growing well-defined masses contain lesions at both extremes, tending to enlarge in some instances or instead allowing pCR, so the course of therapy must be carefully followed when performing neoadjuvant chemotherapy. This article is based on a presentation delivered at Presidential Symposium 1, “Breast cancer: individualized diagnosis for tailored treatment,” held on 29 June 2007 at the 15th Annual Meeting of the Japanese Breast Cancer Society in Yokohama.     

乳腺癌新辅助化疗再认识

近年来随着乳腺癌新辅助化疗研究的深入,该治疗手段已在临床被广泛应用。新辅助化疗使不可手术的局部晚期乳腺癌患者获得手术治疗的机会,并且提高具有较大肿瘤体积患者的保乳率,从而明显改善患者的生存质量,但仍有许多问题存在争议。本文将对乳腺癌新辅助化疗相关临床研究、以及对新辅助化疗的再认识进行综述。