乳腺癌患者新辅助化疗疗效因素的相关性研究

目的 新辅助化疗是乳腺癌治疗的重要手段之一.文中讨论乳腺癌术前穿刺活检雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、人表皮生长因子受体(human epidermal growth factor receptor-2,HER-2)表达与新辅助化疗有效率的相关性.方法 采用免疫组化的方法检测40例接受新辅助化疗的乳腺癌患者ER、PR、HER-2表达情况,并观察化疗效果.结果 40例乳腺癌患者中,ER、PR阴性表达率分别为42.5%和52.5%,HER-2过表达率37.5%.ER阳性组与ER阴性组化疗有效率差异有统计学意义(P<0.05),PR阳性组与PR阴性组化疗有效率差异有统计学意义(P<0.05),而HER-2过度表达组与非过度表达组化疗有效率差异无统计学意义(P>0.05).结论 ER阴性、PR阴性的乳腺癌患者可能对化疗更敏感,有可能是新辅助化疗敏感性的预测指标.     

局部进展期乳腺癌不同方案新辅助化疗的临床研究

目的 评价局部进展期乳腺癌的两种不同方案的新辅助化疗的近期疗效及其毒性反应。方法 从2001年1月～2004年1月应用CEF、NEF两种不同化疗方案对68例局部进展期乳腺癌进行新辅助化疗。所有患者完成2个周期的新辅助化疗后评价疗效及毒性反应。结果原发灶有效率CEF、NEF两组分别为47．2％（17／36）和71．9％（23／32）；其中各有1例病理完全缓解者，两组均无进展者。腋窝淋巴结有效率CEF、NEF两组分别为63．9％（23／36）和87．5％（28／32）；新辅助化疗后CEF组有11例（30．6%），NEF组有17例（53．1%）未触及肿大淋巴结。两组均未见Ⅳ度毒性反应，白细胞下降、脱发及胃肠道反应两组程度相似。NEF组出现特有的神经毒性和周围静脉炎。结论 两种不同方案用于局部进展期乳腺癌的新辅助化疗均有较好的近期疗效，毒性反应均可耐受。与CEF组相比，NEF组原发灶和腋窝淋巴结疗效均优于CEF组，而且两组毒性反应相当。     

乳腺癌耐药蛋白基因在乳腺癌中的表达及其与化疗疗效的关系

[目的]探讨乳腺癌患者的乳腺癌耐药蛋白(BCRP)基因表达及其与化疗疗效的关系.[方法]采用半定量逆转录一聚合酶链反应(RT-PCR)的方法检测60例行新辅助化疗CEF方案的女性乳腺癌患者乳腺癌组织的BCRP基因,根据化疗前BCRP基因表达情况,将60例患者分为阳性组及阴性组,比较2组间的疗效,观察BCRP基因表达与化疗疗效的关系.[结果]印例乳腺癌患者中BCRP基因阳性表达17例,阳性表达率为28.3%(17/60).BCRP基因阳性组患者总缓解11例,缓解率(64.7%)明显低于阴性组(93.0%),两组比较差异有显著性意义(P<0.05).[结论]BCRP基因高表达患者采用CEF方案化疗效果较差,BCRP基因的表达水平可以作为预测化疗效果的一个重要参考指标.     

乳腺癌组织p53和HER-2的表达及与蒽环类方案化疗敏感性的相关性

目的 探讨乳腺癌组织p53和HER-2的表达及与蒽环类方案化疗敏感性的关系,为乳腺癌蒽环类化疗药物的个体化选择寻找新的依据.方法 采用S-P免疫组化的方法检测184例乳腺癌组织中p53和HER-2的表达,分析两者的不同表达状态与蒽环类方案化疗敏感性的关系.结果 蒽环类为主的联合化疗方案在p53过表达的乳腺癌患者化疗完全缓解率及有效率分别为18.87%和83.02%,较p53阴性的乳腺癌患者好,在HER-2过表达的乳腺癌患者化疗完全缓解率及有效率分别为13.11%和85.25%,较HER-2阴性乳腺癌患者好,差异均有统计学意义(P＜0.05).结论 乳腺癌组织中p53和HER-2过表达可作为蒽环类为主化疗有效的预测因子.     

新辅助化疗对乳腺癌雌激素受体和P53基因及人表皮生长因子受体-2的影响及意义

目的 探讨雌激素受体(ER)和P53基因、人表皮生长因子受体-2(HER-2)在新辅助化疗乳腺癌组织的表达及临床意义.方法 采用免疫组织化学方法检测100例乳腺癌患者新辅助化疗前后肿瘤组织中ER、P53基因及HER-2的表达,分析其与疗效的关系.结果 新辅助化疗总有效率为79%,新辅助化疗前ER、P53基因阳性表达和阴性表达患者化疗后有效率比较,差异均有统计学意义(P＜0.05).而新辅助化疗前HER-2阳性表达和阴性表达患者化疗后有效率比较,差异无统计学意义(P＞0.05).新辅助化疗前后ER、P53基因和HER-2表达率比较,差异均无统计学意义(P＞0.05).结论 新辅助化疗对ER、P53 基因及HER-2表达状态无显著影响;ER和P53 基因对乳腺癌新辅助化疗疗效有一定预测价值.     

术前ET与CEF新辅助化疗方案治疗乳腺癌的临床观察

目的 比较两种不同新辅助化疗方案治疗乳腺癌的疗效及不良反应.方法 46例Ⅱ、Ⅲ期乳腺癌患者随机分为ET组和CEF组,每组23例,分别用ET、CEF化疗方案治疗,3周为1个周期.所有患者完成3周期新辅助化疗后评价疗效.结果 乳腺癌总有效率(OR)ET组为87.0%(20/23),CEF组为61.0%(14/23).两组之间有显著性差异(P＜0.05).主要不良反应恶心、呕吐、厌食、脱发两组相似,ET组骨髓抑制并伴有关节肌肉疼痛及神经毒性.结论 两组新辅助化疗方案对乳腺癌的原发肿瘤均有效,不良反应均可耐受.ET组疗效及不良反应均高于CEF组.     

乳腺癌新辅助化疗的疗效评价及对ER、PR表达的影响

目的 比较T方案和CEF方案新辅助化疗治疗Ⅱ、Ⅲ期乳腺癌的疗效,并探讨其对激素受体表达的影响.方法 选取94例乳腺癌患者,随机分成两组,接受两种方案新辅助化疗,完成4个周期后评价两组疗效,并用免疫组化SP法检测新辅助化疗前后激素受体的表达.结果 Ⅱ期乳腺癌T组的有效率为90.9%,CEF组的有效率为86.2%,两组差异无统计学意义(P>0.05).Ⅲ期乳腺癌T组的有效率为85.7%,CEF组的有效率为61.5%,两组差异有统计学意义(P<0.05).新辅助化疗后ER和PR表达发生改变的分别为Ⅱ例、20例,前后表达改变有统计学意义(P<0.05).结论 T方案和CEF方案新辅助化疗治疗Ⅱ期乳腺癌疗效基本一致,但治疗Ⅲ期乳腺癌前者明显好于后者,且新辅助化疗后可以提高ER、PR的阳性率.     

乳腺癌ER,PR和HER-2的表达状况与新辅助化疗疗效的临床观察

目的探讨乳腺癌组织中ER,PR和HER-2的表达状况与新辅助化疗疗效的关系。方法我院2007-06～2009-07经空芯针活检组织学确诊的乳腺癌患者143例,进行新辅助化疗,均采用TAC方案进行化疗,21d为一个疗程,进行2-4个疗程后观察疗效。结果新辅助化疗总有效率77.6%,临床完全缓解（cCR）31.5%,部分缓解（PR）46.1%,疾病稳定（SD）22.4%,疾病进展（PD）0例,病理完全缓解（pCR）10.5%;单因素分析发现：ER阴性患者的有效率90.0%,ER阳性患者的有效率71.0%,PR阴性患者的有效率88.7%,PR阳性患者的有效率71.1%,ER阴性组与ER阳性组、PR阴性组与PR阳性组化疗有效率差异均有统计学意义（P〈0.05）。HER-2过度表达组有效率75.8%,HER-2非过度表达组有效率78.2%,二者之间差异无统计学意义（P〉0.05）。结论 ER,PR阴性的乳腺癌患者对化疗更敏感,新辅助化疗后获益更多,ER,PR可作为乳腺癌新辅助化疗敏感性的预测指标。     

乳腺癌组织P53和HER-2的表达及与蒽环类方案化疗敏感性的相关性研究

目的：探讨乳腺癌组织P53和HER-2的表达及与蒽环类方案化疗敏感性的关系，为乳腺癌蒽环类化疗药物的个体化选择寻找新的依据。方法：采用S-P免疫组化的方法检测184例乳腺癌组织中P53和HER-2的表达，分析乳腺癌组织P53和HER-2的不同表达状态与蒽环类方案化疗敏感性的关系。结果：蒽环类为主的联合化疗方案在P53过表达的乳腺癌患者化疗完全缓解率及有效率分别为18.87%和83.02%，较P53阴性的乳腺癌患者更好，在HER-2过表达的乳腺癌患者化疗完全缓解率及有效率分别为13.11%和85.25%，较HER-2阴性乳腺癌患者更好，差异均有统计学意义（P<0.05）。结论: 乳腺癌组织中P53过表达和HER-2过表达可作为蒽环类为主化疗有效的预测因子。     

新辅助化疗对乳腺癌ER、PR、HER-2 表达和状态的影响

目的 探讨新辅助化疗对乳腺癌雌激素受体(ER),孕激素受体(PR)、HER-2表达和状态的影响.方法 应用免疫组化方法检测新辅助化疗组和对照组(为新辅助化疗组)的乳腺癌患者手术前后ER,PR、HER-2的表达及表达状态变化的差异.结果 化疗组、对照组ER表迟强度发生改变分别为27.59%(16/58),8.62%(5/58).两组比较差异有统计学意义(P<0.05),两组ER状态改变无统计学意义(P>0.05);化疗组、对照组PR表达强度发生改变分别为18.97%(11/58)、13.79%(8/58),两组比较无统计学意义(P>0.05),两组PR状态改变亦无统计学意义(P>0.05);化疗组、对照组HER-2表达强度发生改变分别为12.07(7/58),6.90%(4,58),两组比较无统计学意义(P>0.05).结论 新辅助化疗能使部分乳腺癌组织中ER表达强度发生改变,但影响ER状态,而新辅助化疗对乳腺癌PR,HER-2表达无影响.     

不同方案新辅助化疗对乳腺癌激素受体表达的影响

目的 探讨不同方案新辅助化疗对乳腺癌激素受体表达的影响.方法 免疫组化检测不同方案新辅助化疗组的乳腺癌患者化疗前后肿瘤组织雌激素受体(estrogen receptor,ER)和孕激素受体(progesterone receptor, PR)的表达情况,并比较两组化疗前后ER和PR表达水平的差异.结果 TE方案新辅助化疗组60例,ER表达水平增强15例(25.0%),减弱8例(13.3%),PR表达水平增强12例(20.0%),减弱6例(10.0%);CEF方案新辅助化疗组57例,ER表达水平增强8例(14.0%),减弱4例(7.0%),PR表达水平增强6例(10.5%),减弱3例(5.3%).TE方案新辅助化疗前后ER、PR表达水平改变显著(P＜0.05),而CEF方案新辅助化疗前后改变不显著(P＞0.05),不同疗效病例组之间ER、PR的表达水平改变差异显著(P＜0.05).结论 TE方案新辅助化疗对乳腺癌患者的ER、PR表达水平的改变影响显著,而CEF方案新辅助化疗对乳腺癌患者ER、PR表达水平的改变无明显影响,化疗后ER、PR表达水平的改变与疗效有关.     

乳腺癌新辅助化疗前检测雌激素受体和孕激素受体的临床意义

目的探讨新辅助化疗对乳腺癌组织中雌激素受体（ER）和孕激素受体（PR）表达的影响以及新辅助化疗前后测定ER、PR的必要性。方法2000年1月至2008年1月对231例Ⅱ～Ⅲ期局部晚期乳腺癌进行CMF、CAF或CTF、AT等不同方案进行新辅助化疗,在化疗前后分别进行ER和PR的检测,以了解新辅助化疗前后ER和PR的变化。结果ER新辅助化疗前阳性表达率为44．39％,新辅助化疗后的阳性表达率为63．23％,其差异有统计学意义（X^2=9．824,P〈0．05）。PR新辅助化疗前阳性表达率为60．99％,新辅助化疗后的阳性表达率为60．09％,其差异无统计学意义（X^2=3．526,P〉0．05）。结论由于新辅助化疗对部分ER、PR的表达有影响,且与化疗疗效有关,所以必须在对所有实施新辅助化疗的乳腺癌患者实施化疗前后ER、PR的测定,为以后的综合治疗提供必要的依据。同时认为TA方案优于CAF或CTF方案,CAF或CTF方案又优于CMF方案。     

新辅助化疗对乳腺癌雌、孕激素受体和HER-2的影响

OBJECTIVE: To study the effect of neoadjuvant chemotherapy on estrogen receptor (ER), progesterone receptor (PR), and HER-2 expression in patients with breast cancer. METHODS: From 59 breast cancer patients treated with neoadjuvant chemotherapy and 33 without neoadjuvant therapy (control), core biopsy samples before the chemotherapy or surgery and surgical specimens were obtained for assay of ER, PR, and HER-2 expression. RESULTS: Quantitative alteration of ER expression occurred in 37.29% (22/59) of the patients after neoadjuvant chemotherapy and in 15.15% (5/33) of the control patients, showing statistically significant difference between the two groups (P<0.05), but the changes in ER expression status (conversion between positivity/negativity ratio) exhibited no significant difference. After the surgery, quantitative changes in PR expression was noted in 23.73% (14/59) of patients with neoadjuvant chemotherapy, without significant difference from those in the control group or changes in the expression status. Similarly, the changes in HER-2 expression seen in 13.56% (8/59) of the patients with chemotherapy was also comparable with the control group, without significant changes in the expression status. CONCLUSIONS: Significant changes occur in ER receptor expression after neoadjuvant chemotherapy in patients with breast cancer, but such changes do not affect the ER status. Neoadjuvant chemotherapy has no significant effects on PR and HER-2 expression in breast cancer patients.     

新辅助化疗对乳腺癌雌、孕激素受体和HER-2的影响

目的探讨新辅助化疗对乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)和HER-2表达的影响。方法2001年8月~2003年12月共有92例手术的乳腺癌患者进入本研究,其中新辅助化疗者59例作为化疗组,未行新辅助化疗者33例作为对照组。分析并比较两组患者术前活检标本和术后大体标本瘤组织中ER、PR和HER-2表达和表达状态变化的差别。结果化疗组术后有37.29%(22/59)患者的ER表达出现量变,对照组为15.15%(5/33),两组比较有显著性差异(P<0.05);两组ER状态改变无显著差异。化疗组术后有23.73%(14/59)患者的PR表达出现量变,但与对照组比较无显著性差异。化疗组术后有13.56%(8/59)患者HER-2表达出现变化,但与对照组比较无显著性差异。结论新辅助化疗能使部分乳腺癌组织中ER表达发生量变,但很少影响ER状态,而新辅助化疗对乳腺癌PR和HER-2表达无影响。     

ER、PR、HER-2、Ki-67与乳腺癌新辅助化疗疗效相关性分析

目的  探讨雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）、Ki67抗原（Ki-67）与乳腺癌新辅助化疗疗效相关性分析。方法  采用免疫组织化学方法检测81例乳腺癌新辅助化疗前后ER、PR、HER-2、Ki-67的表达情况,并评估其与乳腺癌新辅助化疗有效率的关系。结果  81例患者中临床RR79％,术后pCR（9.9％）,tpCR（6.2％）。达到pCR+tpCR率,（ER阴性）23.0%>（ER阳性）12.7%,（PR阴性）28.6%>（PR阳性）9.4%;ER、PR、HER-2及Ki67等与新辅助化疗疗效之间差异无统计学意义。新辅助化疗前后ER、PR、HER-2的状态改变不明显,差异无统计学意义（P >0.05）,而Ki67的表达数量有统计学意义（P <0.05）,其降低了Ki67的表达水平。结论  乳腺癌新辅助化疗可有效控制肿瘤,ER或PR阴性者较阳性者可获得更高的pCR+tpCR率,Ki67可作为化疗药物敏感性和耐药性的预测指标。

     

HER2 and topoisomerase Ⅱα： possible predictors of response to neoadjuvant chemotherapy for breast cancer patients

Background Surrogate markers may be used to assess the response to neoadjuvant treatment. The association between HER2 overexpression and favorable response to specific therapy in breast cancer is controversial, and the mechanism unclear. The purpose of the study was to evaluate HER2 and topoisomerase Ⅱα （Topo Ⅱα） as candidates for predicting the response to neoadjuvant chemotherapy in breast cancer patients.
Methods Between 1999 and 2006, seventy-six breast cancer patients who had received neoadjuvant chemotherapy were studied. Regimens including either CEF （cyclophosphamide, epirubicin, 5-fluorouracil） or CMF （cyclophosphamide, methotrexate, 5-fluorouracil） were given in more than three cycles to this group of patients. Protein expression of HER2 and Topo Ⅱα were determined by immunohistochemistry. The primary endpoint was pathological and clinical response.
Results Of 76 primary breast cancer samples, 27 （35.5%） showed overexpression of either HER2 （25%） or Topo Ⅱα protein （10.5%）, whereas in 7 tumors （9.2%） both proteins were found to be overexpressed. Ten patients （13.2%） had a clinical complete response and 21 （27.6%） had a clinical partial response. Five women （6.6%） had a pathological complete response, 5 （6.6%） had microscopic residual disease, and 46 （60.5%） had macroscopic residual disease. HER2 and Topo Ⅱα overexpression was significantly associated with a favorable response （P 〈0.001 and P=0.005 respectively）.
Conclusion Our study suggests that HER2 and Topo Ⅱα overexpression could be predictors of the response to neoadjuvant chemothrapy in both the CEF and CMF arms.     

乳腺癌对吡柔比星和表柔比星的药物敏感性及有效性的对比观察

目的 通过检测原代乳腺癌细胞对吡柔比星和表柔比星的药物敏感性,来综合评估吡柔比星用于乳腺癌辅助化疗的可行性.方法 收集2008年1月至2009年1月天津医科大学附属肿瘤医院乳腺科就诊的129例原发性乳腺癌患者的新鲜肿组织,采用胶原凝胶体包埋肿瘤细胞原代培养法培养原代乳腺痛细胞,检测其对吡柔比星和表柔比星的敏感性;并同时将139例Ⅱ b～Ⅲ C期原发性乳腺癌患者随机分为两组,分别采用TAC(多西他赛+吡柔比星+环磷酰胺)方案及TEC(多西他赛+表柔比星+环磷酰胺)方案进行4～6周期的新辅助化疗,并观察肿瘤大小、腋窝淋巴结的变化及毒副反应.通过回顾性分析2003至2006年收治的1241例乳腺癌患者的病例资料,根据患者所应用的化疗方案,将其分为CAF(环磷酰胺+吡柔比星+氟尿嘧啶)组及CEF(环磷酰胺+表柔比星+氟尿嘧啶)组,比较两组患者的远期预后.结果 原代乳腺癌细胞对吡柔比星和表柔比星的药物敏感性差异无统计学意义(P=0.743);新辅助化疗总有效率为87.8%,TAC组和TEC组的总有效率、病理完全缓解率、临床完全缓解率、临床部分缓解率以及病情稳定率差异均无统计学意义(均P>0.05).化疗过程中两组白细胞下降、血小板减少、便秘、心脏毒性、肝肾功能异常方面差异均无统计学意义(均P>0.05).仅TAC组胃肠道反应(恶心或呕吐)为46.5%,低于TEC组的66.2%(P=0.019):CAF组与CEF组5年无病生存率分别为79%、78%,5年总生存率分别为85%、82%,两组患者的无病生存期及总生存期差异均无统计学意义(均P>0.05).结论 吡柔比星及表柔比星在药物敏感性检测方面、乳腺癌新辅助化疗疗效和毒副反应方面、乳腺癌治疗的远期疗效方面差异均无统计学意义,吡柔比星可以与表柔比星一样用于乳腺癌辅助化疗的一线药物.

Abstract：

Objective To compare the chemosensitivity of pirarubicin(THP)and epimbicin (EPI)in primary breast cancer(PBC)cells so as to examine tIleir difierential chemosensitivity to THP and EPI by CD-DST(collagen gel droplet embedded culture-drug sensitivity test)system;To detect the differences in the short.term clinical efficacy and side effects between TAC(docetaxel+pirarubicin+cyclophosphamide)and IEC(docetaxel + epirubicin + cyclophosphamide)as the neoadjuvant chemotherapy regimens and the long-term clinical efficacy of CAF ( cyclophosphamide+pirarubicin+fluoroumcil)and CEF(cyclophosphamide+epirubicin+fluorouracil)as the chemotherapy regimens in breast callcer:To evaluate the feasibility of THP as an adjuvant chemotherapeutic regimen in the treatment of breast cancer.Methods From January 2008 to January 2009,a total of 129 fresh breast cancer samples were collected. The differential chemosensitivity of cultured PBC cells to THP and EPI was measured by CD-DST test. And 139 cases of PBC patients in II b-Ⅲ c phase were randomly divided into two groups: TAC and TEC groups. After 4-6 cycles of neoadjuvant chemotherapy, the primary lesion, axiltary lymph nodes and side effects were assessed; The clinical data and survival status of 1241 cases of PBC patients treated at our hospital from 2003 to 2006 were collected and divided into CAF and CEF groups according to their chemotherapeutic regimens. Long-term prognosis was compared between two groups. Results There was no significant difference of chemosensitivity between THP and EPI in PBC cells ( P = 0. 743 ) ; The overall response rate (RR) of neoadjuvant chemotherapy was 87.8% ; there was no significant difference between TAC and TEC groups (P > 0.05 ). No significant differences existed between two groups in such side effects as leukopenia, thrombocytopenia, constipation, cardiotoxity and hepatorenal dysfunction (P > 0. 05 ). The gastrointestinal reactions of nausea and vomiting was less frequent in the TAC group than that in the TEC group (46. 5% vs 66. 2% , P =0. 019) ; There was no significant difference in 5-year disease-free survival rate (79% vs 78% ) and overall survival rate between two groups (85% vs 82%, P >0. 05). Conclusions There were no significant differences in chemosensitivity, clinical efficacy of neoadjuvant chemotherapy, side effects or long-term efficacy between THP and EPI. Both pirarubicin and epirubicin may be used as conventional chemotherapy in breast cancer.     

Role of TMS5: staphylococcal multidrug-efflux protein QacA

Background Neoadjuvant chemotherapy provides an excellent model for evaluation of potential predictive factors. The objective of this study was to evaluate the predictive value of different biological factors in breast cancer patients treated with neoadjuvant taxane and anthracycline chemotherapy. Methods One hundred and thirty-five patients treated with 4 cycles of neoadjuvant taxanes and anthracycline were included in this retrospective study. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor （ER）, progesterone receptor （PgR）, HER-2, Ki-67 and p53 protein expression. The associations among biological markers and clinical and pathological complete response （pCR） were analyzed. Results The overall clinical response was 86%, including 33% clinical complete response （cCR） and 53% clinical partial response. The pCR was just 17%. In the univariate analysis, only HER-2 overexpression was predictive of cCR to neoadjuvant chemotherapy （P=-0.018）. No significant associations between other biological factors and cCR were found. Absence of ER, PgR expression and overexpression of HER-2 were predictive of the pCR （P=0.002, 0.001, 0.01, respectively）. Ki-67 and p53 failed to show an association with pCR. In multivariate analysis, overexpression of HER-2 remained as an independent variable in predicting the cCR （P=-0.021）. However, negative ER was the only parameter that maintained statistical significance in predicting the pCR （P=-0.001）. Conclusions Patients with overexpression of HER-2 and negative hormonal receptor status are much more likely to respond to neoadjuvant taxane and anthracycline chemotherapy than those with the opposite characteristics. These factors could serve as predictive markers for this regimen.