【作者】 侯红；

【导师】 谷元廷；

【作者基本信息】 郑州大学 ， 外科学， 2011， 硕士

【摘要】 [目的]研究局部晚期乳腺癌患者应用TEC方案行新辅助化疗((neoadjuvant chemotherapy, NACT)时,ER、PR和HER-2的表达状态与乳腺癌新辅助化疗疗效的相关性,及新辅助化疗对于其表达状态的影响。为乳腺癌新辅助化疗的疗效明确预测指标,有助于预测不同病人对于新辅助化疗的敏感性,指导个体化治疗,提高疗效,避免无效治疗延误病情。[方法]收集郑州大学第一附属医院乳腺外二科2008年8月-2010年9月收治的乳腺癌NACT患者52例,单侧患病,均为女性。患者年龄26-68(平均年龄43.7)岁,中位年龄45岁。NACT前后应用彩色多普勒超声测量和评估乳房肿瘤原发灶及区域淋巴结状态,临床分期参照美国癌症联合委员会(AJCC)2002年版TNM分期。病例均为单发,无乳腺恶性肿瘤手术史及辅助化疗、放疗及内分泌治疗史,所有病例均在行新辅助化疗前1周内由组织学病理确诊,病理类型均为浸润性导管癌。采用统一的NACT治疗方案：多西紫杉醇(75mg/m2)+表柔吡星(50mg/m2)+环磷酰胺(500mg/m2),于每个化疗周期第1天内行静脉滴注,21d/周期,化疗3个周期后据世界卫生组织(WHO)实体瘤疗效标准评估疗效。采用免疫组化S-P法检测52例乳腺癌患者在化疗前后ER、PR及HER-2的表达,观察NACT的临床疗效。运用SPSS17.0统计软件包进行数据的统计分析,应用卡方检验分析ER、PR和HER-2的表达与乳腺癌新辅助化疗疗效的相关性,及新辅助化疗对于其表达的影响。[结果]1.52例患者应用TEC方案行3个周期的新辅助化疗后,35例患者NACT有效,总有效率(RR)为67.3%(35/52)；其中6例(11.5%)获得临床完全缓解(CR),29例(55.8%)获得临床部分缓解(PR)；13例(25.0%)病情稳定(SD)；疾病进展(PD)者有4例(7.7%)。病理评价2例患者(3.8%)获得病理完全缓解(pCR)。2.在新辅助化疗中,ER(-)患者NACT有效率为85.0%(17/20)；ER(+)患者为56.3%(18/32),两组间差异有统计学意义(P<0.05)；PR(-)患者NACT有效率为80%(21/25),PR(+)患者为51.6%(14/27),两组间差异有统计学意义(P<0.05)。因此ER、PR可作为乳腺癌NACT方案敏感性的预测指标。3.52例患者在接受NACT后,HER-2过度表达组临床有效患者16例,占该组的比例约53.3%(16/30)。非过度表达组临床有效患者15例,占该组比例约68.2%(15/22)。非过度表达组临床有效率较过度表达组稍高,但两组间差异无统计学意义(p>0.05)。HER-2的表达状态,对于其疗效,无明显相关。4. NACT前后,ER、PR的表达部分发生变化。化疗前,ER阳性表达者为32例,阴性表达者为20例。NACT后,ER阳性表达者为39例,阴性表达者13例。P<0.05,差异有统计学意义。化疗前,PR阳性表达者为27例,阴性表达者为25例。NACT后,PR阳性表达者31例,阴性表达者为21例。P<0.05,差异有统计学意义。NACT可部分改变激素受体的表达。5.新辅助化疗前后,HER-2的表达部分发生变化。化疗前,HER-2过度表达者为30例,非过度表达者为22例。NACT后,HER-2过度表达者为38例,非过度表达者14例。P>0.05,差异无统计学意义。HER-2的表达不受NACT的影响。[结论]乳腺癌新辅助化疗效果肯定；化疗前ER、PR表达与NACT疗效相关,ER(-)及PR(-)患者在NACT中的获益分别较ER(+)及PR(+)者高；在新辅助化疗前后,ER及PR的表达会发生部分变化,化疗后阳性表达细胞数相对增多；HER-2的表达状态与NACT的疗效没有相关性,新辅助化疗前后,HER-2的表达无明显变化。测定激素受体的表达状态及HER-2表达状态,可部分预测乳腺癌患者对NACT的敏感性,初步指导肿瘤个体化辅助化疗。更多还原

【Abstract】 [Objective]To study the relationship of the expression of ER, PR and HER-2 and the effect of neoadjuvant chemotherapy (NACT) on locally advanced breast cancer and the influence of the expression of ER, PR and HER-2 before and after NACT of breast cancer, while studying the neoadjuvant chemotherapy for patients diagnosed with locally advanced breast cancer. Clearly analysing the successful cases of NACT for breast cancer, can help to predict the sensitivity to NACT for different patients, to direct individual treatment, to enhance efficiency of treatment, to avoid worsening prognosis caused by ineffective treatment.[Methods]Collecting all the information of patients admitted in the second department of breast surgery of the First Affiliated Hospital of Zhengzhou University from Aug 2008 to Sep 2010.They are all female, have single sided breast cancer,with an average age of 43.7 years, in the median age 45 years. Apply Doppler ultrasound and analyse the original location of tumor of breast and condition of regional lymph nodes pre and post NACT. Clinically analyze refer to AJCC of version 2002, part TNM(figure 1). All the cases are single sided, with no history of operation of breast and adjunctive chemotherapy, radiology treatment and endocrine treatment.Line in all cases are confirmed by the Pathological neo-adjuvant one week before the NACT is applied. Pathology category is infiltrating cancer of duct.This group of patients were treated with uniform chemotherapy "TEC". Adopt uniform NACT treatments:, docetaxel (75mg/m2)+Epirubicin (50mg/m2)+cyclophosphamide (500mg/m2), in the first days each chemotherapy cycles, one cycle lasts 21 days.each patients adopt 3 cycles treatments. AFTER NACT, according to the world health organization (WHO) solid tumor response standard assessment the effect of NACT.Using immunohistochemistry S-P method to detect the expression of ER, PR, and HER-2 of breast cancer berore and after the NACT. Using SPSS 13.0 statistical software to analysis the data, then analyze the relationship between these and NACT for breast cancer.[Results]1.52 patients received 3 cycle of NACT directed by programme technology,35 patients reacted positively to NACT, the RR is 67.3%, in which 6 cases achieved clinical complete remission(CR),29 cases achieved partial remission(PR).13 cases achieves stable disease(SD), and 4 cases achieved progressive disease(PD). And 2 cases achieved pCR according to pathological analyzing.2.52 patients received 3 cycle of NACT directed by programme technology,17 patients with ER(-) reacted positively to NACT, the RR in these is 85.0%((17/20); the RR in patients with ER(+) is 56.3%(18/32). There are a significant difference between patients with ER (-) and ER(+)(P<0.05).21 patients with PR (-) reacted positively to NACT, the RR in these is 80.0%(21/25); the RR in patients with PR(+) is 51.6%(14/27). There are a significant difference between patients with PR(-) and PR(+)(P<0.05). To determine the expression of receptors of hormone, can predict the sensitivity to NACT of patients diagnosed with breast cancer partially.3.52 patients received 3 cycle of NACT directed by programme technology,16 patients with HER-2(-) reacted positively to NACT, the RR in these is 68.2% (15/22); the RR in patients with HER-2(+) is 53.3%(16/30). It seems that the patients with HER-2(-) can get more benefit from the NACT.But there do not have a significant difference between patients with HER-2(-) and HER-2(+) (P<0.05).4. The expression of ER and PR partialy change before and after NACT. Before the chemotherapy, there are 32 of these patients with ER(+),20 with ER(-). After the chemotherapy, there are some changes happened.The amount of patients with ER(+) increases to 39,and with ER(-) induced to 13.There are a significant difference between pre and post NACT with the expression of ER. Before the chemotherapy, there are 27 of these patients with PR(+),25 with PR(-). After the chemotherapy, there are some changes happened.The amount of patients with PR(+) increases to 31, and with ER(-) induced to 21. There are a significant difference between pre and post NACT with the expression of PR.5. The expression of HER-2 partialy change before and after NACT. Before the chemotherapy, there are 30 of these patients with HER-2(+),22 with HER-2 (-).After the chemotherapy, the amount of patients with HER-2 (+) increases to 38,and with HER-2 (-) induced to 14. But there do not have a significant difference between pre and post NACT with the expression of HER-2.[Conclusions]NACT for breast cancer is effective. The expression before chemotherapy of ER,PR is related to the efficiency of NACT. The patients with ER(-) and PR(-) get more benefit than those with ER(+) and PR(+) in the process of NACT. The expression of ER and PR partialy change before and after NACT. The amount of positive cells relatively increases after chemotherapy. There is nothing related between the expression of HER-2 and the efficiency of NACT. The expression of HER-2 does not has a significant difference pre and post chemotherapy. To determine the expression of receptors of hormone and HER-2,can predict the sensitivity to NACT of patients diagnosed with breast cancer partially and help to direct the individual adjunctive chemotherapy for breast cancer patients initially.更多还原