ER、PR及HER-2的表达与乳腺癌新辅助化疗疗效的相关性
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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。
[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.
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。
[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.
引文
[1]费菲,陈灿铭,张斌,等.CTF方案应用于局部晚期乳腺癌新辅助化疗的研究[J].中国肿瘤临床,2009,36(10)：564-567
[2]Straver ME,Glas AM,Hannemann J,et al.The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer[J].Breast Cancer Res Treat,2010,119(3): 551-558
[3]Kumar A,Kumar R,Seenu V,et al.The role of 18F-FDG PET/CT in evaluation of early response to neoadjuvant chemotherapy in patients with locally advanced breast cancer[J].Eur Radiol,2009,19(6):1347-1357
[4]孙燕主编.肿瘤内科手册[M].第3版,北京：人民卫生出版社,1996.30-34
[5]左文述.现代乳腺肿瘤学[M].第2版,济南：山东科学技术出版社,2006.956
[6]Van der Hage JA,van de Velde CJ,Julien JP,et al.Preoprative chemotherapy in primary operable breast cancer;results from the Europen Organization for Research and Treatment of Cancer trial 10902[J].J Clin Oncol,2001,19(22):4224-4237
[7]Mamounas EP,Fisher B.Preoperative (neoadjuvant) chemotherapy in patients with breast cancer[J]. Semin Oncol,2001,28(4):389-399
[8]Nowell PC.The clonal evolution of tumor cell populations[J].Science,1976,194:23-28
[9]Drewinko B,Patehen M,Yang LY,et al.Differential killing efficacy of twenty antitumor drugs on proliferating and nonproliferating human tumor cells[J]. Cancer Res,1981, 41,2328-2333
[10]Grazia Arpino,Heidi Weiss,Adrian V,et al.Estrogen receptor-positive, progester-one receptor-negative breast cancer association with growth factor receptor expression and tamoxifen resistance[J].J National Cancer Institute,2005,97(17):1254-1261
[11]钟源,江学庆,尹美蓉,等.原癌基因C-erbB-2在乳腺癌中的表达及其临床意义[J].中国普通外科杂志,2008,17(5)：502-503
[12]王夫景,李刚,杨维良,等.乳癌p53与雌、孕激素受体的表达及临床意义[J].中国普通外科杂志,2002,6(11)：363-364
[13]于冰,丁锦辉,王闽全,等.乳腺浸润性导管癌中ER,PR,c-erbB-2, p53和nm23的表达及对预后的多因素分析[J].中国普通外科杂志,2007,16(11)：1118-1120
[14]Lehmann U,Glockner S,Kleeberger W,et al. Detection of gene amplification in archival breast cancer specimens by laserassisted microdissection and quantitative real-time polymerase chain reaction[J].Am J Pathol,2000,156:1855-1864
[15]张敏.乳癌含量测定及其预后关系[J].当代肿瘤病学,1994,1(1)：27-28
[16]McClelland RA,Gee JM,O'Sullivan L,et al.p21(WAF1) expression and endocrine response in breast cancer [J].J Pathol,1999,188(2):126-132
[17]沈镇宙,邵志敏.乳腺肿瘤学[M].上海：上海科学技术出版社,2005：147
[18]Bear HD,Anderson S, Smith RE,et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27[J]. J Clin Oncol,2006, 24(13):2019-2027
[19]Ogston KN, Miller ID, Schofield AC, et al. Can patients'likelihood of benefiting from primary chemotherapy for breast cancer be predicted before commencement of treatment? [J].Breast Cancer Res Treat,2004,86(2):181-189
[20]Fisher ER,Wang J,Bryant J,et al.Pathobiology of preoperative chemotherapy:findings from the National Surgical Adjuvant Breast and Bowel Project(NSABP) Protocol B-18[J]. Cancer,2002,95:681-695
[21]王丕琳,李玉文,尹子毅,等.表柔比星联合紫杉醇对浸润性导管癌新辅助化疗临床研究[J].中华肿瘤防治杂志,2007,14(9)：698-700
[22]刘伟平,臧家兰,蔡莉.乳腺癌生物学因子与新辅助化疗疗效的相关性分析[J].放射免疫学杂志,2009,22(1)：82-85
[23]Jain V, Landry M,Levine EA.The stability of estrogen and progesterone receptors in patients receiving preoperative chemotherapy for locally advanced breast carcinoma [J]. Am Surg,1996,62(2):162-165
[24]Lee SH, Chung MA,Quddus MR,et al.The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression and hormonal receptor status in breast cancer[J]. Am J Surg,2003,186(4):348-350
[25]Makris A, Powles TJ,Allred DC,et al.Quantitative changes in cytological molecular markers during primary medical treatment of breast cancer:a pilot study[J].Breast Cancer Res Treat,1999,53(1):51-59
[26]王殊,张嘉庆,乔心民,等.新辅助化疗对乳腺癌雌孕激素受体表达的影响[J].中华外科杂志,2005,15(43)：1011-1013
[27]Piper GL,Patel NA,Patel JA,et al.Neoadjuvant chemotherapy for locally advanced breast cancer results in alterations in preoperative tumor marker status[J].Am Surg.2004,70(12): 1103-1106
[28]Taucher S,Rudas M,Gnant M,et al.Sequential steroid hormone receptor measurements in primary breast cancer with and without intervening primary chemotherapy[J].Endocr Relat Cancer,2003,10(1):91-98
[29]Martin MB,Angeloni SV,Garcia-Morales P,et al.Regulation of estrogen receptor-alpha expression in MCF-7 cells by taxol[J].J Endocrinol,2004,180(3):487-496
[30]Fiegl H,Millinger S,Goebel G, et al.Breast cancer DNA methylation profiles in cancer cells and tumor stroma:association with HER-2/neu status in primary breast cancer [J].Cancer Res,2006,66(1):29-33
[31]Slamon DJ,Clark GM,Wong SG,et al.Human breast cancer:correlation of relapse and survival with amplification of the HER-2/neu oneogene[J].Science,1987,235(4785): 177-182
[32]Muss HB,Thor AD,Berry DA,et al.C-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer[J].N Engl J Med,1994, 330(18):1260-1266
[33]Tulbah AM, Ibrahim EM, Ezzat AA, et al. HER-2/neu overexpression does not predict response to neoadjuvant chemotherapy or prognosticate survival in patients with locally advanced breast cancer [J].Med Oncol,2002,19 (1):15-23
[34]Rozan S,Vincent-Salomon A,Zafrani B,et al.No significant predictive value of c-erbB-2 or p53 expression regarding sensitivity to primary chemotherapy or radiotherapy in breast cancer.[J].Int J Cancer,1998,79(1):27-33
[35]Zhang F,Yang Y,Smith T,et al.Correlation between Her-2 expression and response to neoadjuvant chemotherapy with 5-fluorouracil,doxorubicin,and cyclophosphamide in patients with breast carcinoma[J].Cancer,2003,97(7):1758-1765
[36]Niskanen E,Blomgvist C,Franssila K,et al.Predictive value of C-erbB-2,p53, cathepsin-D and histology of the primary tumour in metastatic breast cancer[J].Br J Cancer,1997, 76(7):917-922
[37]徐美玲,王继见.乳腺癌新辅助化疗疗效预测因子的初步研究.2007年P29
[38]Thor AD,Berry DA,Budman DR, et al.erbB-2,p53,and efficacy of adjuvant therapy in lymph nodepositive breast cancer[J].J Natl Cancer Inst,1998,90(18):1346-1360
[39]Pritchard K1,Shepherd LE,O'Malley FP,et al.HER-2 and responsiveness of breast cancer to adjuvant chemotherapy[J].N Engl J Med,2006,354(20):2103-2011
[40]Gregory RK, Powles TJ, Salter J,et,al.Prognostic relevance of cerbB2 expression following neoadjuvant chemotherapy in patients in a randomised trial of neoadjuvant versus adjuvant chemoendocrine therapy[J].Breast Cancer Res Treat,2000,59(2):171-175
[41]Steger GG,Wenzel C,Schmidinger M,et al.Predictive factors for a complete pathological response in primary breast cancer treated neoadjuvantly with epirubicin/PTXane+G-CSF regimen[J].Proc Am Soc Clin Oncol,2001,20:39a(abstract 154)
[42]Willsher PC,Pinder SE,Gee JM,et al.C-erbB-2 expression predicts response to preoperative chemotherapy for locally advanced breast cancer[J].Anticancer Res,1998,18(5B):3695-98
[43]Dagrada GP,Mezzelani A,Alasio L,et al.Her-2/neu assessment in primary chemotherapy treated breast carcinoma:no evidence of gene profile changing[J]. Breast Cancer Researeh &Treatment,2003,80(2):207-214
[44]M.Ruhul Quddus,C.James Sung,Cunxian Zhang,et al.HER-2/neu expression in locally advanced breast carcinomas:pre-and post-neoadjuvant chemotherapy [J]. Breast Cancer, 2005,12(4):294-298
[45]俞洋,杨红健,邹德宏.新辅助化疗后乳腺癌中CerbB-2的表达及意义[J].浙江临床医学杂志,2006,8(1)：3-4
[46]陈灿铭,沈镇宙.乳腺癌新辅助化疗疗效预测因子的研究现状[J].循证医学,2007,7(3)：132-134
[1]Inaji H,Komoike Y,Motomura K,et al.Breast-conserving treatment after neoadjuvant chemotherapy in large breast cancer[J].Breast Cancer,2002,9(1):20-25
[2]Bear HD,Anderson S,Brown A,et al.The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide:preliminary 'results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27[J]. J Clin Oncol,2003,21 (22):4165-4174
[3]van der Hage JA, van de Velde CJ, Julien JP, et al.Preoperative chemotherapy in primary operable breast cancer:results from the European Organization for Research and Treatment of Cancer trial 10902[J].Clin Oncol,2001,19(22):4224-4237
[4]Fisher B,Anderson S,Biyant J, et al.Twenty-year follow-up of a randomized trail comparing total mastectomy,lumpectomy,and lumpectomy plus irradiation for the treatment of invasive breast cancer[J].N Engl J Med,2002,347(16):1233-1241
[5]van der Hage J A, van de Velde CJ,Julien JP, et al. Preoperative chemotherapy inprimary operable breast cancer:results from the European Organization for Research and Treatment of Cancer trial 10902[J].Clin Oncol,2001,19:4224-4237
[6]Mamounas EP,Fisher B.Preoperative (neoadjuvant) chemotherapy in patients with breast cancer[J]. Semin Oncol,2001,28(4):389-399
[7]Fisher ER,Wang J,Bryant J,et al.Pathobiology of preoperative chemotherapy:findings from the National Surgical Adjuvant Breast and Bowel Project(NSABP) Protocol B-18[J]. Cancer,2002,95:681-695
[8]Bon adonna G,Valagussa P,Brambilla C,et al.Primary chemotherapy in operable breast cancer:eight-year experience at the Milan Cancer Institute[J].Clin Oncol,1998,16:93-100
[9]Sapunar F,Smith IE.Neoadjuvant chemotherapy for breast cancer[J].Ann med,2000,32: 43-50
[10]Howell A,Cuzick J,Baum M,et al.Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years'adjuvant treatment for breast cancer[J]. Lancet,2005,365(9453):60-62
[11]Jakesz R,Jonat M,Gnant M,et al.Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years'adjuvant tamoxifen:combined results of ABCSG trial 8 and ARNO 95 trial[J].Lancet,2005,366(9484):455-462
[12]Coombes RC,Hall E,Gibson LJ,et al.A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer[J].N Engl J Med,2004,350(11):1081-1092
[13]Goss PE,Ingle JN,Martino S,et al.A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early stage breast cancer[J].N Engl J Med,2003,349(19):1793-1802
[14]Cuzick J.Aromatase inhibitors for breast cancer prevention[J].J Clin Oncol,2005, 23(8):1636-1643
[15]Houssami N,Cuzick J,Dixon JM.The prevention,detection,and management of breast cancer[J]. Med J Aust,2006,184(5):230-234
[16]Romond EH,Perez E,Bryant J,et al.Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer[J].N Engl J Med,2005,353(16):1673-1684.
[17]左文述.现代乳腺肿瘤学[M].第2版,济南：山东科学技术出版社,2006.956
[18]Mamounas EP,Fisher B.Preoperative (neoadjuvant) chemotherapy in patients with breast cancer[J]. Semin Oncol,2001,28(4):389-399
[19]Van der Hage JA,van de Velde CJ,Julien JP,et al.Preoprative chemotherapy in primary operable breast cancer;results from the Europen Organization for Research and Treatment of Cancer trial 10902[J]J Clin Oncol,2001,19(22):4224-4237
[20]Estevez LG, Cuevas JM, Anton A,et al.Weekly docetaxel as neoadjuvant chemotherapy for stage Ⅱ and Ⅲ breast cancer:efficacy and correlation with biological markers in a phase Ⅱ,multicenter study[J].Clin Cancer Res,2003,9(2):686-692
[21]Kaufmann M, Hortobagyi GN, Goldhirsch A, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer:an update[J]. J Clin Oncol,2006,24(12):1940-1949
[22]Shimizu C,Ando M, Kouno T,et al.Current trends and controversies over pre-operative chemotherapy for women with operable breast cancer[J]Jpn J Clin Oncol,2007,37(1):1-8
[23]Isabelle VP,Herv C,Bernard L, etal. Efficacy of a primary chemotherapy regimen combining vinorelbine,epirubicin, and methotrexate(VEM)as neoadjuvant treatment in 89 patients with operable breast cancer [J]. The Oncologist,2002,7 (5):418-423
[24]陈灿铭,沈镇宙.乳腺癌新辅助化疗疗效预测因子的研究现状[J].循证医学,2007,7(3)：132-134
[25]Jensen EV,Block GE,Smith S,et al.Estrogen receptors and breast cancer response to adrenalectomy[J].Natl Cancer Inst Monogr,1971,34:55-70
[26]Althuis MD,Fergenbaum JH,Garcia-Closas M,et al.Etiology of hormone receptor-defined breast cancer:a systematic review of the literature[J].Cancer Epidemiol Biomarkers Prev,2004,13:1558-1568
[27]Jensen EV,Block GE,Ferguson DJ,et al.Estrogen receptors in breast cancer[J]. World J Surg,1977,1(3):341-342
[28]Bear HD,Anderson S, Smith RE,et al.Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27[J]. J Clin Oncol,2006, 24(13):2019-2027
[29]Ogston KN, Miller ID, Schofield AC, et al. Can patients'likelihood of benefiting from primary chemotherapy for breast cancer be predicted before commencement of treatment? [J].Breast Cancer Res Treat,2004,86(2):181-189
[30]Jain V, Landry M,Levine EA.The stability of estrogen and progesterone receptors in patients receiving preoperative chemotherapy for locally advanced breast carcinoma[J]. Am Surg,1996,62(2):162-165
[31]Piper GL,Patel NA,Patel JA,et al.Neoadjuvant chemotherapy for locally advanced breast cancer results in alterations in preoperative tumor marker status [J].Am Surg.2004,70(12): 1103-1106
[32]Taucher S,Rudas M,Gnant M,et al. Sequential steroid hormone receptor measurements in primary breast cancer with and without intervening primary chemotherapy[J].Endocr Relat Cancer,2003,10(1):91-98
[33]钟源,江学庆,尹美蓉,等.原癌基因C-erbB-2在乳腺癌中的表达及其临床意义[J].中国普通外科杂志,2008,17(5)：502-503
[34]Tamoxifen for early breast cancer:an overview of the randomized trials.Early Breast Cancer Trialists'Collaborative Group[J].Lancet 1998,351(9114):1451-1467
[35]Bardou VJ,Arpino G,Elledge RM,et al.Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases[J].J Clin Oncol 2003,21(10):1973-1979
[36]Willsher PC,Pinder SE,Gee JM,et al.C-erbB-2 expression predicts response to preoperative chemotherapy for locally advanced breast cancer[J].Anticancer Res,1998,18(5B): 3695-3698
[37]Eiermann W,Paepke S,Appfelstaedt J,et al.Preoperative treatment of postmenopausal breast cancer patients with letrozole.A randomized double-blind multicenter study[J].Ann Oncol 2001,12(11):1527-1532
[38]Lemmon MA,Schlessinger J.Regulation of signal transduction and signal diversity by receptor oligomerization[J].Trends Biochem Sci,1994,19(11):459-463
[39]Alroy I,Yarden Y.The ErbB signaling network in embryogenesis and oncogenesis:signal diversification through combinatorial ligand-receptor interactions[J].FEBS Letters,1997, 410(1):83-86
[40]Slamon DJ,Godolphin W,Jones LA,et al. Studies of the HER-2/neu proto-oncogene in human breast cancer [J].Science,1989,244(4905):707-712
[41]Press MF,Slamon DJ,Flom KJ,et al.Evaluation of HER-2/neu gene amplification and overexpression:comparison of frequently used assay methods in a molecularly characterized cohort of breast cancer specimens[J].J Clin Oncol,2002,20(14):3095-3105
[42]Robertson KW,Reeves JR,Smith G,et al.Quantitative estimation of epidermal growth factor receptor and C-erbB-2 in human breast cancer [J].Cancer Res,1996,56(16):3823-3830
[43]Yaziji H, Goldstein LC,Barry TS, et al.HER-2 testing in breast cancer using parallel tissue-based methods[J]. JAMA,2004,291 (16):1972-1977
[44]刘艳辉,张国淳.乳腺癌组织HER-2的荧光原位杂交和免疫组化联合检测的评价[J].循 证医学,2006,6(2)：81-83
[45]Yaziji H,Barry TS,Goldstein LC,et al.Discrepancies between immunohistochemistry and fluorescence in situ hybridization for HER-2 testing in breast cancer:The role of a quality assurance program on a cohort of 3564 patients:679[J] Journal of Clinical Oncology,2004, 22(14):465
[46]Thor AD,Berry DA,Budman DR, et al.erbB-2,p53,and efficacy of adjuvant therapy in lymph nodepositive breast cancer[J]J Natl Cancer Inst,1998,90(18):1346-1360
[47]Petit T,Borel C,Ghnassia JP,et al.Chemotherapy response of breast cancer depends on HER-2 status and anthracycline dose intensity in the neoadjuvant setting[J].Clin Cancer Res,2001,7(6):1577-1581
[48]Ciardiello F,Caputo R,Pomatico G,et al.Resistance to taxanes is induced by C-erbB-2 overexpression in human MCF-10A mammary epithelial cells and is blocked by combined treatment with an antisense oligonucleotide targeting type I protein kinase A[J].Int J Cancer,2000,85(5):710-715
[49]Ueno NT,Yu D,Hung MC.Chemosensitization of HER-2/neu-overexpressing human breast cancer cells to paclitaxel(Taxol) by adenovirus type 5 E1A[J]. Oncogene,1997,15(8):953-960
[50]Piccart-Gebhart MJ,Procter M,Leyland-Jones B,et al.Trastuzumab after adjuvant chemotherapy in HER-2-positive breast cancer[J].N Engl J Med,2005,353(16):1659-1672
[51]Slamon DJ,Leyland-Jones B,Shak S,et al.Use of chemotherapy plus a monoclonal antibody against HER-2 for metastatic breast cancer that overexpresses HER-2 [J].N Engl J Med,2001,344(11):783-792
[52]Cobleigh MA,Vogel CL,Tripathy D,et al.Multinational study of the efficacy and safety of humanized anti-HER-2 monoclonal antibody in women who have HER-2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease[J] J Clin Oncol,1999,17(9):2639-2648
[53]Vogel CL,Cobleigh MA,Tripathy D,et al.Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER-2-overexpressing metastatic breast cancer[J].J Clin Oncol,2002,20(3):719-726
[54]Ishihara Y,Harada M,Azuma K,et al.HER-2/neu-derived peptides recognized by both cellular and humoral immune systems in HLA-A2+cancer patients[J].Int J Oncol,2004, 24(4):967-975
[55]Slamon DJ,Clark GM,Wong SG,et al.Human breast cancer:correlation of relapse and survival with amplification of the HER-2/neu oneogene[J].Science,1987,235(4785): 177-182
[56]Tsutsui S,Ohno S,Murakami S,et al.Prognostic value of c-erbB-2 expression in breast cancer[J].J Surg Oncol,2002,79(4):216-223
[57]Fusun T,Semsi A,Cem U,et al. Association of HER-2/neu overexpression with the number of involved axillary lymph nodes in hormone receptor positive breast cancer patients[J].Exp Oncol,2005,27(2):145-149
[58]Ariga R,Zarif A,Korasick J,et al.Correlation of Her-2/neu gene amplification with other prognostic and predictive factors infemale breast carcinoma[J].Breast,2005,11(4):278-280
[2]Straver ME,Glas AM,Hannemann J,et al.The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer[J].Breast Cancer Res Treat,2010,119(3): 551-558
[3]Kumar A,Kumar R,Seenu V,et al.The role of 18F-FDG PET/CT in evaluation of early response to neoadjuvant chemotherapy in patients with locally advanced breast cancer[J].Eur Radiol,2009,19(6):1347-1357
[4]孙燕主编.肿瘤内科手册[M].第3版,北京：人民卫生出版社,1996.30-34
[5]左文述.现代乳腺肿瘤学[M].第2版,济南：山东科学技术出版社,2006.956
[6]Van der Hage JA,van de Velde CJ,Julien JP,et al.Preoprative chemotherapy in primary operable breast cancer;results from the Europen Organization for Research and Treatment of Cancer trial 10902[J].J Clin Oncol,2001,19(22):4224-4237
[7]Mamounas EP,Fisher B.Preoperative (neoadjuvant) chemotherapy in patients with breast cancer[J]. Semin Oncol,2001,28(4):389-399
[8]Nowell PC.The clonal evolution of tumor cell populations[J].Science,1976,194:23-28
[9]Drewinko B,Patehen M,Yang LY,et al.Differential killing efficacy of twenty antitumor drugs on proliferating and nonproliferating human tumor cells[J]. Cancer Res,1981, 41,2328-2333
[10]Grazia Arpino,Heidi Weiss,Adrian V,et al.Estrogen receptor-positive, progester-one receptor-negative breast cancer association with growth factor receptor expression and tamoxifen resistance[J].J National Cancer Institute,2005,97(17):1254-1261
[11]钟源,江学庆,尹美蓉,等.原癌基因C-erbB-2在乳腺癌中的表达及其临床意义[J].中国普通外科杂志,2008,17(5)：502-503
[12]王夫景,李刚,杨维良,等.乳癌p53与雌、孕激素受体的表达及临床意义[J].中国普通外科杂志,2002,6(11)：363-364
[13]于冰,丁锦辉,王闽全,等.乳腺浸润性导管癌中ER,PR,c-erbB-2, p53和nm23的表达及对预后的多因素分析[J].中国普通外科杂志,2007,16(11)：1118-1120
[14]Lehmann U,Glockner S,Kleeberger W,et al. Detection of gene amplification in archival breast cancer specimens by laserassisted microdissection and quantitative real-time polymerase chain reaction[J].Am J Pathol,2000,156:1855-1864
[15]张敏.乳癌含量测定及其预后关系[J].当代肿瘤病学,1994,1(1)：27-28
[16]McClelland RA,Gee JM,O'Sullivan L,et al.p21(WAF1) expression and endocrine response in breast cancer [J].J Pathol,1999,188(2):126-132
[17]沈镇宙,邵志敏.乳腺肿瘤学[M].上海：上海科学技术出版社,2005：147
[18]Bear HD,Anderson S, Smith RE,et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27[J]. J Clin Oncol,2006, 24(13):2019-2027
[19]Ogston KN, Miller ID, Schofield AC, et al. Can patients'likelihood of benefiting from primary chemotherapy for breast cancer be predicted before commencement of treatment? [J].Breast Cancer Res Treat,2004,86(2):181-189
[20]Fisher ER,Wang J,Bryant J,et al.Pathobiology of preoperative chemotherapy:findings from the National Surgical Adjuvant Breast and Bowel Project(NSABP) Protocol B-18[J]. Cancer,2002,95:681-695
[21]王丕琳,李玉文,尹子毅,等.表柔比星联合紫杉醇对浸润性导管癌新辅助化疗临床研究[J].中华肿瘤防治杂志,2007,14(9)：698-700
[22]刘伟平,臧家兰,蔡莉.乳腺癌生物学因子与新辅助化疗疗效的相关性分析[J].放射免疫学杂志,2009,22(1)：82-85
[23]Jain V, Landry M,Levine EA.The stability of estrogen and progesterone receptors in patients receiving preoperative chemotherapy for locally advanced breast carcinoma [J]. Am Surg,1996,62(2):162-165
[24]Lee SH, Chung MA,Quddus MR,et al.The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression and hormonal receptor status in breast cancer[J]. Am J Surg,2003,186(4):348-350
[25]Makris A, Powles TJ,Allred DC,et al.Quantitative changes in cytological molecular markers during primary medical treatment of breast cancer:a pilot study[J].Breast Cancer Res Treat,1999,53(1):51-59
[26]王殊,张嘉庆,乔心民,等.新辅助化疗对乳腺癌雌孕激素受体表达的影响[J].中华外科杂志,2005,15(43)：1011-1013
[27]Piper GL,Patel NA,Patel JA,et al.Neoadjuvant chemotherapy for locally advanced breast cancer results in alterations in preoperative tumor marker status[J].Am Surg.2004,70(12): 1103-1106
[28]Taucher S,Rudas M,Gnant M,et al.Sequential steroid hormone receptor measurements in primary breast cancer with and without intervening primary chemotherapy[J].Endocr Relat Cancer,2003,10(1):91-98
[29]Martin MB,Angeloni SV,Garcia-Morales P,et al.Regulation of estrogen receptor-alpha expression in MCF-7 cells by taxol[J].J Endocrinol,2004,180(3):487-496
[30]Fiegl H,Millinger S,Goebel G, et al.Breast cancer DNA methylation profiles in cancer cells and tumor stroma:association with HER-2/neu status in primary breast cancer [J].Cancer Res,2006,66(1):29-33
[31]Slamon DJ,Clark GM,Wong SG,et al.Human breast cancer:correlation of relapse and survival with amplification of the HER-2/neu oneogene[J].Science,1987,235(4785): 177-182
[32]Muss HB,Thor AD,Berry DA,et al.C-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer[J].N Engl J Med,1994, 330(18):1260-1266
[33]Tulbah AM, Ibrahim EM, Ezzat AA, et al. HER-2/neu overexpression does not predict response to neoadjuvant chemotherapy or prognosticate survival in patients with locally advanced breast cancer [J].Med Oncol,2002,19 (1):15-23
[34]Rozan S,Vincent-Salomon A,Zafrani B,et al.No significant predictive value of c-erbB-2 or p53 expression regarding sensitivity to primary chemotherapy or radiotherapy in breast cancer.[J].Int J Cancer,1998,79(1):27-33
[35]Zhang F,Yang Y,Smith T,et al.Correlation between Her-2 expression and response to neoadjuvant chemotherapy with 5-fluorouracil,doxorubicin,and cyclophosphamide in patients with breast carcinoma[J].Cancer,2003,97(7):1758-1765
[36]Niskanen E,Blomgvist C,Franssila K,et al.Predictive value of C-erbB-2,p53, cathepsin-D and histology of the primary tumour in metastatic breast cancer[J].Br J Cancer,1997, 76(7):917-922
[37]徐美玲,王继见.乳腺癌新辅助化疗疗效预测因子的初步研究.2007年P29
[38]Thor AD,Berry DA,Budman DR, et al.erbB-2,p53,and efficacy of adjuvant therapy in lymph nodepositive breast cancer[J].J Natl Cancer Inst,1998,90(18):1346-1360
[39]Pritchard K1,Shepherd LE,O'Malley FP,et al.HER-2 and responsiveness of breast cancer to adjuvant chemotherapy[J].N Engl J Med,2006,354(20):2103-2011
[40]Gregory RK, Powles TJ, Salter J,et,al.Prognostic relevance of cerbB2 expression following neoadjuvant chemotherapy in patients in a randomised trial of neoadjuvant versus adjuvant chemoendocrine therapy[J].Breast Cancer Res Treat,2000,59(2):171-175
[41]Steger GG,Wenzel C,Schmidinger M,et al.Predictive factors for a complete pathological response in primary breast cancer treated neoadjuvantly with epirubicin/PTXane+G-CSF regimen[J].Proc Am Soc Clin Oncol,2001,20:39a(abstract 154)
[42]Willsher PC,Pinder SE,Gee JM,et al.C-erbB-2 expression predicts response to preoperative chemotherapy for locally advanced breast cancer[J].Anticancer Res,1998,18(5B):3695-98
[43]Dagrada GP,Mezzelani A,Alasio L,et al.Her-2/neu assessment in primary chemotherapy treated breast carcinoma:no evidence of gene profile changing[J]. Breast Cancer Researeh &Treatment,2003,80(2):207-214
[44]M.Ruhul Quddus,C.James Sung,Cunxian Zhang,et al.HER-2/neu expression in locally advanced breast carcinomas:pre-and post-neoadjuvant chemotherapy [J]. Breast Cancer, 2005,12(4):294-298
[45]俞洋,杨红健,邹德宏.新辅助化疗后乳腺癌中CerbB-2的表达及意义[J].浙江临床医学杂志,2006,8(1)：3-4
[46]陈灿铭,沈镇宙.乳腺癌新辅助化疗疗效预测因子的研究现状[J].循证医学,2007,7(3)：132-134
[1]Inaji H,Komoike Y,Motomura K,et al.Breast-conserving treatment after neoadjuvant chemotherapy in large breast cancer[J].Breast Cancer,2002,9(1):20-25
[2]Bear HD,Anderson S,Brown A,et al.The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide:preliminary 'results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27[J]. J Clin Oncol,2003,21 (22):4165-4174
[3]van der Hage JA, van de Velde CJ, Julien JP, et al.Preoperative chemotherapy in primary operable breast cancer:results from the European Organization for Research and Treatment of Cancer trial 10902[J].Clin Oncol,2001,19(22):4224-4237
[4]Fisher B,Anderson S,Biyant J, et al.Twenty-year follow-up of a randomized trail comparing total mastectomy,lumpectomy,and lumpectomy plus irradiation for the treatment of invasive breast cancer[J].N Engl J Med,2002,347(16):1233-1241
[5]van der Hage J A, van de Velde CJ,Julien JP, et al. Preoperative chemotherapy inprimary operable breast cancer:results from the European Organization for Research and Treatment of Cancer trial 10902[J].Clin Oncol,2001,19:4224-4237
[6]Mamounas EP,Fisher B.Preoperative (neoadjuvant) chemotherapy in patients with breast cancer[J]. Semin Oncol,2001,28(4):389-399
[7]Fisher ER,Wang J,Bryant J,et al.Pathobiology of preoperative chemotherapy:findings from the National Surgical Adjuvant Breast and Bowel Project(NSABP) Protocol B-18[J]. Cancer,2002,95:681-695
[8]Bon adonna G,Valagussa P,Brambilla C,et al.Primary chemotherapy in operable breast cancer:eight-year experience at the Milan Cancer Institute[J].Clin Oncol,1998,16:93-100
[9]Sapunar F,Smith IE.Neoadjuvant chemotherapy for breast cancer[J].Ann med,2000,32: 43-50
[10]Howell A,Cuzick J,Baum M,et al.Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years'adjuvant treatment for breast cancer[J]. Lancet,2005,365(9453):60-62
[11]Jakesz R,Jonat M,Gnant M,et al.Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years'adjuvant tamoxifen:combined results of ABCSG trial 8 and ARNO 95 trial[J].Lancet,2005,366(9484):455-462
[12]Coombes RC,Hall E,Gibson LJ,et al.A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer[J].N Engl J Med,2004,350(11):1081-1092
[13]Goss PE,Ingle JN,Martino S,et al.A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early stage breast cancer[J].N Engl J Med,2003,349(19):1793-1802
[14]Cuzick J.Aromatase inhibitors for breast cancer prevention[J].J Clin Oncol,2005, 23(8):1636-1643
[15]Houssami N,Cuzick J,Dixon JM.The prevention,detection,and management of breast cancer[J]. Med J Aust,2006,184(5):230-234
[16]Romond EH,Perez E,Bryant J,et al.Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer[J].N Engl J Med,2005,353(16):1673-1684.
[17]左文述.现代乳腺肿瘤学[M].第2版,济南：山东科学技术出版社,2006.956
[18]Mamounas EP,Fisher B.Preoperative (neoadjuvant) chemotherapy in patients with breast cancer[J]. Semin Oncol,2001,28(4):389-399
[19]Van der Hage JA,van de Velde CJ,Julien JP,et al.Preoprative chemotherapy in primary operable breast cancer;results from the Europen Organization for Research and Treatment of Cancer trial 10902[J]J Clin Oncol,2001,19(22):4224-4237
[20]Estevez LG, Cuevas JM, Anton A,et al.Weekly docetaxel as neoadjuvant chemotherapy for stage Ⅱ and Ⅲ breast cancer:efficacy and correlation with biological markers in a phase Ⅱ,multicenter study[J].Clin Cancer Res,2003,9(2):686-692
[21]Kaufmann M, Hortobagyi GN, Goldhirsch A, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer:an update[J]. J Clin Oncol,2006,24(12):1940-1949
[22]Shimizu C,Ando M, Kouno T,et al.Current trends and controversies over pre-operative chemotherapy for women with operable breast cancer[J]Jpn J Clin Oncol,2007,37(1):1-8
[23]Isabelle VP,Herv C,Bernard L, etal. Efficacy of a primary chemotherapy regimen combining vinorelbine,epirubicin, and methotrexate(VEM)as neoadjuvant treatment in 89 patients with operable breast cancer [J]. The Oncologist,2002,7 (5):418-423
[24]陈灿铭,沈镇宙.乳腺癌新辅助化疗疗效预测因子的研究现状[J].循证医学,2007,7(3)：132-134
[25]Jensen EV,Block GE,Smith S,et al.Estrogen receptors and breast cancer response to adrenalectomy[J].Natl Cancer Inst Monogr,1971,34:55-70
[26]Althuis MD,Fergenbaum JH,Garcia-Closas M,et al.Etiology of hormone receptor-defined breast cancer:a systematic review of the literature[J].Cancer Epidemiol Biomarkers Prev,2004,13:1558-1568
[27]Jensen EV,Block GE,Ferguson DJ,et al.Estrogen receptors in breast cancer[J]. World J Surg,1977,1(3):341-342
[28]Bear HD,Anderson S, Smith RE,et al.Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27[J]. J Clin Oncol,2006, 24(13):2019-2027
[29]Ogston KN, Miller ID, Schofield AC, et al. Can patients'likelihood of benefiting from primary chemotherapy for breast cancer be predicted before commencement of treatment? [J].Breast Cancer Res Treat,2004,86(2):181-189
[30]Jain V, Landry M,Levine EA.The stability of estrogen and progesterone receptors in patients receiving preoperative chemotherapy for locally advanced breast carcinoma[J]. Am Surg,1996,62(2):162-165
[31]Piper GL,Patel NA,Patel JA,et al.Neoadjuvant chemotherapy for locally advanced breast cancer results in alterations in preoperative tumor marker status [J].Am Surg.2004,70(12): 1103-1106
[32]Taucher S,Rudas M,Gnant M,et al. Sequential steroid hormone receptor measurements in primary breast cancer with and without intervening primary chemotherapy[J].Endocr Relat Cancer,2003,10(1):91-98
[33]钟源,江学庆,尹美蓉,等.原癌基因C-erbB-2在乳腺癌中的表达及其临床意义[J].中国普通外科杂志,2008,17(5)：502-503
[34]Tamoxifen for early breast cancer:an overview of the randomized trials.Early Breast Cancer Trialists'Collaborative Group[J].Lancet 1998,351(9114):1451-1467
[35]Bardou VJ,Arpino G,Elledge RM,et al.Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases[J].J Clin Oncol 2003,21(10):1973-1979
[36]Willsher PC,Pinder SE,Gee JM,et al.C-erbB-2 expression predicts response to preoperative chemotherapy for locally advanced breast cancer[J].Anticancer Res,1998,18(5B): 3695-3698
[37]Eiermann W,Paepke S,Appfelstaedt J,et al.Preoperative treatment of postmenopausal breast cancer patients with letrozole.A randomized double-blind multicenter study[J].Ann Oncol 2001,12(11):1527-1532
[38]Lemmon MA,Schlessinger J.Regulation of signal transduction and signal diversity by receptor oligomerization[J].Trends Biochem Sci,1994,19(11):459-463
[39]Alroy I,Yarden Y.The ErbB signaling network in embryogenesis and oncogenesis:signal diversification through combinatorial ligand-receptor interactions[J].FEBS Letters,1997, 410(1):83-86
[40]Slamon DJ,Godolphin W,Jones LA,et al. Studies of the HER-2/neu proto-oncogene in human breast cancer [J].Science,1989,244(4905):707-712
[41]Press MF,Slamon DJ,Flom KJ,et al.Evaluation of HER-2/neu gene amplification and overexpression:comparison of frequently used assay methods in a molecularly characterized cohort of breast cancer specimens[J].J Clin Oncol,2002,20(14):3095-3105
[42]Robertson KW,Reeves JR,Smith G,et al.Quantitative estimation of epidermal growth factor receptor and C-erbB-2 in human breast cancer [J].Cancer Res,1996,56(16):3823-3830
[43]Yaziji H, Goldstein LC,Barry TS, et al.HER-2 testing in breast cancer using parallel tissue-based methods[J]. JAMA,2004,291 (16):1972-1977
[44]刘艳辉,张国淳.乳腺癌组织HER-2的荧光原位杂交和免疫组化联合检测的评价[J].循 证医学,2006,6(2)：81-83
[45]Yaziji H,Barry TS,Goldstein LC,et al.Discrepancies between immunohistochemistry and fluorescence in situ hybridization for HER-2 testing in breast cancer:The role of a quality assurance program on a cohort of 3564 patients:679[J] Journal of Clinical Oncology,2004, 22(14):465
[46]Thor AD,Berry DA,Budman DR, et al.erbB-2,p53,and efficacy of adjuvant therapy in lymph nodepositive breast cancer[J]J Natl Cancer Inst,1998,90(18):1346-1360
[47]Petit T,Borel C,Ghnassia JP,et al.Chemotherapy response of breast cancer depends on HER-2 status and anthracycline dose intensity in the neoadjuvant setting[J].Clin Cancer Res,2001,7(6):1577-1581
[48]Ciardiello F,Caputo R,Pomatico G,et al.Resistance to taxanes is induced by C-erbB-2 overexpression in human MCF-10A mammary epithelial cells and is blocked by combined treatment with an antisense oligonucleotide targeting type I protein kinase A[J].Int J Cancer,2000,85(5):710-715
[49]Ueno NT,Yu D,Hung MC.Chemosensitization of HER-2/neu-overexpressing human breast cancer cells to paclitaxel(Taxol) by adenovirus type 5 E1A[J]. Oncogene,1997,15(8):953-960
[50]Piccart-Gebhart MJ,Procter M,Leyland-Jones B,et al.Trastuzumab after adjuvant chemotherapy in HER-2-positive breast cancer[J].N Engl J Med,2005,353(16):1659-1672
[51]Slamon DJ,Leyland-Jones B,Shak S,et al.Use of chemotherapy plus a monoclonal antibody against HER-2 for metastatic breast cancer that overexpresses HER-2 [J].N Engl J Med,2001,344(11):783-792
[52]Cobleigh MA,Vogel CL,Tripathy D,et al.Multinational study of the efficacy and safety of humanized anti-HER-2 monoclonal antibody in women who have HER-2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease[J] J Clin Oncol,1999,17(9):2639-2648
[53]Vogel CL,Cobleigh MA,Tripathy D,et al.Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER-2-overexpressing metastatic breast cancer[J].J Clin Oncol,2002,20(3):719-726
[54]Ishihara Y,Harada M,Azuma K,et al.HER-2/neu-derived peptides recognized by both cellular and humoral immune systems in HLA-A2+cancer patients[J].Int J Oncol,2004, 24(4):967-975
[55]Slamon DJ,Clark GM,Wong SG,et al.Human breast cancer:correlation of relapse and survival with amplification of the HER-2/neu oneogene[J].Science,1987,235(4785): 177-182
[56]Tsutsui S,Ohno S,Murakami S,et al.Prognostic value of c-erbB-2 expression in breast cancer[J].J Surg Oncol,2002,79(4):216-223
[57]Fusun T,Semsi A,Cem U,et al. Association of HER-2/neu overexpression with the number of involved axillary lymph nodes in hormone receptor positive breast cancer patients[J].Exp Oncol,2005,27(2):145-149
[58]Ariga R,Zarif A,Korasick J,et al.Correlation of Her-2/neu gene amplification with other prognostic and predictive factors infemale breast carcinoma[J].Breast,2005,11(4):278-280