局部晚期乳腺癌吡柔比星锁骨下动脉灌注与常规静脉化疗的疗效对比
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摘要
乳腺癌是女性最常见的恶性肿瘤之一，近年来我国乳腺癌发病率逐年上升，且发病年龄有年轻化趋势。由于医疗整体水平和人口素质的差别，在我国乳腺癌患者中，局部晚期乳腺癌患者占很大比例，此时由于肿块巨大，乳房皮肤受累面积广，腋窝淋巴结融合成团或腋血管受侵，常已无法一期行根治性切除，须行新辅助化疗。新辅助化疗可以使肿瘤明显缩小，降低肿瘤分期，并可改善区域淋巴结情况，使不可手术的局部晚期乳腺癌患者获得二期手术治疗的机会，且有助于早期杀灭亚临床转移灶，并可预测机体对化疗药物的敏感性。新辅助化疗有两种途径，一种是全身静脉化疗，另一种是经动脉灌注化疗。近年来随着介入放射学的发展和Seldinger技术的广泛应用，动脉灌注化疗已经变得十分简便、安全，目前Seldinger技术已成为动脉灌注化疗的标准方法，广泛应用于肝、肺、头颈、四肢等实体肿瘤的综合治疗之中。本文对吉林大学中日联谊医院乳腺外科2009年11月-2011年11月收治的58例Ⅲ期乳腺癌患者随机分为两组：经锁骨下动脉灌注组（动脉组）和全身静脉化疗组（静脉组），选择以吡柔比星为主的联合化疗方案，对比两组患者行新辅助化疗后的临床疗效及毒副作用，结果提示动脉组较静脉组具有更高的近期疗效和更低的全身毒副反应（p<0.05），从而证实动脉灌注化疗是一种更切实有效的晚期乳腺癌新辅助化疗方法。
Objective:To study the best way of neoadjuvant chemotherapy in locallyadvanced breast cancer.
Methods：Selecting58cases of breast cancer（stageⅢ） patients treatedin breast surgery，china-japan union hospital of jilin university，in November2009-November2011.All patients were randomly divided into two groups,including27cases of subclavian artery infusion groupe and31cases ofsystemic intravenous chemotherapy group.Both groupes took neoadjuvantchemotherapy mainly containing Pirarubicin.The chemotherapy drugs and thedoses were for cyclophosphamide500mg/m2, Pirarubicin40mg/m2，5-Fu500mg/m2.The artery group took subclavian artery perfusion chemotherapy bySeldinger’s technique following percutaneous femoral artery puncture, fourweeks as a course of treatment.The vein group was performanced by Peripheralintravenous drip only once，three weeks as a course of treatment, mean2to4course of treatment.After chemotherapy observing the clinical efficacy and theside reaction of two groups, doing a comparative study.
Results: The artery group was generally performanced preoperativechemotherapy for1to2courses of treatment，the vein group generally was for2to4courses of treatment.Though observation at two weeks afterchemotherapy，the tumor diameter of artery group reduced from7.08±1.34cmto3.83±1.22cm， while the tumor diameter of vein group reduced from7.15±1.41cm to5.19±1.19cm.The Clinical response rate in artery group was96.30%，while the vein group was41.94%.There was statistic difference between the two groups(P<0.05).Through observation before the operation，theClinical response rate in artery group was96.30%，while the vein group was90.32%，there was no statistic difference between the two groups(P>0.05). Thetime interval from Chemotherapy to operation in artery group was15.5士5.60days，while the vein group was60.10士16.34days，the former was obviouslyshorter than the latter. About the side effects of Chemotherapy，the bonemarrow inhibition and gastrointestinal reaction rate in artery group wassignificantly lower than the vein group，there was statistic difference betweenthe two groups(P<0.05).
Conclusion: Subclavian artery infusion with Pirarubicin is a practical andeffective method of neoadjuvant chemotherapy for locally advanced breastcancer, compared with systemic venous chemotherapy, it can improve thesuccess rate of operation and the resection rate in locally advanced breastcancer patients, reduce systemic adverse reaction，early remove the tumor,prevent metastasis and recurrence.
Objective:To study the best way of neoadjuvant chemotherapy in locallyadvanced breast cancer.
Methods：Selecting58cases of breast cancer（stageⅢ） patients treatedin breast surgery，china-japan union hospital of jilin university，in November2009-November2011.All patients were randomly divided into two groups,including27cases of subclavian artery infusion groupe and31cases ofsystemic intravenous chemotherapy group.Both groupes took neoadjuvantchemotherapy mainly containing Pirarubicin.The chemotherapy drugs and thedoses were for cyclophosphamide500mg/m2, Pirarubicin40mg/m2，5-Fu500mg/m2.The artery group took subclavian artery perfusion chemotherapy bySeldinger’s technique following percutaneous femoral artery puncture, fourweeks as a course of treatment.The vein group was performanced by Peripheralintravenous drip only once，three weeks as a course of treatment, mean2to4course of treatment.After chemotherapy observing the clinical efficacy and theside reaction of two groups, doing a comparative study.
Results: The artery group was generally performanced preoperativechemotherapy for1to2courses of treatment，the vein group generally was for2to4courses of treatment.Though observation at two weeks afterchemotherapy，the tumor diameter of artery group reduced from7.08±1.34cmto3.83±1.22cm， while the tumor diameter of vein group reduced from7.15±1.41cm to5.19±1.19cm.The Clinical response rate in artery group was96.30%，while the vein group was41.94%.There was statistic difference between the two groups(P<0.05).Through observation before the operation，theClinical response rate in artery group was96.30%，while the vein group was90.32%，there was no statistic difference between the two groups(P>0.05). Thetime interval from Chemotherapy to operation in artery group was15.5士5.60days，while the vein group was60.10士16.34days，the former was obviouslyshorter than the latter. About the side effects of Chemotherapy，the bonemarrow inhibition and gastrointestinal reaction rate in artery group wassignificantly lower than the vein group，there was statistic difference betweenthe two groups(P<0.05).
Conclusion: Subclavian artery infusion with Pirarubicin is a practical andeffective method of neoadjuvant chemotherapy for locally advanced breastcancer, compared with systemic venous chemotherapy, it can improve thesuccess rate of operation and the resection rate in locally advanced breastcancer patients, reduce systemic adverse reaction，early remove the tumor,prevent metastasis and recurrence.
引文
[1]孙燕.内科肿瘤学[M].北京：人民卫生出版社，2001：4l9-420.
[2] Tokura H，Ikeda T，Kitajima M，et al.Intra-arterial infusion chemotherapyfor breast cancer[J].Gan to Kayaku Ryoho，2002，29（2）：176-181.
[3]郭小毛，梅欣，辛倩.局部晚期乳腺癌的治疗进展[J].中国癌症杂志，2006，16（6）：409-416．
[4] Ena G.Neoadjuvant therapy in breast cancer[J].Rev Med Brux，2011，32（4）：243-246.
[5] Untch M，von Minckwitz G.Neoadjuvant chemotherapy：early response asa guide for further treatment：clinical，radiological，and biological[J].J NatlCancer Inst Monogr，2011，2011（43）：138-141.
[6] Moreno-Aspitia， Alvaro.Neoadjuvant therapy in early-stage breastcancer[J].Critical reviews in oncology/hematology，2012，82（2）：187-199.
[7] Stephens FO.Intra-arterial induction chemotherapy in locally advancedstage Ⅲ breast cancer[J].Cancer，1990，66（4）：645-650.
[8] Li XR，Wang JD，Zhang YJ，et al.Effects of neoadjuvant chemotherapy ofdocetaxel combined with and epirubicin or pirarubicin on breast cancer：clinical analysis of160cases[J]. Zhonghua Yi Xue Za Zhi，2009，89（2）：87-90.
[9]郭仁宣主编.乳腺癌外科学[M].沈阳：辽宁科学技术出版社，2003，8-9.
[10]Bilbao JI， Reboll J， Longo JM， et al.Neoadjuvant Intra-arterialchemotherapy in inflammatory carcinoma of the breast cancer[J]. Brit JRadiol，1992，65（2）：248-251.
[11]周汝明，邱水波，刘闽华，等.乳腺癌的血液供应及术前动脉灌注化疗[J].中国医学影像技术，2008，24：1449-1452．
[12]Vanel D.Interventional radiology： the new daily work of the breastradiologist[J].Eur J Radiol，2002，42（1）：1-4．
[13]何劲松，朱国献，郭良峰，等.立体超选择性动脉灌注化疗在乳腺癌降期保乳术中的价值[J].中国普外基础与临床杂志，2008，15（12）：929-930.
[14]甘长清，苏新良，杨光伦，等.经尺动脉介入化疗治疗局部晚期乳腺癌27例报告[J].重庆医学，2005，34（3）：407-408.
[15]何建苗，崔科英，吴有军，等.术前动脉灌注化疗联合热疗对晚期乳腺癌细胞凋亡及相关基因表达的影响[J].解放军医学杂志，2011，36（10）：1095-1097.
[16]Fiorentini G， Tsetis D， Varveris C， et al.Induction Intra-arterialChemotherapy (IAC) with Epirubicin and Mitoxantrone in LocallyAdvanced Breast Cancer[J].Induction Chemotherapy，2011，139-149.
[17]Shimamoto H，Takizawa K，Ogawa Y，et al.Clinical efficacy and value ofredistributed subclavian arterial infusion chemotherapy for locallyadvanced breast cancer[J]. Jpn J Radiol，2011，29：236-243.
[18]Pacetti P, Mambrini A，Paolucci R，et al.Intra-arterial Chemotherapy：ASafe Treatment for Elderly Patients with Locally Advanced BreastCancer[J]. In Vivo，2006，20:761-764.
[19]Yamada T，Yuyama Y，Okazaki Y.A long-surviving patient with Stage IVbreast cancer with no recurrence after combined therapy of medroxyprogesterone acetate (MPA) and intra-arterial infusionchemotherapy[J].Gan to kagaku ryoho. Cancer&chemotherapy，2004，31（9）：1387-1389.
[20]Takatsuka Y，Yayoi E，Kabayashi T，et al.Neoadjuvant intra-arterialchemotherapy in locally advanced breast cancer：a prospective randomizedstudy[J].Jpn J Clin Oncol，1994，24：20-25.
[1]孙燕.内科肿瘤学[M].北京：人民卫生出版社，2001：419-420.
[2] Ena G.Neoadjuvant therapy in breast cancer[J].Rev Med Brux，2011，32（4）：243-246.
[3] Untch M，von Minckwitz G.Neoadjuvant chemotherapy：early response asa guide for further treatment：clinical，radiological，and biological[J].J NatlCancer Inst Monogr，2011，2011（43）：138-141.
[4] Moreno-Aspitia， Alvaro.Neoadjuvant therapy in early-stage breastcancer[J].Critical reviews in oncology/hematology，2012，82（2）：187-199.
[5] Klopp GT，Alford TC，Bateman J，et al.Fractionated intra-arterial cancerchemotherapy[J].Ann surg，1950，132：811-832.
[6] Byron RL，Yonemoto RH，Hallauer WC，et al.Radical mastectomy witharterial regional chemotherapy[J].Surgery，1961，49：681-686.
[7] Koyama H， Nishizawa Y， Wada T， et al.Intra-arterial infusionchemotherapy as an induction therapy in multidisciplinary treatment forlocally advanced breast cancer[J].Cancer，1985，56：725-727.
[8] Hortobagyi GN，Ames FC，Buzdar AU，et al.Management of stageⅢprimary breast cancer with primary chemotherapy，surgery，and radiationtherapy[J].Cancer，1988，62：2507-2516.
[9]何劲松，朱国献，郭良峰，等.立体超选择性动脉灌注化疗在乳腺癌降期保乳术中的价值[J].中华普外基础与临床杂志，2008，15（12）：929-930.
[10]李少林，任国胜，陈晓品，等.乳腺癌的基础理论和临床实践[M].北京：科学出版社，2008，609.
[11]Tokura H，Ikeda T，Kitajima M，et al.Intra-arterial infusion chemotherapyfor breast cancer[J].Gan to Kayaku Ryoho，2002，29（2）：176-181.
[12]Shi P，Wang MM，Jiang LY，et al.Paclitaxel–doxorubicin sequence is moreeffective in breast cancer cells with heat shock protein27overexpression[J].Chin Med J (Engl)，2008，121：1975-1979.
[13]郭仁宣主编.乳腺癌外科学[M].沈阳：辽宁科学技术出版社，2003，8-9.
[14]Bilbao JI，Reboll J，Longo Jl，et al.Neoadjuvant Intra-arterial chemotherapyin inflammatory carcinoma of the breast cancer[J]. Brit J Radiol，1992，65（2）：248-251.
[15]Vanel D.Interventional radiology： the new daily work of the breastradiologist[J].Eur J Radiol，2002，42（1）：1-4．
[16]刘光元，曹建民，陈自谦.肿瘤血管介人治疗[M].南京：江苏科学技术出版社，2003：94-97.
[17]甘长清，苏新良，杨光伦，等.经尺动脉介入化疗治疗局部晚期乳腺癌27例报告[J].重庆医学，2005，34（3）：407-408.
[18]甘长清，苏新良，杨光伦.经股动脉介入化疗中晚期乳腺癌近期疗效观察[J].重庆医科大学学报，2005，30（2）：310-317.
[19]黄昌明，张祥福，卢辉山，等. Ⅲ期乳腺癌术前尺动脉插管灌注化疗的远期疗效[J].中华外科杂志，2000，38（6）：412-414.
[20]Fiorentini G， Tsetis D， Varveris C， et al.Induction Intra-arterialChemotherapy (IAC) with Epirubicin and Mitoxantrone in LocallyAdvanced Breast Cancer[J].Induction Chemotherapy，2011，139-149.
[21]Shimamoto H，Takizawa K，Ogawa Y，et al.Clinical efficacy and value ofredistributed subclavian arterial infusion chemotherapy for locallyadvanced breast cancer[J]. Jpn J Radiol，2011，29：236-243.
[22]Pacetti P, Mambrini A，Paolucci R，et al.Intra-arterial Chemotherapy：ASafe Treatment for Elderly Patients with Locally Advanced BreastCancer[J]. In Vivo，2006，20:761-764.
[23]Yamada T，Yuyama Y，Okazaki Y.A long-surviving patient with Stage IVbreast cancer with no recurrence after combined therapy of medroxyprogesterone acetate (MPA) and intra-arterial infusion chemotherapy[J].Gan to kagaku ryoho. Cancer&chemotherapy，2004，31（9）：1387-1389.
[24]Maes T，Wildiers H，Heye S，et al.Intra-hepatic Mitomycin C bolusinfusion in the treatment of extensive liver metastases of breast cancer[J].Breast Cancer Res Treat，2008，110：135-142.
[25]TakatsukaY，Yayoi E，Kabayashi T，et al.Neoadjuvant intra-arterialchemotherapy in locally advanced breast cancer：a prospective randomizedstudy[J].Jpn J Clin Oncol，1994，24：20-25.
[26]黄昌明，张祥福，卢辉山，等.Ⅲ期乳腺癌术前尺动脉插管灌注化疗和全身静脉化疗的疗效对比[J].福建医科大学学报，2006，40（2）：154-157.
[27]何建苗，崔科英，吴有军，等.术前动脉灌注化疗联合热疗对晚期乳腺癌细胞凋亡及相关基因表达的影响[J].解放军医学杂志，2011，36（10）：1095-1097.
[28]中华医学会.临床技术操作规范[M].北京：人民军医出版社，2006：55-57.
[29]Stephens FO.Intra-arterial induction chemotherapy in locally advancedstage Ⅲ breast cancer[J].Cancer，1990，66（4）：645-650.
[2] Tokura H，Ikeda T，Kitajima M，et al.Intra-arterial infusion chemotherapyfor breast cancer[J].Gan to Kayaku Ryoho，2002，29（2）：176-181.
[3]郭小毛，梅欣，辛倩.局部晚期乳腺癌的治疗进展[J].中国癌症杂志，2006，16（6）：409-416．
[4] Ena G.Neoadjuvant therapy in breast cancer[J].Rev Med Brux，2011，32（4）：243-246.
[5] Untch M，von Minckwitz G.Neoadjuvant chemotherapy：early response asa guide for further treatment：clinical，radiological，and biological[J].J NatlCancer Inst Monogr，2011，2011（43）：138-141.
[6] Moreno-Aspitia， Alvaro.Neoadjuvant therapy in early-stage breastcancer[J].Critical reviews in oncology/hematology，2012，82（2）：187-199.
[7] Stephens FO.Intra-arterial induction chemotherapy in locally advancedstage Ⅲ breast cancer[J].Cancer，1990，66（4）：645-650.
[8] Li XR，Wang JD，Zhang YJ，et al.Effects of neoadjuvant chemotherapy ofdocetaxel combined with and epirubicin or pirarubicin on breast cancer：clinical analysis of160cases[J]. Zhonghua Yi Xue Za Zhi，2009，89（2）：87-90.
[9]郭仁宣主编.乳腺癌外科学[M].沈阳：辽宁科学技术出版社，2003，8-9.
[10]Bilbao JI， Reboll J， Longo JM， et al.Neoadjuvant Intra-arterialchemotherapy in inflammatory carcinoma of the breast cancer[J]. Brit JRadiol，1992，65（2）：248-251.
[11]周汝明，邱水波，刘闽华，等.乳腺癌的血液供应及术前动脉灌注化疗[J].中国医学影像技术，2008，24：1449-1452．
[12]Vanel D.Interventional radiology： the new daily work of the breastradiologist[J].Eur J Radiol，2002，42（1）：1-4．
[13]何劲松，朱国献，郭良峰，等.立体超选择性动脉灌注化疗在乳腺癌降期保乳术中的价值[J].中国普外基础与临床杂志，2008，15（12）：929-930.
[14]甘长清，苏新良，杨光伦，等.经尺动脉介入化疗治疗局部晚期乳腺癌27例报告[J].重庆医学，2005，34（3）：407-408.
[15]何建苗，崔科英，吴有军，等.术前动脉灌注化疗联合热疗对晚期乳腺癌细胞凋亡及相关基因表达的影响[J].解放军医学杂志，2011，36（10）：1095-1097.
[16]Fiorentini G， Tsetis D， Varveris C， et al.Induction Intra-arterialChemotherapy (IAC) with Epirubicin and Mitoxantrone in LocallyAdvanced Breast Cancer[J].Induction Chemotherapy，2011，139-149.
[17]Shimamoto H，Takizawa K，Ogawa Y，et al.Clinical efficacy and value ofredistributed subclavian arterial infusion chemotherapy for locallyadvanced breast cancer[J]. Jpn J Radiol，2011，29：236-243.
[18]Pacetti P, Mambrini A，Paolucci R，et al.Intra-arterial Chemotherapy：ASafe Treatment for Elderly Patients with Locally Advanced BreastCancer[J]. In Vivo，2006，20:761-764.
[19]Yamada T，Yuyama Y，Okazaki Y.A long-surviving patient with Stage IVbreast cancer with no recurrence after combined therapy of medroxyprogesterone acetate (MPA) and intra-arterial infusionchemotherapy[J].Gan to kagaku ryoho. Cancer&chemotherapy，2004，31（9）：1387-1389.
[20]Takatsuka Y，Yayoi E，Kabayashi T，et al.Neoadjuvant intra-arterialchemotherapy in locally advanced breast cancer：a prospective randomizedstudy[J].Jpn J Clin Oncol，1994，24：20-25.
[1]孙燕.内科肿瘤学[M].北京：人民卫生出版社，2001：419-420.
[2] Ena G.Neoadjuvant therapy in breast cancer[J].Rev Med Brux，2011，32（4）：243-246.
[3] Untch M，von Minckwitz G.Neoadjuvant chemotherapy：early response asa guide for further treatment：clinical，radiological，and biological[J].J NatlCancer Inst Monogr，2011，2011（43）：138-141.
[4] Moreno-Aspitia， Alvaro.Neoadjuvant therapy in early-stage breastcancer[J].Critical reviews in oncology/hematology，2012，82（2）：187-199.
[5] Klopp GT，Alford TC，Bateman J，et al.Fractionated intra-arterial cancerchemotherapy[J].Ann surg，1950，132：811-832.
[6] Byron RL，Yonemoto RH，Hallauer WC，et al.Radical mastectomy witharterial regional chemotherapy[J].Surgery，1961，49：681-686.
[7] Koyama H， Nishizawa Y， Wada T， et al.Intra-arterial infusionchemotherapy as an induction therapy in multidisciplinary treatment forlocally advanced breast cancer[J].Cancer，1985，56：725-727.
[8] Hortobagyi GN，Ames FC，Buzdar AU，et al.Management of stageⅢprimary breast cancer with primary chemotherapy，surgery，and radiationtherapy[J].Cancer，1988，62：2507-2516.
[9]何劲松，朱国献，郭良峰，等.立体超选择性动脉灌注化疗在乳腺癌降期保乳术中的价值[J].中华普外基础与临床杂志，2008，15（12）：929-930.
[10]李少林，任国胜，陈晓品，等.乳腺癌的基础理论和临床实践[M].北京：科学出版社，2008，609.
[11]Tokura H，Ikeda T，Kitajima M，et al.Intra-arterial infusion chemotherapyfor breast cancer[J].Gan to Kayaku Ryoho，2002，29（2）：176-181.
[12]Shi P，Wang MM，Jiang LY，et al.Paclitaxel–doxorubicin sequence is moreeffective in breast cancer cells with heat shock protein27overexpression[J].Chin Med J (Engl)，2008，121：1975-1979.
[13]郭仁宣主编.乳腺癌外科学[M].沈阳：辽宁科学技术出版社，2003，8-9.
[14]Bilbao JI，Reboll J，Longo Jl，et al.Neoadjuvant Intra-arterial chemotherapyin inflammatory carcinoma of the breast cancer[J]. Brit J Radiol，1992，65（2）：248-251.
[15]Vanel D.Interventional radiology： the new daily work of the breastradiologist[J].Eur J Radiol，2002，42（1）：1-4．
[16]刘光元，曹建民，陈自谦.肿瘤血管介人治疗[M].南京：江苏科学技术出版社，2003：94-97.
[17]甘长清，苏新良，杨光伦，等.经尺动脉介入化疗治疗局部晚期乳腺癌27例报告[J].重庆医学，2005，34（3）：407-408.
[18]甘长清，苏新良，杨光伦.经股动脉介入化疗中晚期乳腺癌近期疗效观察[J].重庆医科大学学报，2005，30（2）：310-317.
[19]黄昌明，张祥福，卢辉山，等. Ⅲ期乳腺癌术前尺动脉插管灌注化疗的远期疗效[J].中华外科杂志，2000，38（6）：412-414.
[20]Fiorentini G， Tsetis D， Varveris C， et al.Induction Intra-arterialChemotherapy (IAC) with Epirubicin and Mitoxantrone in LocallyAdvanced Breast Cancer[J].Induction Chemotherapy，2011，139-149.
[21]Shimamoto H，Takizawa K，Ogawa Y，et al.Clinical efficacy and value ofredistributed subclavian arterial infusion chemotherapy for locallyadvanced breast cancer[J]. Jpn J Radiol，2011，29：236-243.
[22]Pacetti P, Mambrini A，Paolucci R，et al.Intra-arterial Chemotherapy：ASafe Treatment for Elderly Patients with Locally Advanced BreastCancer[J]. In Vivo，2006，20:761-764.
[23]Yamada T，Yuyama Y，Okazaki Y.A long-surviving patient with Stage IVbreast cancer with no recurrence after combined therapy of medroxyprogesterone acetate (MPA) and intra-arterial infusion chemotherapy[J].Gan to kagaku ryoho. Cancer&chemotherapy，2004，31（9）：1387-1389.
[24]Maes T，Wildiers H，Heye S，et al.Intra-hepatic Mitomycin C bolusinfusion in the treatment of extensive liver metastases of breast cancer[J].Breast Cancer Res Treat，2008，110：135-142.
[25]TakatsukaY，Yayoi E，Kabayashi T，et al.Neoadjuvant intra-arterialchemotherapy in locally advanced breast cancer：a prospective randomizedstudy[J].Jpn J Clin Oncol，1994，24：20-25.
[26]黄昌明，张祥福，卢辉山，等.Ⅲ期乳腺癌术前尺动脉插管灌注化疗和全身静脉化疗的疗效对比[J].福建医科大学学报，2006，40（2）：154-157.
[27]何建苗，崔科英，吴有军，等.术前动脉灌注化疗联合热疗对晚期乳腺癌细胞凋亡及相关基因表达的影响[J].解放军医学杂志，2011，36（10）：1095-1097.
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