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HER2

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HER2

    HER2

JournalofZhejiangUniversitySCIENCEB

    ;ISSN1673-1581(Print);ISSN1862-1783(Online) ;wwwzjueducn0zus;wwwspdngerlink.corn

    ;E-mail:jZUS@zjueducn

    ;Zhangetat/dZhejiangUnivSciB2008e(I)-5-9 ;HER2over-?expressionandresponsetodifferent ;chemotherapyre-

    ;mensinbreastcancer

    ;JinZHANG.YanLIU

    ;(DepartmentofBreastCance~CancerInstituteandHospital,Tianj’inMedica

    lUniversity,Tianjin300060,China)

    ;E-mail:davidz9132002@yahoo.com

    ;ReceivedDec.3,2007;revisionacceptedDec.10,2007 ;5

    ;Abstract:Purpose:ToexamtherelationshipbetweenHER2overexpressio

    nanddifferentadjuvantchemotherapiesinbreast ;cancer.PatientsandMethods:Atotalofl625primarybreastcancerpatientswh

    oreceivedpost.surgeryadjuvantchemotherapyin ;TianjinCancerHospital,China,fromJuly2002toNovember2005wereinclu

dedinthestudy.Amongthem.600patientswere

    ;givenCMF(CTX+MTX+5

    Fu)regimen,600givenCEF(CTX+EADM+5.Fu)regimen,and425givenan

    thracyclinesplus

    ;taxanesregimen,withmeanfollow-uptimeof42months.Results:InCMFtreatmentgroup,the3-yeardiseasefreesurvival(DFS)

    ;inHER2overexpressedpatientswaslowerthanthatoftheHER2

    negativeones(89.80%vs91.24%.P=0.0348);innodepositive

    expressedpatients,an;subgroup,the3-yearDFSwas84.72%inHER2over

    d90.18%intheHER2negativeones(P=0.027l1.

    ;ComparedtoCMFregimen,anthracyclinesandanthracyclinesplustaxanesregimensaremoreeffectivefJD<0.05)innodepositive

    ;HER2overexpressionthanthoseinthenodenegative.Conclusion:HER

    2overexpressionisanindependentindexforpredicting

    ;poorprognosisandshortDFSforbreastcancerpatients.HER2overexpress

    edpatientsareresistanttoCMFregimenchemo

    ;therapy,butsensitivetoanthracyclines.basedoranthracyclinesplustaxanesregimen.HER2expressioncanbetakenasamarker

    ;fortherapiesinbreastcancer.

    ;Keywords:Breastcancer,HER2,Chemotherapy

    ;doi:10.1631/jzus.B073003Documentcode:ACLCnumber:R737;R730.54 ;rNTR0DUCT10N

    ;Breastcancerthreatenswomenalloverthe ;world,andhasbecomethesecondcauseforfemale ;deaths.InChina.theincidenceofbreastcancerhas ;beenincreasingandhasbecomethemostcommon ;femalemalignanttumor(ShenandShao,2002). ;HER2/neuisamemberoftheerbBlikeoncogene

    ;family,andisrelatedto,butdistinctfrom,theepi

    ;dermalgrowthfactorreceptor.

    ;Thisoncogenehasbeenshowntobeamplifiedin ;humanbreastcancercelllines.Manystudiesshowa ;closecorrelationbetweentheexpressionOfHER2/ ;neuandprognosisinbreastcancer(Ferrettieta1.. ;2007;R6villioneta1..2007).HER2hasbecomethe ;independentprognosticfactorfortumorrelapseand ;totalsurvivaltime.BeingHER2positiveindicatesa ;poorprognosis,i.e.,shorteroverallsurvivaltime, ;pooreroutcomeinnode-negativepatientswhencom-

    ;binedwithSt.Gallenclassification.pooreroutcomein ;nodepositivepatients,earlierrelapseafteradjuvant ;chemotherapyandsoon(Pritchardeta1.,2006). ;Inthisstudy,weanalysed1625primarybreast ;cancerpatientswhoreceivedadjuvantchemotherapy

    ;afteroperationduringJuly2002toNovember2005, ;reportingthecorrelationbetweenHER2overex

    ;pressionandtheresponsetodifferentadjuvantther

    ;apyinbreastcancer.

    ;PATIENTSANDMETH0DS

    ;Studypopulation

    ;Atotalof1625primarybreastcancerpatients ;whoreceivedadjuvantchemotherapyafteroperation ;wereincludedinthestudy.Amongthem.600patients ;agedfrom27to89years,withmeanageof50years, ;weregivenCMFregimen(C:600mg/mIVonDayI, ;

    ;6Zhangetal/JZhejiangUnivSciB20089f”5—9

    ;M:40mg/m’IVonDay1.F:500mg/m’IVonDay1.

    ;q3w~6),and56caseshadrelapseandmetastasisand ;l0died.Another600caseswithagerangeof23to75 ;yearsandmeanage0f49yearsweregivenCEF ;regimen(C:600mg/m’IVonDayl,E:75-90mg/m

    ;IVonDayl,F:500mg/m’IVonDayl,q3wx6),and

    ;40casesrelapsedandmetastasizedand2died.The ;remaining425cases,agedfrom22-89yearswith ;meanage0f49years.weregivenanthracyclinesplus

;taxanesregimen(TEorTEC6circles.orECP8

    ;circles;T:75mg/m’IVonDay1.E:60mg/mIVon

    ;DayI,q3wx6;P:I75mg/mIVonDayl,q3wx4), ;and3lrelapsedordevelopedmetastasisand3died. ;Meanfollowuptimewas42months.

    ;Materialsandstatisticalanalysis

    ;AllofthecaseswereconfirmedbyIHCSP

    ;method.HER2waspreviouslytestedforprotein ;overexpressionbyHercepTest(groupedintoHercep ;0,1+,2+and3+).

    ;Diseasefreesurvival(DFS)rateofpatientswas ;describedbyDFScurvebyKaplanMeiermethod,

    ;andlog..rankwasappliedtoobservewhetherstatis.. ;ticaldifferenceofDFSexistedbetweenHER2posi

    ;tiveandHER2negativesubgroups.Thestatistical ;analysiswascarriedoutusingSPSS12.0statistical ;analysissoftware.

    ;RESULTS

    ;ResponsetoCMFregimeninHER2over?expressed ;patients

    ;InCMFtreatmentgroup.HER2overexpressed

    ;patientshada3yearDFS0f89.80%.whereasthe

;3yearDFSwas9l-24%inHER2negativepatients

    ;(P=-0.0348,Fig.1).ItprobablysuggeststhatHER2 ;over..expressedpatientswereresistanttoCMFregi.- ;mentherapy.Innodenegativesubgroup(377cases), ;the3yearDFSinHER2overexpressedpatientswas

    ;91.40%.whereas92.70%inHER2negativeones

    ;(P=-0.935l1.Innodepositivesubgroup(223cases), ;the3yearDFSinHER2overexpressedpatientswas

    ;84.72%.but90.18%inHER2negativeones(P=

    ;0.0271.Fig-21.TheseresultsindicatethatHER2 ;overexpressedpatientswereresistanttoCMFregi

    ;men.andthenodenegativeHER2overexpression

    ;patientswerenotresistanttoCMFregimenbutonly ;node?-positiveHER2over?-expressedpatientswere ;resistanttoCMFregimen.

    ;11O

    ;100

    ;90

    ;

    ;Q

    ;80

    ;70

;0102O3O4050

    ;Monthsonstudy

    ;Fig.1Diseasefreesurvival(DFS)curvediagramin ;HER2over-expressedorHER2-negativepatientsgiven ;CMF

    ;100

    ;9O

    ;

    ;

    ;Q8O

    ;70

    ;01020304050

    ;Monthsonstudy

    ;Fig.2Diseasefreesurvival(DFS)curvediagramin ;node-positivepatients

    ;ResponsetoCEFregimeninHER20Veexpressed

    ;patients

    ;InCEFtherapygroup.the3yearDFSinHER2

    ;overexpressedpatientswas90.10%.and9l-23%in ;HER2negativepatientsfP=-0.30l01.Innodenegative

    ;subgroup(290cases).the3yearDFSinHER2

    ;overexpressedpatientswas92.71%.and93.84%in

;HER2negativeonesfP=0.78351.Innodepositive

    ;subgroupf3l0cases),the3yearDFSinHER2

    expressedpatientswas90.10%.and9l-23%in ;over

    ;HER2negativeonesfP=0.2555).Theresultsshow ;thattherewasnodifferenceof3yearDFSbetween

    ;HER2overexpressedandHER2negativepatients

    ;withCEFregimen.ThismayindicatethatHER2 ;overexpressedpatientsweresusceptlvetoanthracy

    basedregimen. ;clines

    ;

    ;Zhangetal/JZhejiangUnivSciB20089(1)5?9 ;Responsetoanthracyclinesplustaxanesregimen ;inHER2over.expressedpatients

    ;Inanthracyclinesplustaxanestherapygroup,the ;3.yearDFSinHER2over-expressedpatientswas ;91.04%.and92.03%inHER2.negativeones ;(P=0.0715).Innode-negativesubgroup(104cases), ;the3.yearDFSinHER2over.expressedpatientswas ;91.72%.and92.26%inHER2.negativeones ;(P=0.4326).Innode-positivesubgroup(32lcases), ;the3.yearDFSinHER2overexpressedpatientswas

    ;89.85%.and90.24%inHER2.negativeones

    ;(P=0.96141.Theseresultssuggestnodifierenceof ;3.yearDFSbetweenHER2overexpressedand

    ;HER2-negativepatientsgivenanthracyclinesplus ;taxanesregimen.ItindicatesthatHER2

    ;over-expressedpatientsweresusceptivetoanthracy

    ;clinesplustaxanesregimen.

    ;Comparisonofresponsetodifferentchemother

    ;apyregimensinHER20Ver-expressedpatients ;InHER2overexpressedpatientsf425cases.

    ;featureslistedinTable11.the3.yearDFSinCMF ;therapywas89.4l%.inCEFtreatmentwas92.67%. ;andinanthracyclinesplustaxanesregimenwas ;91.53%.The3.yearDFSinCMFregimenwaslower ;thanthatofanthracyclinesandanthracyclinesplus ;taxanesregimens(P=0.045,Fig.3),suggestingthat ;anthracyclinesbasedandanthracvclinesplustaxanes ;regimensweremoreeffectivethanCMFforHER2 ;over-expressedpatients.Nodifierencebetweenan

    ;thracyclines.basedandanthracyclinesplustaxanes ;regimensforHER2over..expressedpatientswasob.. ;served(P=0.786).

    ;1OO

;95

    ;90

    ;Q

    ;85

    ;80

    ;O102O3O4050

    ;Monthsonstudy

    ;Fig.3Diseasefreesurvival(DFS)curveinHER2 ;over-expressedpatientstreatedbydifferentchemo- ;therapyregimens

    ;T-based:Anthracyclinesplustaxanesregimen ;7

    ;Innode..positiveHER2over..expressedsubgroup ;(235cases,patientsfeatureslistedinTable2),the ;3yearDFSinCMFtreatmentwas84.70%.inC:EF ;treatmentwas90.76%.andinanthracyclinesplus ;taxanestreatmentwas89.74%.ComparedtoCMF ;regimen,anthracyclinesandtaxanesweremoreef- ;fective(P=-0.03l,Fig.4).Nodifferencebetweenan. ;thracyclines.basedandanthracyclinesplustaxanes ;regimensforHER2over.expressedpatients(P=0.843) ;wasobserved.Theseresultssuggestthatanthracy.

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