交接2015年6月案子ztcf反饋件predicting the axillary lymph node metastasis early-stage breast cancer using subtype

TripleNegativeBreastCancerwasAssociatedwithaReducedRiskofAxillaryLymphaticSpreadObjective:Theclinicalvalueofbreastcancersubtype(BCS)asapproximatedbyestrogenreceptor(ER),progesteronereceptor(PR),andhumanepidermalgrowthfactorreceptor2(HER2)inpredictingthestatusofaxillarylymphnodeinearly-stagebreastcancerisstillcontroversial.ThepurposeofthisstudywastodeterminewheatherBCScouldpredicttheaxillarylymphnodemetastasisinearly-stagebreastcancer.Method:Patientsreceivedbreastconservingsurgeryormastectomy,andaxillarylymphnodedissectionwereidentifiedfromtwocancercenterexcludingthosewhoreceivedneoadjuvantchemotherapy.Theassociationsbetweenclinicopathologicvariablesandaxillarylymphnodeinvolvementatthetimeofdiagnosiswereevaluatedinunivariateandmultivariateregression yses,includingthesignificanceofBCSResults:Ofthe3,471patientsincludedinthisstudy,53.0%hadaxillarylymphnodemetastasesatdiagnosis.Patientswithhormonereceptor(HR)-/HER2-subtypemorefrequentlyhighgradeandhighestrateofLVI,butlowerproportionwithpositivelymphnodesthanotherBCS.TheunivariateandmultivariablelogisticregressionysisshowedthatBCSwasstatisticallysignificantpredictoroflymphnodepositivity.PatientswiththeHR-/HER2-subtypehadthelowestoddsofhavingpositiveaxillarylymphnodethanotherBCS.HR+/HER2-,HR+/HER2+,andHR-/HER2+tumorswere1.651times(95%confidenceinterval[CI]1.349-2.021),1.958times(95%CI2.486),and1.525times(95%CI1.181-1.970)morelikelywithnodalmetastasesthanHR-/HER2-subtype.Univariateandmultivariablelogisticregressionysisalsoshowedthatlargertumorsize,highgradeandlymphovascularinvasionwereassociatedwithanincreasedriskofnodalmetastases.ConclusionsTheBCSasapproximatedbyER,PR,andHER2aresignificantlyassociatedwithaxillarylymphnodemetastasisinearly-stagebreastcanceratthetimeofdiagnosis.HR-/HER2-wasassociatedwithareducedriskofaxillaryspreadcomparedtopatientswithother:Breastcancer,Breastcancersubtype,Axillarylymphnode,Triplenegativebreastcancer,Lymphovascularinvasion腋窩淋狀態(tài)是制 術(shù)后綜合治療方案及分期的重要依據(jù)同時是判斷患者的預(yù)后因一（1。長期以來，腋窩淋清掃術(shù)一直是乳腋窩淋狀態(tài)評估的重要然而該將造成上肢水腫等嚴(yán)重并發(fā)癥。、哨淋已經(jīng)作為早期腋窩淋狀態(tài)的重要評估(2,3)，但仍缺乏確切的辦法來預(yù)測患者的腋窩淋狀態(tài)。之前的研究已經(jīng)發(fā)現(xiàn)腫瘤部、近年有研究發(fā)現(xiàn)基于estrogenreceptor(ER),progesteronereceptor(PR),and亦是腋窩淋轉(zhuǎn)移的因一但是其價值仍存在爭（9-13特別是三陰乳（14（910過回顧分析兩個腫瘤中心的患者的臨床病理資料，探討不同BCS的腋窩淋狀態(tài)的情況。

Patientsand回顧性分析廈門大學(xué)附屬第一醫(yī)院（廈門市腫瘤中心，XiamenCancerCenter，XMCC）SunYat-senUniversityCancerCenter（SYSUCC）收治的乳患者，按以下標(biāo)準(zhǔn)進行入組：1；2；34wasapprovedbytheethicscommitteeoftheFirstAffiliatedHospitalofXiamenUniversityandSYSUCC.Allpatientsprovidedwrittenconsentforstorageoftheirmedicalinformationinthehospitaldatabaseandforresearchuseofthisinformation.hormonereceptor（HR）ERPR1%HER-2陽性定義為免疫組化3+2+FISHBCS的定義為：HR+/HER2-(ER+and/orPR+,HER2+),HR+/HER2+(ER+and/orPR+,TNBC)。Nodalpositivitywasdefinedasthepresenceofanytumorcellsinalymphnodeandincludedmacrometastases,micrometastases,andisolatedtumorcells.患者的分期按照第七版的聯(lián)合(AmericanJointCommitteeonCancer,AJCC)/國際抗癌(UnionforInternationalCancerControl,UICC)分期指預(yù)測腋窩淋狀態(tài)的因、采用臨床病理因素來預(yù)測腋窩淋狀態(tài)主要包括狀態(tài)tumorsize、grade、LVI，ER、PR、HER2BCS等。、StatisticalAlldatawereyzedusingtheSPSSstatisticalsoftwarepackage(version16.0;IBMCorporation,Armonk,NY,USA).Theχ2testandFisher’sexactprobabilitytestswereusedforcategoricalvariablesandysisofvarianceforcontinuousvariablestocomparethedistributionofclinicopathologiccharacteristicsamongBCS.Therelationshipbetweenpatients'characteristicsandaxillarylymphnodemetastaseswasexaminedbyunivariateandmultivariablelogisticregressionysis.Thepredictfactorsonaxillarylymphnodemetastasesweredeterminedbymultivariablelogisticregressionysis,inwhichfactorsthatwerestatisticallysignificantinunivariateysiswereenteredintomultivariablelogisticregressionysis.AP-value<0.05wasconsideredsignificantinallyses.XMCC2809PatientandtumorcharacteristicsareshowninTable1.53.0%患者腋窩淋陽性。57.8%ER陽性，63.4%PR陽性，33.1%HER2陽性。ThedistributionofBCSinthestudypopulationwas50.7%HR+/HER2-,19.2%HR+/HER2+,13.9%HR-/HER2+,and16.2%HR-/HER2-.PatientandtumorcharacteristicsdividedbysubtypearedisyedinTable2.AmongtheBCS,thereweresignificantdifferencesinage(P=0.021),menopausalstatus(P<0.001),pTstages(P<0.001),pNstages(P<0.001),grades(P<0.001),andLVI(P=0.005).Patientswith/HER2-subtypemorefrequentlyhighergradeandhighestrateofLVI,butlowerproportionwithpositivelymphnodesthanotherBCS.Table3presentstheresultsoftheunivariatendlogisticregressionysis.Largertumorsize,highergrade,LVI,ERpositive,PRpositive,andHER2positivewerecorrelatedwithhighriskoflymphnodalmetastases.OnunivariateysisusedBCS,BCSwasstatisticallysignificantpredictoroflymphnodepositivity.HR+/HER2-,HR+/HER2+,andHR-/HER2-subtypeshadstatisticallyhigherprobabilitywithpositivelymphnodes,HR-/HER-subtypearenotmorelikelytohaveinvolvedlymphTheresultsofthemultivariableysisareshowninTable4.Inmodel1,whenadjustedfortumorsize,grade,LVI,ER,PR,andHER2,increasingtumorsize,highergrade,LVI,PRpositive,andHER2positivewerepredictorsofaxillarylymphnodespositivity.ERwasnotastatisticallysignificantpredictorofpositivelymphnode.WheninModel2adjustedfortumorsize,grade,LVI,andBCS,thetumorsize,gradeandLVIremainedpredictorsofnodalmetastases.Specifically,patientswiththeHR-/HER2-subtypehadthelowestoddsofhavingpositiveaxillarylymphnodethanotherBCS.HR+/HER2-,HR+/HER2+,andHR-/HER2+tumorswere1.651times(95%CI1.349-2.021),1.958times(95%CI1.542-2.486),and1.525times(95%CI1.181-1.970)likelywithnodalmetastasesthanHR-/HER2-subtype.HR-/HER2+subtypehadareducedriskofaxillarylymphnodeinvolvementcomparedtotheHR+/HER2+subtype,withanoddsratio(OR)of0.779(95%CI0.609-0.997,P=0.0048)inthemultivariateER、PRHER2BCS對腋窩淋狀態(tài)的預(yù)測，結(jié)果提示TNBC的患者的淋轉(zhuǎn)移率顯著低于其他BCS。腋窩淋狀態(tài)仍是評估患者的預(yù)后指導(dǎo)輔助治療的選擇的重要因素?；谖鞣降娜巳貉芯恐邪l(fā)現(xiàn)、腫瘤部位、tumorstage、grade和LVI等可以作為預(yù)測腋窩淋狀態(tài)的（4-8。但在我們的基于群的研究中亦發(fā)現(xiàn)tumorstage、grade和LVI亦為影響患者腋窩淋狀態(tài)的因素而則無預(yù)測價值同樣在一個韓國人群的研究中取得相似的結(jié)果(11)。研究也發(fā)現(xiàn)olderwomenweremorelikelytohavepositivelymphnodeswithincreasingage(15).也許東西方的發(fā)病在方面存在差異（16，因此，作為腋窩淋的預(yù)測因素可能受到因素的影響（17。轉(zhuǎn)移率顯著低于其他BCS。共入組20009例患者的DanishBreastCancerCooperativeGroupdatabaseTNBCpatientshaveareducedriskofALNinvolvementatthetimeofdiagnosiscomparedtopatientswithothersubtypes,whensubtypes（10NationalCancerCenter的研究分析了3198例患者亦發(fā)現(xiàn)TNBC的淋陽性概44.8%（18測患者的腋窩淋狀態(tài)仍有爭議。有研究發(fā)現(xiàn)TNBC患者的淋陽性概率2.09（11（12TNBCtumorsdidnothaveinvolvedlymphnodesmoreoftenthanTNBC（13LVIisanobligatorystepintumorprogressiontowardmetastasizingand,therefore,maybeasurrogatemarkerformetastaticpotential(21).TNBC患（14,2213.4%亦發(fā)現(xiàn)其他三個BCS的LVI度（OR1.7-2.5）顯著高于TNBC亞型的患者(10)。結(jié)合我們的研究及相關(guān)研究結(jié)果，TNBC的陽性淋轉(zhuǎn)移概率更低，其（23,24前提。Inpatientswithpositivesentinellymphnode，theriskofpositivenonsentinelnodesinTNBCLuminalALumianlBHER2過表達(dá)型患者差異不明顯(25)。dman等的研究中，TNBChadthelowestriskofnon-sentinelLymphNodemetastasisinbreastcancerpatientswithpositivesentinellymphnodesthanothersubtypes（26）.這提示BCS可能可作為指導(dǎo)腋窩淋清掃的重要因素的三陰的患者可能可以避免腋窩淋清掃但ACOSOG（2,3，3471例。Second，由于入組的時間跨度較長，ThebreastcancersubtypeswerenotdeterminedaccordingtothecriteriadevelopedintheSt.GallenInternationalBreastCancerConferencebecause6（27ER、PR及HER2，而不是基于型的BCS，可能會存在一定的誤差(28)。TheBCSasapproximatedbyER,PR,andHER2aresignificantlyassociatedwithaxillarylymphnodemetastasisinearly-stagebreastcanceratthetimeofdiagnosis.TNBC亞型患者的腋窩淋巴BCSHR-/HER2-的患者LayeequrRahmanR,CrawfordSL,SiwawaP.Managementofaxillainbreastcancer-Thesagacontinues.Breast.2015Apr27.pii:S0960-9776(15)00078-8.:GiulianoAE,McCallL,BeitschP,WhitworthPW,BlumencranzP,LeitchAM,SahaS,HuntKK,MorrowM,BallmanK.Locoregionalrecurrenceaftersentinellymphnodedissectionwithorwithoutaxillarydissectioninpatientswithsentinellymphnodemetastases:theAmericanCollegeofSurgeonsOncologyGroupZ0011randomizedtrial.AnnSurg.2010;252(3):426-32;discussion432-3.GiulianoAE,HuntKK,BallmanKV,BeitschPD,WhitworthPW,BlumencranzPW,LeitchAM,SahaS,McCallLM,MorrowM.Axillarydissectionvsnoaxillarydissectioninwomenwithinvasivebreastcancerandsentinelnodemetastasis:arandomizedclinicaltrial.JAMA.2011;305(6):569-75.BevilacquaJL,KattanMW,FeyJV,CodyHS3rd,BorgenPI,VanZeeKJ.Doctor,whataremychancesofhavingapositivesentinelnode?Avalidatednomogramforriskestimation.JClinOncol.2007Aug20;25(24):3670-9.YoshiharaE,SmeetsA,LaenenA,ReyndersA,SoensJ,VanOngevalC,MoermanP,ParidaensR,WildiersH,NevenP,ChristiaensMR.Predictorsofaxillarylymphnodemetastasesinearlybreastcancerandtheirapplicabilityinclinicalpractice.Breast.VialeG,ZurridaS,MaioranoE,MazzarolG,PruneriG,PaganelliG,MaisonneuveP,VeronesiU.Predictingthestatusofaxillarysentinellymphnodesin4351patientswithinvasivebreastcarcinomatreatedinasingleinstitution.Cancer.2005;103(3):492-GreerLT,RosmanM,CharlesMylanderW,LiangW,BurasRR,ChagparAB,EdwardsMJ,TafraL.Apredictionmodelforthepresenceofaxillarylymphnodeinvolvementinwomenwithinvasivebreastcancer:afocusonolderwomen.BreastJ.CrabbSJ,CheangMC,LeungS,ImmonenT,NielsenTO,HuntsmanDD,BajdikCD,ChiaSK.Basalbreastcancermolecularsubtypepredictsforlowerincidenceofaxillarylymphnodemetastasesinprimarybreastcancer.ClinBreastCancer.Holm-RasmussenEV,JensenMB,BalslevE,KromanN,TvedskovTF.Reducedriskofaxillarylymphaticspreadintriple-negativebreastcancer.BreastCancerResTreat.2015;149(1):229-36.UgrasS,StempelM,PatilS,MorrowM.Estrogenreceptor,progesteronereceptor,andHER2statuspredictlymphovascularinvasionandlymphnodeinvolvement.AnnSurgOncol.2014;21(12):3780-6.LeeJH,KimSH,SuhYJ,ShimBY,KimHK.Predictorsofaxillarylymphnodemetastases(ALNM)inaKoreanpopulationwithT1-2breastcarcinoma:triplenegativebreastcancerhasahighincidenceofALNMirrespectiveofthetumorsize.CancerResTreat.2010;42(1):30-6.GangiA,MirochaJ,LeongT,GiulianoAE.Triple-negativebreastcancerisnotassociatedwithincreasedlikelihoodofnodalmetastases.AnnSurgOncol.WieannL,SampsonM,StempelM,JacksLM,PatilSM,KingT,MorrowM.Presentingfeaturesofbreastcancerdifferbymolecularsubtype.AnnSurgOncol.FoulkesWD,SmithIE,Reis-FilhoJS.Triple-negativebreastcancer.NEnglJMed.WildiersH,VanCalsterB,vandePoll-FranseLV,HendrickxW,R?islienJ,SmeetsA,ParidaensR,DeraedtK,LeunenK,WeltensC,VanHuffelS,ChristiaensMR,NevenP.Relationshipbetweenageandaxillarylymphnodeinvolvementinwomenwithbreastcancer.JClinOncol.2009;27(18):2931-7.FanL,Strasser-WeipplK,LiJJ,StLouisJ,FinkelsteinDM,YuKD,ChenWQ,ShaoZM,GossPE.Breastcancerin.LancetOncol.2014;15(7):e279-89.MamounasEP.Ageandlymphnodestatusinbreastcancer:notastraightforwardrelationship.JClinOncol.2009;27(18):2900-1.ZhuX,YingJ,WangF,WangJ,YangH.Estrogenreceptor,progesteronereceptor,andhumanepidermalgrowthfactorreceptor2statusininvasivebreastcancer:a3,198casesstudyatNationalCancerCenter,.BreastCancerResTreat.SchoppmannSF,BayerG,AumayrK,TaucherS,GeleffS,RudasM,KubistaE,HausmaningerH,SamoniggH,GnantM,JakeszR,HorvatR;AustrianBreastandColorectalCancerStudyGroup.Prognosticvalueoflymphangiogenesisandlymphovascularinvasionininvasivebreastcancer.AnnSurg.2004;240(2):306-12.MooTA,McMillanR,LeeM,StempelM,HoA,PatilS,El-TamerM.ImpactofmolecularsubtypeonlocoregionalrecurrenceinmastectomypatientswithT1-T2breastcancerand1-3positivelymphnodes.AnnSurgOncol.2014;21(5):1569-74.Nofech-MozesS,AckermanI,GhorabZ,IsmiilN,ThomasG,CovensA,KhalifaMA.Lymphovascularinvasionisasignificantpredictorfordistantrecurrenceinpatientswithearly-stageendometrialendometrioidadenocarcinoma.AmJClinPathol.DentR,TrudeauM,PritchardKI,HannaWM,KahnHK,SawkaCA,LickleyLA,RawlinsonE,SunP,NarodSA.Triple-negativebreastcancer:clinicalfeaturesandpatternsofrecurrence.ClinCancerRes.2007;13(15Pt1):4429-34.SackeyH,MagnusonA,SandelinK,LiljegrenG,BergkvistL,FülepZ,CelebiogluF,FrisellJ.Armlymphoedemaafteraxillarysurgeryinwomenwithinvasivebreastcancer.BrJSurg.2014;101(4):390-7.DeGournayE,GuyomardA,CoutantC,BouletS,ArveuxP,CauseretS,GouyS,PadeanoMM,LoustalotC,SauzeddeJM,SmailM,CombierJP,ChevilloteP,RosburgerC,BonnetainF,FraisseJ,Dabakuyo-YonliTS.Impactofsentinelnodebiopsyonlong-termqualityoflifeinbreastcancerpatients.BrJCancer.ZhouW,HeZ,XueJ,WangM,ZhaX,LingL,ChenL,WangS,LiuX.Molecularsubtypeclassificationisadeterminantofnon-sentinellymphnodemetastasisinbreastcancerpatientswithpositivesentinellymphnodes.PLoSOne.2012;7(4):e35881.dmanGM,FowbleBL,LiT,HwangES,SchechterN,DevarajanK,AndersonPR,SigurdsonER,GoldsteinLJ,BleicherRJ.Riskofpositivenonsentinelnodesinwomenwith1-2positivesentinelnodesrelatedtoageandmolecularsubtypeapproximatedbyreceptorstatus.BreastJ.2014;20(4):358-63.GoldhirschA,WinerEP,CoatesAS,GelberRD,Piccart-GebhartM,ThürlimannB,SennHJ;Panelmembers.alizingthetreatmentofwomenwithearlybreastcancer:highlightsoftheStGallenInternationalExpertConsensusonthePrimaryTherapyofEarlyBreastCancer2013.AnnOncol.2013;24(9):2206-23.NguyenPL,TaghianAG,KatzMS,NiemierkoA,AbiRaadRF,BoonWL,BellonJR,WongJS,SmithBL,HarrisJR.Breastcancersubtypeapproximatedbyestrogenreceptor,progesteronereceptor,andHER-2isassociatedwithlocalanddistantrecurrenceafterbreast-conservingtherapy.JClinOncol.2008;26(14):2373-8.Table1 Clinicopathologicalcharacteristicsofpatientswithbreastcancerintwocancercenter.Age≤73364437>35-33914911830>2509541204Menopausal437184122782259681193Tumor194944113838915941983611812421890108Nodal26913611630167804971106357463120287407I1783695472581248150622611921418408270931172541003544311892231917Breastcancer330143315651066674407481 102 459 561XMCC,XiamenCancer