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1、VOLUME34?NUMBER6?FEBRUARY20,2016JOURNALOFCLINICALONCOLOGYEDITORIALLookingDeepIntotheHeterogeneityofHumanEpidermalGrowthFactorReceptor2–PositiveBreastCancer:CanWeUnderstandItBetter?ShereneLoiandPeterSavas,PeterMacCallumCancerCentre,EastMelbourne,Victoria,Au

2、straliaSeeaccompanyingarticleonpage542Thesuccessoftrastuzumabwhencombinedwithcytotoxicpoint,withallthebene?tsofrandomizedassignment,completeclinicalchemotherapytoalterthepreviouslyaggressivenaturalhistoryofannotation,andconsistenttreatmentadministration.Co

3、rrelativehumanepidermalgrowthfactorreceptor2(HER2)–positivediseasebiomarkerresultsfromaclinicaltrialaremorelikelytoberobust3hasbeenremarkable.Despiteintensiveresearch,understandingtheandreproducibleforthesereasons.2biologicfactorsthatleadtoresistanceinsome

4、patientsandtheInthestudybyCareyetal,thetrastuzumabandlapatinibintegrationofsuchfactorsintotheclinicalsettinghasbeenslow.combinationarmproducedanumericallyhigherbutnotstatisticallyTherelevanceofestrogenreceptor(ER)signalingintermsofre-signi?cantincreaseinth

5、eratesofpCRinthebreast,whichwasthesponseintheneoadjuvantsettingandprognosisintheadjuvantprimaryendpointofthestudy.Thetrastuzumab-alonecontrolarmwassettingisrecognizedbutdoesnotyetin?uencethewaywemanageobservedtohaveahigherpCRraterelativetothatinothercompar

6、able4,5anti-HER2therapy.Theidenti?cationofbothprognosticandpre-studies.Thismaybepartlyexplainedbytheinclusionofsmallerdictivefactorsbecomesparticularlycriticalasweseemtobemovingtumors($1cm).Notably,however,only64%ofpatientsintheintoaneraofdualanti-HER2ther

7、apy.TheCancerGenomeAtlaslapatinibarmand85%inthecombinationarm(evenafterlapatinibsubjected510primarybreasttumorstomutation,transcript,copydosereduction)comparedwith92%inthecontrolarmcompletednumber,methylation,andproteinanalyses.Only50%ofclinicaltheentirepr

8、otocol-speci?edneoadjuvanttherapy,whichmayhaveHER2-positivetumorswerecharacterizedasHER2enrichedatthecontributedtothelackofstatisticalsigni?canceforthecombinationmRNAandproteinlevel,andtherestwerepredominantl