不同分子亚型Ⅰ、Ⅱ期乳腺癌新辅助化疗的趋势

不同分子亚型Ⅰ、Ⅱ期乳腺癌新辅助化疗的趋势摘要：乳腺癌是女性最常见的恶性肿瘤之一，分子分型的不同对于治疗和预后有着重要意义。本文旨在探讨乳腺癌不同分子亚型Ⅰ、Ⅱ期患者新辅助化疗的趋势。目前，HER2过表达、三阴性和激素受体阳性的乳腺癌是治疗难点，因此针对不同亚型的治疗策略是不同的。HER2过表达乳腺癌患者可以采用三重负荷的药物治疗，包括赫赛汀（trastuzumab）、多西他赛（docetaxel）和氟尿嘧啶（5-FU）。对于激素受体阳性乳腺癌患者，内分泌治疗的有效性更高，新辅助内分泌治疗的意义在于优化患者手术方式和治疗安排。三阴性乳腺癌的治疗往往包括铂类药物、多西他赛、毒蕈碱类药物等多种方案的组合使用。本文综述了乳腺癌不同分子亚型Ⅰ、Ⅱ期患者新辅助化疗的最新进展及应用前景。

关键词：乳腺癌；分子分型；新辅助化疗；HER2过表达；激素受体阳性；三阴性

Introduction

Breastcancerisoneofthemostcommonmalignanttumorsinwomen,andthemolecularsubtypeshaveimportantsignificancefortreatmentandprognosis.ThepurposeofthispaperistoexplorethetrendofneoadjuvantchemotherapyfordifferentmolecularsubtypesofbreastcancerinstagesIandII.Currently,HER2-overexpressing,triple-negative,andhormonereceptor-positivebreastcanceraredifficulttotreat,sothetreatmentstrategiesfordifferentsubtypesaredifferent.HER2-overexpressingbreastcancerpatientscanbetreatedwithtripletdrugs,includingtrastuzumab,docetaxel,andfluorouracil.Forhormonereceptor-positivebreastcancerpatients,theeffectivenessofendocrinetherapyishigher,andthesignificanceofneoadjuvantendocrinetherapyistooptimizepatients'surgicalproceduresandtreatmentarrangements.Thetreatmentoftriple-negativebreastcanceroftenincludesacombinationofplatinumdrugs,docetaxel,amatoxin,andotherschemes.ThispaperreviewsthelatestprogressandapplicationprospectsofneoadjuvantchemotherapyfordifferentmolecularsubtypesofbreastcancerinstagesIandII.

HER2-overexpressingBreastCancer

HER2overexpressionisthemainfeatureofHER2-overexpressingbreastcancer,accountingforabout20%ofcases.TrastuzumabisaHER2monoclonalantibody,blockingtheHER2receptor,andinhibitingtheproliferationandmigrationofbreastcancercells.Docetaxelisamicrotubuleinhibitorthatcanpreventspindleformationandpreventcelldivision.FluorouracilisapyrimidineanaloguethatcaninterferewithDNAandRNAsynthesis.Thecombinationofthesethreedrugscanachieveasynergisticeffect,enhancetheefficacyofchemotherapy,andimprovethepathologicalcompleteresponserate(pCR)ofpatientswithHER2-overexpressingbreastcancer(Slamonetal.,2011).

HormoneReceptor-positiveBreastCancer

Hormonereceptor-positivebreastcanceraccountsforabout70%ofallbreastcancercases.Endocrinetherapyhasbecomethemainmethodoftreatinghormonereceptor-positivebreastcancer.Neoadjuvantendocrinetherapycanreducetumorsizeandimproveoperability,especiallyforhormonereceptor-positiveelderlypatientswhodonotmeetthesurgicalstandards.Thebenefitsofneoadjuvantendocrinetherapyincludedown-stagingthetumor,improvingsurgicalprocedures,andavoidingunnecessarymutilation(Thomasetal.,2018).Therearetwomaintypesofendocrinetherapy:selectiveestrogenreceptormodulators(SERMs)andaromataseinhibitors(s).TamoxifenisthemostcommonlyusedSERM,whichcanblocktheestrogenreceptorandinhibitthegrowthandproliferationofbreastcancercells.scaninhibitthesynthesisofestrogen,thusachievingthegoaloftreatinghormonereceptor-positivebreastcancer.

Triple-negativeBreastCancer

Triple-negativebreastcanceraccountsforabout15%ofallbreastcancercases.Thistypeofcancerlackstheexpressionofestrogen,progesterone,andHER2receptors,andisresistanttotraditionalendocrinetherapyandtargetedtherapy.Platinumdrugshavesignificantefficacyinthetreatmentoftriple-negativebreastcancer.ThemechanismofactionistoformacomplexwithDNA,interferewithDNAreplication,andkillcancercells.Neoadjuvantchemotherapyfortriple-negativebreastcanceroftenincludesacombinationofplatinumdrugsandtaxanedrugs.Studieshaveshownthatthepathologicalcompleteresponserateofneoadjuvantchemotherapyfortriple-negativebreastcancerishigherthanthatofothersubtypes,andpatientscanobtainthemaximumtherapeuticbenefits(Silveretal.,2010).

Conclusion

Neoadjuvantchemotherapyisanimportantpartofbreastcancertreatment.Fordifferentmolecularsubtypesofbreastcancer,newneoadjuvantchemotherapystrategieshavebeendeveloped,whichcaneffectivelyimprovethepCRrateandlong-termsurvivalrateofpatients.HER2-overexpressingbreastcancercanbetreatedwithtripletdrugstoachieveasynergisticeffect.Hormonereceptor-positivebreastcancercanbenefitfromneoadjuvantendocrinetherapy,whichcanreducetumorsizeandimproveoperabilitywhileavoidingunnecessarymutilation.Triple-negativebreastcancerisresistanttotraditionalendocrinetherapyandtargetedtherapy,andplatinumdrugshavesignificantefficacy.Inthefuture,withthedevelopmentoftargetedtherapy,neoadjuvantchemotherapyforbreastcancerwillhavemoreprecise,personalizedandeffectivetreatmentstrategies.

Keywords:breastcancer;molecularsubtype;neoadjuvantchemotherapy;HER2-overexpressing;hormonereceptor-positive;triple-negativeBreastcancerisacomplexdiseaseandisclassifiedintodifferentmolecularsubtypesbasedonthepresenceorabsenceofhormonereceptors(HR),humanepidermalgrowthfactorreceptor2(HER2),andothergeneticmarkers.Thethreemajorsubtypesarehormonereceptor-positive(HR+),HER2-overexpressing,andtriple-negativebreastcancer(TNBC).Eachmolecularsubtypehasdifferenttreatmentoptionsandprognosis.

Neoadjuvantchemotherapyisatypeoftherapythatisgivenbeforesurgerytoreducethesizeofthetumorandincreasethelikelihoodofsuccessfulsurgicalremoval.Thistreatmentstrategyhasbecomethestandardofcareforlocallyadvancedbreastcancerandisincreasinglybeingusedforearlierstagedisease.Neoadjuvantchemotherapyhasseveraladvantages,includingtheabilitytoevaluatetheresponsetotreatment,assessthetumor'sbiology,andpotentiallyeliminatemicrometastases.

Theselectionofneoadjuvantchemotherapyisbasedonthepatient'smolecularsubtype.ForHR+breastcancer,hormonetherapyisusuallythefirst-linetreatment,butincaseswherethetumorislargeorlocallyadvanced,neoadjuvantchemotherapymaybeused.HER2+breastcanceristreatedwithtargetedtherapyinadditiontochemotherapy,withtrastuzumabbeingthepreferredagent.ForTNBC,neoadjuvantchemotherapyisthemainstayoftreatmentsincethissubtypedoesnotrespondtohormonetherapyortargetedtherapy.

Platinumdrugs,suchascisplatinandcarboplatin,haveshownsignificantefficacyinthetreatmentofTNBC.ThesedrugsworkbydamagingtheDNAofcancercells,leadingtotheirdeath.However,notallTNBCpatientsrespondtoplatinumdrugs,andthereisaneedforbiomarkerstoidentifythosewhoarelikelytobenefit.

Inconclusion,neoadjuvantchemotherapyisanimportanttreatmentstrategyforbreastcancer.Withthedevelopmentoftargetedtherapy,neoadjuvantchemotherapyisexpectedtobecomemorepersonalizedandeffectiveinthefuture.ItisimportanttotailorthetreatmentapproachtothemolecularsubtypeofbreastcancerwhileavoidingunnecessarymutilationInadditiontoneoadjuvantchemotherapy,thereareseveralothertreatmentoptionsforbreastcancer,includingsurgery,radiationtherapy,andadjuvantsystemictherapy.Surgeryisusuallythefirst-linetreatmentforlocalizedbreastcancerandinvolvestheremovalofthetumorandsurroundingtissue.Radiationtherapyisoftenusedaftersurgerytokillanyremainingcancercellsandreducetheriskofrecurrence.Adjuvantsystemictherapy,whichincludeshormonetherapyandtargetedtherapy,isusedtokillanyremainingcancercellsthatmayhavespreadbeyondthebreast.

Hormonetherapyisusedforhormonereceptor-positivebreastcancer,whichaccountsforapproximatelytwo-thirdsofallbreastcancers.Hormonetherapyworksbyblockingtheeffectsofestrogenandcanbegivenbeforeoraftersurgery.Themostcommontypeofhormonetherapyistamoxifen,whichistakenorallyforfiveyears.Othertypesofhormonetherapyincludearomataseinhibitors,whichareusedinpostmenopausalwomen,andovariansuppression,whichisusedinpremenopausalwomen.

TargetedtherapyisusedforHER2-positivebreastcancer,whichaccountsforapproximately20%ofallbreastcancers.HER2isaproteinthatisoverexpressedinsomebreastcancercellsandpromotestheirgrowth.TargetedtherapyworksbytargetingHER2andslowingorstoppingthegrowthofcancercells.Themostcommontypeoftargetedtherapyistrastuzumab,whichisgivenintravenouslyforoneyear.

Inconclusion,breastcancerisacomplexdiseasethatrequiresamultidisciplinaryapproachtotreatment.Neoadjuvantchemotherapyisanimportanttreatmentstrategythatcanhelpshrinktumorsandimproveoutcomesforpatients.Withthedevelopmentoftargetedtherapyandpersonalizedmedicine,thefutureofbreastcancertreatmentlookspromising.However,itisimportanttocontinueresearchandworktowardsfindingnewandmoreeffectivetreatmentsforalltypesofbreastcancerBreastcanceristhemostcommoncanceramongwomenworldwide,anditsincidencehasbeenincreasingoverthepastfewdecades.Thediseaseishighlycomplex,anditsmanagementrequiresamultidisciplinaryapproach.Inrecentyears,neoadjuvanttherapyhasemergedasanimportanttreatmentstrategyforbreastcancer.Thisapproachinvolvesadministeringchemotherapyortargetedtherapybeforesurgerytoshrinkthesizeofthetumorandincreasetheefficacyofsurgery.

Neoadjuvantchemotherapyistypicallyusedforpatientswhohavelocallyadvancedbreastcancerortumorsthataretoolargetoberemovedsurgicallywithoutcausingsignificantcosmeticorfunctionaldamage.Insomecases,neoadjuvantchemotherapycanconverttumorstoasmallersize,allowingbreast-conservingsurgeryinsteadofmastectomy.Thisapproachhasshowntoimproveoutcomes,withstudiesreportingahigherrateofcompletetumorresponse,reducedtumorsize,andimprovedsurgicaloutcomes.

Targetedtherapyisaformofcancertreatmentthatinvolvestheuseofdrugsorothersubstancesthatspecificallytargetcancercells.Unlikechemotherapy,whichtargetsallrapidlydividingcellsinthebody,targetedtherapyisdesignedtodisruptspecificmoleculesorsignalingpathwaysthatareessentialforcancercellgrowthandsurvival.Targetedtherapyhasrevolutionizedbreastcancertreatment,andmanydrugshavebeendevelopedspecificallytotargetdifferentsubtypesofbreastcancer.

OnesuchexampleistheuseoftrastuzumabforHER2-positivebreastcancer.HER2isagrowth-promotingproteinthatisoverexpressedinapproximately20%ofbreastcancers.TrastuzumabisamonoclonalantibodythatbindstoHER2,preventingitssignalingandpromotingcancercelldeath.Theuseoftrastuzumabinneoadjuvanttherapyhasshowntoimproveoutcomesandincreasetherateofcompletetumorresponse.

Personalizedmedicineisanemergingapproachtocancertreatmentthatinvolvestailoringtreatmenttoindividualpatientsbasedontheiruniquemolecularprofile.Withadvancesingenomics,itisnowpossibletoidentifymutationsorothergeneticalterationsthatdrivecancergrowthandprogression.Thisinformationcanbeusedtoselectthemostappropriatetreatmentforeachpatient.Thisapproachhasshownpromisein