復(fù)發(fā)或轉(zhuǎn)移性乳腺癌治療的選擇課件整理

復(fù)發(fā)或轉(zhuǎn)移性乳腺癌治療的選擇復(fù)發(fā)或轉(zhuǎn)移性乳腺癌治療的選擇復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的現(xiàn)狀大部分轉(zhuǎn)移性乳腺癌是早期乳腺癌治療后復(fù)發(fā)的病例<10%初診時(shí)即為轉(zhuǎn)移性乳腺癌常見的轉(zhuǎn)移部位是骨、肝、肺和中樞神經(jīng)系統(tǒng)50-75%患者僅有單一臟器受累全乳切除術(shù)后局部復(fù)發(fā)通常發(fā)生于胸壁及表面的皮膚這些患者中25%-30%出現(xiàn)遠(yuǎn)處轉(zhuǎn)移復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療目標(biāo)控制腫瘤相關(guān)癥狀提高生活質(zhì)量，改善無(wú)進(jìn)展生存期延長(zhǎng)總生存

晚期轉(zhuǎn)移性乳腺癌的治療選擇

細(xì)胞毒藥物蒽環(huán)類紫杉類卡培他濱長(zhǎng)春瑞濱吉西他濱

激素類藥物三苯氧胺芳香化酶抑制劑FulvestrantLHRH拮抗劑靶向治療

EGFR抑制:Trastuzumab,Pertuzumab?T-DM1?

信號(hào)傳導(dǎo)抑制劑:Lapatinib

Gefetinib?Erlotinib?

血管生成抑制劑:Bevacizumab雙磷酸鹽類支持與姑息治療復(fù)發(fā)或轉(zhuǎn)移性乳腺癌治療指南(NCCN2011-2)內(nèi)分泌治療化療靶向治療靶向治療復(fù)發(fā)或轉(zhuǎn)移性乳腺癌治療策略復(fù)發(fā)或轉(zhuǎn)移性乳腺癌ER和或PR陽(yáng)性內(nèi)分泌治療ER和或PR陰性化療內(nèi)分泌治療失敗HER2陽(yáng)性化療+曲妥珠單抗HER2陰性化療化療+拉帕替尼ASCO2010.USOncology

(IHC3+population)0 9.一般狀況較差，無(wú)癥狀的轉(zhuǎn)移的患者，可能更從單藥序貫治療中獲益。Chemotherapy0 10 20 30 40 50 60 70ASCO2010.(chemotherapeutic,hormonal,orbiological),*6mg用于絕經(jīng)前/圍絕經(jīng)期

晚期乳腺癌：Ⅲ期臨床試驗(yàn)復(fù)發(fā)或轉(zhuǎn)移性乳腺癌首選化療方案1st-line

HerceptinJClinOncol2008;26(24):X-X.蒽環(huán)、紫彬、Trastuzumab治療失敗患者XT(n=255) 42%Paridaensetal.Avastin+paclitaxel

E21002005VagelT11426;FISH+353.Totalresponses(%)<10%初診時(shí)即為轉(zhuǎn)移性乳腺癌000125.復(fù)發(fā)或轉(zhuǎn)移性乳腺癌治療細(xì)胞毒藥物化療內(nèi)分泌治療生物靶向治療局部治療姑息治療復(fù)發(fā)或轉(zhuǎn)移性乳腺癌化療適應(yīng)癥DFS較短存在廣泛轉(zhuǎn)移,特別是內(nèi)臟轉(zhuǎn)移（肝,肺）疾病迅速進(jìn)展內(nèi)分泌治療無(wú)效復(fù)發(fā)或轉(zhuǎn)移性乳腺癌化療

RR（CR)1960’s非蒽環(huán)類藥單藥化療20～40％（0）1970’s非蒽環(huán)類藥聯(lián)合化療50%（10％）70’末蒽環(huán)類藥單藥化療30～50％(10％）1980’s含蒽環(huán)類藥聯(lián)合化療50～70％（10～15％）1990’s紫杉類及其聯(lián)合方案，60％～80％（15％）化療＋靶向治療

復(fù)發(fā)或轉(zhuǎn)移性乳腺癌首選化療藥物蒽環(huán)類多柔比星表柔比星脂質(zhì)體多柔比星紫杉類紫杉醇多西他賽白蛋白結(jié)合的紫杉醇健擇?卡培他濱長(zhǎng)春瑞濱

復(fù)發(fā)或轉(zhuǎn)移性乳腺癌首選化療方案CMF(CTX+MTX+5FU)CAF/FAC(CTX+ADM+5FU)CEF/FEC(CTX/EPI+5FU)AC(ADM+CTX)EC(EPI+CTX)AT(ADM+DTX，ADM+PTX)GT(GEM+PTX)XT(Xel+DTX)AvsTvsATTTFOS復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的化療

蒽環(huán)類和紫杉類目前最有效的乳腺癌化療方案之一適用于未用過蒽環(huán)類和紫杉類的復(fù)發(fā)轉(zhuǎn)移患者，如CMF輔助治療失敗乳腺癌患者復(fù)發(fā)轉(zhuǎn)移患者中應(yīng)用機(jī)會(huì)不多蒽環(huán)類成為輔助治療基本藥物后，復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的一線治療？XDvsD:SurvivalO’ShaughnessyJ,etal.JClinOncol,2002;20:2812-2823.TTP

OSXT(n=255) 42%

T

(n=256) 30%ORRp=0.0060612182430364248 1.00.80.60.40.20.0OverallSurvivalTime(months)G,GEM;T,PTX;lbainetal.JClinOncol2008;26(24):X-X.與紫杉醇相比，健擇?聯(lián)合紫杉醇可顯著延長(zhǎng)OS18219518.6(16.6,20.7)15.8(14.4,17.4)TGTN

Events

Median(95%CI)266263HR=0.82(95%CI:0.67,1.00)Logrankp=0.0489ProbabilityHR=0.70(95%CI:0.59,0.85)Logrankp=0.0002Events227237Median(95%CI)6.1(5.3,6.7)4.0(3.5,4.4)06121824303642 481.00.80.60.40.20.0MonthsTGTProbabilityAlbainetal.JClinOncol2008;26(24):X-X.與紫杉醇相比，健擇?聯(lián)合紫杉醇可顯著延長(zhǎng)TTP

與紫杉醇相比，健擇?聯(lián)合紫杉醇可顯著提高ORRGTArm

(N=266)TArm

(N=263)CR(%)7.94.6PR(%)33.521.7Totalresponses(%)41.426.295%CI

(35.4,47.3)(20.9,31.6)p-value0.0002Albainetal.JClinOncol2008;26(24):X-X..健擇?聯(lián)合多西紫杉醇vs.卡培他濱聯(lián)合多西紫杉醇:

PFS相近ProgressionFreeSurvival(months)

N

Events

Median(95%CI)53 151 8.05(6.60,8.71)152 142 7.98(6.93,8.77)Logrankp=0.121HR=1.20(95%CI:0.96,1.50)GD

CD0 10203040 50Probability1.00.80.60.40.20.0D,DTX;G,GEM;C,CapeChanSetal.Presentedat:SanAntonioBreastCancerConference,December13-16,2007;SanAntonio,Texas.20*InvestigatorassessedGDArm

(N=153)CDArm(N=152)p-valueORR*,%32320.931CR,%53PR,%2729MedDR,mos7.759.070.047MedTTF,mos4.244.070.059MedOS,mos19.2921.450.983健擇?聯(lián)合多西紫杉醇vs.卡培他濱聯(lián)合多西紫杉醇:

ORR,TTF,OSChanSetal.Presentedat:SanAntonioBreastCancerConference,December13-16,2007;SanAntonio,Texas.健擇?聯(lián)合多西紫杉醇→卡培他濱vs.

卡培他濱聯(lián)合多西紫杉醇→健擇?GD→C較CD→G方案二線治療階段及總的TTP更長(zhǎng)注：健擇?在中國(guó)批準(zhǔn)的適應(yīng)癥為聯(lián)合紫杉醇治療復(fù)發(fā)或轉(zhuǎn)移性乳腺癌健擇?聯(lián)合多西紫杉醇vs.Jonesetal.Jonesetal.目前最有效的乳腺癌化療方案之一Anastrozole

1mg蒽環(huán)、紫彬、Trastuzumab治療失敗患者StudyRegimenNo.RR（CR)ORR(95%CI)28.FranciscoJ.ProbabilityMartyetal.):24s(Abstract581);MelemedAS,etal.AbstractCRA1004.Abstract1005.(first-line)與紫杉醇相比，健擇?聯(lián)合紫杉醇可顯著延長(zhǎng)TTPTrastuzumab治療HER2陽(yáng)性轉(zhuǎn)移性乳腺癌方案存在廣泛轉(zhuǎn)移,特別是內(nèi)臟轉(zhuǎn)移（肝,肺）25mg

vsTAM存在廣泛轉(zhuǎn)移,特別是內(nèi)臟轉(zhuǎn)移（肝,肺）Martyetal.2005紫杉醇+健擇紫杉醇

+赫賽汀多西紫杉醇+健擇

紫杉類各種治療方案治療轉(zhuǎn)移性乳腺癌的RR多西紫杉醇+赫賽汀單藥多西紫杉醇多西紫杉醇＋希羅達(dá)Slamonetal.2001Melemedetal.2007E21002007紫杉醇

+貝伐Jonesetal.2005Melemedetal.2007E21002007Slamonetal.2001Jonesetal.2005Martyetal.2005O’Shaughnessyetal.2002O’Shaughnessyetal.2002Chanetal.2005Chanetal.2005*********僅包括有可測(cè)量病灶的患者SlamonDJ,etal.NEnglJMed2001;344:783–92;O’ShaughnessyJ,etal.JClinOncol2002;20:2812–23;JonesSE,etal.JClinOncol2005;23:5542–51;MartyM,

etal.JClinOncol2005;23:4265–74;ChanS,etal.JClinOncol2005;23

(June1suppl.):24s(Abstract581);MelemedAS,etal.PresentedatASCOBreastCancer2007;AvastinSummaryofProductCharacteristics客觀緩解率(%)單藥紫杉醇 0 10 20 30 40 50 60 70

各種方案治療轉(zhuǎn)移性乳腺癌的PFSDocetaxel

Chan1999Doxorubicin

Chan1999Paclitaxel

Seidman2004Vinorelbine

Muhoz2006Doxorubicin+paclitaxel

Jassem2001Capecitabine+docetaxel

O’Shaughnessy2002Gemcitabine+paclitaxel

Albain2004Fluorouracil+epirubicin

Zielinski2005Gemcitabine+vinorelbine

Mu?oz2006Epirubicin+taxane

Pacilio2006Avastin+paclitaxel

E21002005Paclitaxel

E210020050 2 4 6 8 10 12 14MonthsMonotherapyCombination

chemotherapychemotherapy

+targetedtherapyMedianPFS/TTP9monthsEMEAAvastinEuropeanPublicAssessmentReport,2007Patientswithheavilypretreatedlocallyrecurrentormetastaticbreastcancer(N=762)EribulinMesylate1.4mg/m22-5minIVonDays1,8

q3w(n=508)TreatmentofPhysician’sChoice(TPC)Anymonotherapyapprovedforcancertreatment(chemotherapeutic,hormonal,orbiological),*orsupportivecareonly?(n=254)Randomized2:1;stratifiedby

geographicregion,previouscapecitabinetreatment,HER2/neustatusTwelvesC,etal.ASCO2010.AbstractCRA1004.EMBRACE:Randomized,Open-LabelPhaseIIITrial(PrimaryEndpointOS)

*FDAapprovedforthetreatmentofcancer.?Palliativetreatmentorradiotherapyaccordingtolocalpractice.96%ofpatientsinTPCarmreceivedchemotherapyTwelvesC,etal.ASCO2010.AbstractCRA1004.EMBRACE:OverallandProgression-FreeSurvival(ITT)OutcomeEribulin(n=508)Physician’sChoice(n=254)MedianOS(independentreview),mos13.1210.65HR(95%CI)0.81(0.66-0.99)

Pvalue.0411-yrsurvival,%53.943.7MedianPFS(independentreview),mos3.72.2HR(95%CI)0.87(0.71-1.05)Pvalue.14MedianPFS(investigatorreview),mos3.62.2HR(95%CI)0.76(0.64-0.90)Pvalue.002晚期轉(zhuǎn)移性乳腺癌選用一線化療方案輔助治療僅用內(nèi)分泌治療而未用化療的患者可以選擇CMF,CAF,AC方案。輔助治療未用過蒽環(huán)類和/或紫杉類化療的患者或雖用過但臨床判定未耐藥或治療失敗者,首選AT方案。蒽環(huán)類輔助治療失敗者，首選健擇?聯(lián)合紫杉醇方案和卡培他濱聯(lián)合多西紫杉醇方案。紫杉類輔助治療失敗的患者，目前尚無(wú)標(biāo)準(zhǔn)治療方案，可以考慮的藥物有Cape、NVB、健擇?和鉑類，采取單藥或聯(lián)合化療。單藥序貫化療？聯(lián)合化療？單藥序貫化療或聯(lián)合化療聯(lián)合化療客觀緩解率較高，至疾病進(jìn)展時(shí)間較長(zhǎng)，但是毒性較大，目前沒有強(qiáng)有力的證據(jù)證實(shí)生存獲益。一般狀況好，疾病進(jìn)展較快或有內(nèi)臟轉(zhuǎn)移的患者，可能從更強(qiáng)的聯(lián)合化療中受益。一般狀況較差，無(wú)癥狀的轉(zhuǎn)移的患者，可能更從單藥序貫治療中獲益。晚期轉(zhuǎn)移性乳腺癌治療細(xì)胞毒藥物化療內(nèi)分泌治療生物靶向治療局部治療姑息治療(%)P(M)P(M)PAromataseInhibitorCapecitabine+docetaxel

O’Shaughnessy2002ORR(95%CI)28.Fluorouracil+epirubicin

Zielinski2005蒽環(huán)類成為輔助治療基本藥物后，復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的一線治療？20(95%CI:0.AC(ADM+CTX)復(fù)發(fā)或轉(zhuǎn)移性乳腺癌首選化療方案EMILIAIII580(2線)T-DM1PFS隨機(jī)Bangemannetal.70’末蒽環(huán)類藥單藥化療30～50％(10％）(chemotherapeutic,hormonal,orbiological),*monotherapy復(fù)發(fā)或轉(zhuǎn)移性乳腺癌治療與紫杉醇相比，健擇?聯(lián)合紫杉醇可顯著提高ORRvsC+LSafety1st-line

HerceptinUSOncology

(IHC3+population)內(nèi)分泌治療內(nèi)分泌治療藥物部分抗雌激素藥物-選擇性雌激素受體調(diào)節(jié)劑他莫昔芬芳香化酶抑制劑非甾體類：阿那曲唑，來(lái)曲唑甾體類：依西美坦雌激素受體抑制劑氟維司群LHRH類似物戈舍瑞林孕激素甲地孕酮哈里森腫瘤學(xué)手冊(cè).人民軍醫(yī)出版社2010年9月第一版.Anti-AromataseAgentsvsTamoxifenin1stLine

TherapyofAdvancedBreastCancer:SummaryExemestane

25mg

vsTAMAnastrozole

1mgvsTAMLetrozole2.5mgvsTAMNo.ofpatientsCR+PR,%

61vs5944vs14325vs32621.1vs17453vs45430vs20*Clin.Benefit,% 55vs39* 59.1vs45.6* 49vs38*MedianTTP,mo

8.9vs5.2

8.5vs7.0

9.4vs6.0*

OS:notsignificant,*P<0.05ReportedatSABCS2001IndirectComparison:AIsvsTamoxifenasFirst-lineTreatmentofABCRefNORR%P1TAMvsLET90721vs320.0022TAMvsANA102127vs29NS3TAMvsEXE38229vs44NI1.Mouridsenetal.JClinOncology2003;21:2101–92.Bonneterreetal.Cancer2001;92:2247–583.Paridaensetal.ProcASCO2004;23:6(Abstract575)32戈舍瑞林3.6mg用于絕經(jīng)前/圍絕經(jīng)期

晚期乳腺癌：Ⅲ

期臨床試驗(yàn)參考文獻(xiàn)客觀緩解率(%)中位生存期

TaylorCW,etal

戈舍瑞林3.6mg 卵巢切除術(shù) 戈舍瑞林3.6mg 卵巢切除術(shù)JClinOncol (n=29*) (n=30*) (n=69) (n=67)

1998;16:994–9. 31 27 37月 33月

BoccardoF,etal

戈舍瑞林3.6mg 卵巢切除術(shù) 戈舍瑞林3.6mg 卵巢切除術(shù)

AnnOncol

或卵巢照射 或卵巢照射

1994;5:337–42. (n=22*) (n=15*) (n=24) (n=18) 27(+19) 47(+25) 36月 38月JonatW,etal

戈舍瑞林3.6mg 戈舍瑞林3.6mg 戈舍瑞林3.6mg 戈舍瑞林3.6mg+

EurJCancerPartA +三苯氧胺 三苯氧胺

1995;31A:137–42.

(n=159) (n=159) (n=159) (n=159)

31 38 29月 32月*

可評(píng)價(jià)病例復(fù)發(fā)或轉(zhuǎn)移性乳腺癌內(nèi)分泌治療藥物選擇不重復(fù)使用輔助治療或一線治療用過的藥物既往未用過抗雌激素治療者，仍可使用TAMTAM輔助治療失敗者，首選AI(絕經(jīng)前者卵巢去勢(shì)±AI)AI失敗者可選孕激素（如甲地孕酮）或氟維司群Lapatinib+卡培他濱治療難治轉(zhuǎn)移性乳腺癌

(EGF100151研究)(first-line)ACorPalone324.AbstractCRA1004.EMEAAvastinEuropeanPublicAssessmentReport,2007TreatmentofPhysician’sChoice(TPC)Estevaetal.HormonereceptornegativeHerceptin/chemotherapy(n=159) (n=159) (n=159) (n=159)

31 38 29月 32月StudyRegimenNo.Combination

chemotherapy復(fù)發(fā)或轉(zhuǎn)移性乳腺癌首選化療藥物AC(ADM+CTX)Probability27(+19) 47(+25) 36月 38月NEnglJMed2001;344:783–92;O’ShaughnessyJ,etal.HR(95%CI)復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的化療

蒽環(huán)類和紫杉類Trastuzumab+vsT+C晚期轉(zhuǎn)移性乳腺癌治療細(xì)胞毒藥物化療內(nèi)分泌治療生物靶向治療局部治療姑息治療

StudyRegimenNo.RRMTTPMST(%)P(M)P(M)PSlamonACorP+Tvs.46950vs.<0.00017.4vs.<0.000125.1vs.0.046(first-line)ACorPalone324.020.3MartyD+Tvs.18661vs.0.00211.7vs.0.000131.2vs.0.033(first-line)Dalone346.122.7CobleighT222159.1(MRT)13(pretreated)VagelT11426;FISH+353.824.4(first-line)

ASCO2006June2-6

HER2陽(yáng)性轉(zhuǎn)移性乳腺癌的治療Trastuzumab一線治療HER2陽(yáng)性乳腺癌Carbo,carboplatinMonthsH+PP

onlyH+DD

onlyHP

CarboP

CarboH0648g

(IHC3+population)M77001USOncology

(IHC3+population)Martyetal2005;Robertetal2006;Smithetal2001Trastuzumab治療HER2陽(yáng)性轉(zhuǎn)移性乳腺癌方案Trastuzumab

聯(lián)合紫杉醇（每周）Trastuzumab一線單藥聯(lián)合長(zhǎng)春瑞賓ORR:75%ORR:35%ORR:83%聯(lián)合卡培他濱聯(lián)合多西紫杉醇ORR:73%ORR:53-62%Seidmanetal95PtnsG.Fountzilasetal.34PtnsTsavdaridisetal.28PtnsBurrisetal.16PtnsEstevaetal.30PtnsFranciscoJ.etal.30PtnsBursteinetal.40PtnsJahanzebetal.29PtnsBangemannetal.13PtnsCharlesLetal.114Ptns

Brufskyetal2005Trastuzumab

:equallyeffectiveinhormonereceptor-negativeand-positivediseaseHerceptin/chemotherapyChemotherapy1st-line

Herceptin2nd-/3rd-line

HerceptinSlamonetalVogeletalCobleighetalOverallresponserate(%)HormonereceptorpositiveHormonereceptornegativeEvidenceofbenefitfromTrastuzumabinmultiplelinesBartschetal2006Overallresponserate(%)HER2-positivediseaseisnotrefractory

tomultiplelinesofHerceptinTrastuzumab+anastrozole

(TAnDEM試驗(yàn))：PFS

103483117141311941100A+H10436229542100000AProbability1.00.80.60.40.2051015202530354045505560Months95%CI3.7,7.02.0,4.6pvalue0.0016MedianPFS4.8months2.4monthsEvents87990.0No.atriskPFS,timefromrandomisationtodateofprogressivediseaseordeath

An,anastrozole;CI,confidenceinterval;HR,hazardratioKaufmanetal2006Trastuzumab+anastrozole

(TAnDEM試驗(yàn))：ORRPatients

(%)A+H(n=74)A(n=73)p=0.018PR,partialresponse;SD,stabledisease(>6months);PD,progressivedisease0102030405060PRSDPD6.8%20.3%38.4%37.8%40.5%49.3%Kaufmanetal2006

Trastuzumab+ChemotherapyCurrenttherapeuticcascadeinHER2+MBCHER2+/ER+MBCGoodperformancestatusVisceraldiseaseRapidlyprogressingPoorperformancestatusNonvisceraldiseaseSlowprogression

Trastuzumabmonotherapy

Trastuzumab+AromataseInhibitorPriorA.I.?YESNOLapatinib+卡培他濱治療難治轉(zhuǎn)移性乳腺癌

(EGF100151研究)Lap+卡培他濱N=160卡培他濱N=161病人數(shù)160161進(jìn)展或死亡60(38%)78(48%)中位PFS(月)8.44.4HazardRatio(95%CI)0.49(0.34-0.71)P值(log-rank,1-side)<0.001蒽環(huán)、紫彬、

Trastuzumab治療失敗患者ORR(95%CI)28.8%(21.9-36.4)16.1%(10.8-22.8)p值(Fisher,sexact,2-sided)0.0174)16.1980’s含蒽環(huán)類藥聯(lián)合化療50～70％（10～15％）OS:notsignificant,*P<0.NEventsMedian(95%CI)4)16.單藥序貫化療或聯(lián)合化療復(fù)發(fā)或轉(zhuǎn)移性乳腺癌治療蒽環(huán)、紫彬、Trastuzumab治療失敗患者與紫杉醇相比，健擇?聯(lián)合紫杉醇可顯著延長(zhǎng)OSSlamonACorP+Tvs.Trastuzumab一線治療HER2陽(yáng)性乳腺癌Patients

(%)Melemedetal.注：健擇?在中國(guó)批準(zhǔn)的適應(yīng)癥為聯(lián)合紫杉醇治療復(fù)發(fā)或轉(zhuǎn)移性乳腺癌6mg+

EurJCancerPartA +三苯氧胺 三苯氧胺

1995;31A:137–42.ASCO2010.ASCO2010.Cancer2001;92:2247–58Combination

chemotherapyLogrankp=0.貝伐單抗聯(lián)合化療一線治療轉(zhuǎn)移性乳腺癌的三個(gè)隨機(jī)臨床試驗(yàn)的薈萃分析AVADO多西紫杉醇E2100紫杉醇RIBBON-1,2卡培他濱，紫杉類或蒽環(huán)類隨機(jī)入組僅化療化療+貝伐單抗直至進(jìn)展選擇性二線治療：化療+貝伐單抗（AVADO和RIBBON-1）初治的轉(zhuǎn)移性乳腺癌JoyceO'Shaughnessyetal,ASCO2010,abs1005O’ShaughnessyJ,etal.ASCO2010.Abstract1005.貝伐單抗聯(lián)合化療一線治療轉(zhuǎn)移性乳腺癌的三個(gè)隨機(jī)臨床試驗(yàn)的薈萃分析OutcomeChemotherapy+Bevacizumab(n=1439)ChemotherapyAlone(n=1008)MedianPFS,mos9.26.7HR(95%CI)0.64(0.57-0.71)ORR,*%4932MedianOS,mos26.726.4HR(95%CI)0.97(0.86-1.08)1-yrOS,%8277*Assessedinpatientswithmeasurablediseaseatbaseline:n=1105forchemotherapyplusbevacizumab;n=788forchemotherapyalone.正在進(jìn)行HER陽(yáng)性