la ricerca italiana carcinoma della mammella · 2017-02-07 · la ricerca italiana carcinoma della...
TRANSCRIPT
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LaRicercaItalianaCarcinomadellaMammella
PPronzato
Genova,13.1.2017
BACKFROMSANANTONIO2017
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(Italian)Research
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• BasicandTranslaFonalResearch• DesignandConductofClinicalTrials(noprofit)• LeadershipinPHARMAsponsoredTrials
• ParFcipaFonwithmajorinvolvementinthebestInternaFonalGroups
• EpidemiologicalResearch
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ItalianResearch:makessense?
• BasicandTranslaFonalResearch• DesignandConductofClinicalTrials(noprofit)• LeadershipinPHARMAsponsoredTrials
• ParFcipaFonwithmajorinvolvementinthebestInternaFonalGroups
• EpidemiologicalResearch
.....DesignedandConductedinItaly
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SanAntonio&SABCS
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SanAntonio,Texas
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SABCS2016
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ItalianResearchintheContextALookBack
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KeyPoints
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SorryforLeavingApart
• MRIRole• ChemoprevenFon
• ClinicalCorrelaFonsofPathologicalandBiomolecularFindings
• FerFlityPreservaFon• TreatmentStrategyofMBC
FSardanelli,EurJRadiol2012;ADecensi,AnnOncol2013;GViale,AnnOncol2010-2011-2012;LDelMastro,JAMA2011;AGennari,JCO2011;ADiLeo,JNCI2014
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EarlyBreastCancerTreatment
• ConservaFveSurgery• Follow-Up• EvoluFonofAdjuvantHormonotherapy• EvoluFonofAdjuvantChemotherapy• Neo-AdjuvantTherapy
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TheBreastConservaFonStrategy
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Surgery
UVeronesi,NEJM2002&2003
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TheFollow-UpStrategy
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EndpointsofFollow-Up
EndpointGIVIO RossellidelTurco Kokko Joseph
OverallSurvival
NoDifference NoDifference NoDifference NoDifference
QoLduringFU NoDifference NotAssessed NotAssessed NotAssessed
M Rosselli del Turco, JAMA 1994; D Palli, JAMA 1999; GIVIO, JAMA 1994; R Kokko, BCRT 2005; E Joseph, Ann Surg Oncol 1998
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DFS
M Rosselli del Turco, JAMA 1994
+10months
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EvoluFonofHormonotherapy
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EBCTCG,Lancet2015;CDavies,Lancet2013
10-yrTamvs5-yrAI
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EBCTCG,Lancet2015;CDavies,Lancet2013
10-yrTamvs5-yrAI
NotonlyContribuFontoEBCTCG,BIG,ATAC,IES,SOFT,TEXT-SOFT,etc
HTasanalternaFvetoCTAISupremacySequenceorCombinaFonofCTandHT
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EvoluFonofChemotherapy
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PresentedbyTTrainaatASCO2016
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PresentedbyTHBursteinatASCO2015
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GIM-2OpFmizingAdjuvantChemotherapy
LDelMastro,Lancet2015
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TheNeo-AdjuvantTherapy
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LessonsFromNeoadjuvantTrials
LGianni,LancetOncol2012–2016;seealsoVGuarneri,JCO2012-2014
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ItalianResearchintheContext
MovingForward
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Basic(2016News)
• NormalandNeoplasFcStemCells– MammaryCellHyerarchy– TumorCell-of-OriginandHeterogeneity– Rank-L,NF-kB,HistoneH1.0,PKA
• Genomic/ProteomicLandscape• MechanismsofMetastasis– RegulaFonofPrometastaFcProteins– MetastaFcReacFvaFon– ImmuneEvasion– ContribuFonofNeutrophils
ENolan,NatureMed2016;ASau,Cell2016;CMoralesTorres,Science2016;DRPaQabiraman,Science2016
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Basic(2016News)
• NormalandNeoplasFcStemCells– MammaryCellHyerarchy– TumorCell-of-OriginandHeterogeneity– Rank-L,NF-kB,HistoneH1.0,PKA
• Genomic/ProteomicLandscape• MechanismsofMetastasis– RegulaFonofPrometastaFcProteins– MetastaFcReacFvaFon– ImmuneEvasion– ContribuFonofNeutrophils
HGoodarzi,Cell2016;SMalladi,Cell2016;SKWeulek,CanderDiscover2016;HGao,Cell2016;QChen,Nature2016
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Basic(2016News)
• NormalandNeoplasFcStemCells– MammaryCellHyerarchy– TumorCell-of-OriginandHeterogeneity– Rank-L,NF-kB,HistoneH1.0,PKA
• Genomic/ProteomicLandscape• MechanismsofMetastasis– RegulaFonofPrometastaFcProteins– MetastaFcReacFvaFon– ImmuneEvasion– ContribuFonofNeutrophils
SNik-Zainal,Nature2016;PMer[ns,Nature2016;RMarcoQe,Cell2016;SShu,Nature2016;FBrasò-Maristany,NatMed2016;DHoriuchi,NatMed2016
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Basic(2016News)
SNik-Zainal,Nature2016;PMer[ns,Nature2016;RMarcoQe,Cell2016;NVJordan,Nature2016;SShu,Nature2016;FBrasò-Maristany,NatMed2016;DHoriuchi,NatMed2016
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Basic(2016News)
SNik-Zainal,Nature2016;PMer[ns,Nature2016;RMarcoQe,Cell2016;NVJordan,Nature2016;SShu,Nature2016;FBrasò-Maristany,NatMed2016;DHoriuchi,NatMed2016
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Basic(2016News)
SNik-Zainal,Nature2016;PMer[ns,Nature2016;RMarcoQe,Cell2016;NVJordan,Nature2016;SShu,Nature2016;FBrasò-Maristany,NatMed2016;DHoriuchi,NatMed2016
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Basic(2016News)
SNik-Zainal,Nature2016;PMer[ns,Nature2016;RMarcoQe,Cell2016;NVJordan,Nature2016;SShu,Nature2016;FBrasò-Maristany,NatMed2016;DHoriuchi,NatMed2016
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Basic(2016News)
JSeQleman,Nature2016
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Basic(2016News)
SNik-Zainal,Nature2016;PMer[ns,Nature2016;RMarcoQe,Cell2016;NVJordan,Nature2016;SShu,Nature2016;FBrasò-Maristany,NatMed2016;DHoriuchi,NatMed2016
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TranslaFonal(2016News)
CFribbens,JCO2016
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TranslaFonal(2016News)
CFribbens,JCO2016
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TranslaFonal(2016News)
JBaselga,JCO2014;SLuen,LancetOncol2017
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TranslaFonal(2016News)
JBaselga,JCO2014;SLuen,LancetOncol2017
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Clinical(2016News)
• MINDACT
• RiskofLateRelapse(EBCTCG)• MA17-RandOthers
• PALOMA-2andMONALEESA-2
• FALCON
FCardoso,NEJM2016;EBCTCG,ASCO2016;PGoss,NEJM2016;RSFinn,NEJM2016;GNHortobagyiNEJM2016;JFRoberson,Lancet2017;EAPerez,JCO2017
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PresentedbyEWineratSABCS2016
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PresentedbyEWineratSABCS2016
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Overtreatment
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Sound
PIPVeronesi
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SINODARONE
T1-T2cN0(ancheETG)NoNACTMTSalLinfonodoSenFnella
PICTinterri
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Radiotherapy
LLivi,EJC2015;PresentedalsobyIMea_niatSABCS2016
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ShortHer
PIPFConte
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KRONOS
PresentedbyCZanagniatSABCS2016
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SNAP
PresentedbyAGennariatSABCS2016
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FEVEX
PIGArpino
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Resistance
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GIM-4
PILDelMastro
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GIM-10CONSENT
PILDelMastro
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NAP-HER
PresentedbyLGianniatSABCS2016
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ETNA
PresentedbyLGianniatASCO2016
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AdjuvantImmunotherapy
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HealthEquity
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AMBRA
PresentedbyGMustacchiatSABCS2016
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T-DM1inCommonPracFce
PresentedbyAFabiatSABCS2016
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Conclusions
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ComplexityofRCTs
MRosenblaQ,NEJM2017
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NeraFnib
MMarFn,LancetOncology2016
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I-SPY
JWPark,NEJM2016
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BayesianBasket
LTrippa,JCO2017
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I-SPY
JWPark,NEJM2016
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NewOpportuniFes
• ClinicalTrialsRegulaFonEU536/2014• BreastUnitsandOncologicalNetworks• ACCOncogenomicProject
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ExploitNEO
SURGERY
DRUGTHERAPY
NORD RD
NopCR
CTC/cTDNA
DRUGTHERAPY2
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ExploitNEO
SURGERY
DRUGTHERAPY
NORD RD
NopCR
CTC/cTDNA
DRUGTHERAPY2
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MutaFonalAnalysisofsingleCTC
FDeLuca,Oncotarget2016
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Trajectories
EReed,BMJPall&Supp2013
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BACK-UP
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MRosenblaQ,NEJM2017
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ExploitNEO
SURGERY
DRUGTHERAPY
NORD RD
NopCR
CTC/cTDNA
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ExploitNEO
SURGERY
DRUGTHERAPY
NORD RD
NopCR
CTC/cTDNA
DRUGTHERAPY2
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ExploitNEO
SURGERY
DRUGTHERAPY
NORD RD
NopCR
CTC/cTDNA