LaRicercaItalianaCarcinomadellaMammella

PPronzato

Genova,13.1.2017

BACKFROMSANANTONIO2017

(Italian)Research

•  BasicandTranslaFonalResearch•  DesignandConductofClinicalTrials(noprofit)•  LeadershipinPHARMAsponsoredTrials

•  ParFcipaFonwithmajorinvolvementinthebestInternaFonalGroups

•  EpidemiologicalResearch

ItalianResearch:makessense?

•  BasicandTranslaFonalResearch•  DesignandConductofClinicalTrials(noprofit)•  LeadershipinPHARMAsponsoredTrials

•  ParFcipaFonwithmajorinvolvementinthebestInternaFonalGroups

•  EpidemiologicalResearch

.....DesignedandConductedinItaly

SanAntonio&SABCS

SanAntonio,Texas

SABCS2016

ItalianResearchintheContextALookBack

KeyPoints

SorryforLeavingApart

•  MRIRole•  ChemoprevenFon

•  ClinicalCorrelaFonsofPathologicalandBiomolecularFindings

•  FerFlityPreservaFon•  TreatmentStrategyofMBC

FSardanelli,EurJRadiol2012;ADecensi,AnnOncol2013;GViale,AnnOncol2010-2011-2012;LDelMastro,JAMA2011;AGennari,JCO2011;ADiLeo,JNCI2014

EarlyBreastCancerTreatment

•  ConservaFveSurgery•  Follow-Up•  EvoluFonofAdjuvantHormonotherapy•  EvoluFonofAdjuvantChemotherapy• Neo-AdjuvantTherapy

TheBreastConservaFonStrategy

Surgery

UVeronesi,NEJM2002&2003

TheFollow-UpStrategy

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

DFS

M Rosselli del Turco, JAMA 1994

+10months

EvoluFonofHormonotherapy

EBCTCG,Lancet2015;CDavies,Lancet2013

10-yrTamvs5-yrAI

EBCTCG,Lancet2015;CDavies,Lancet2013

10-yrTamvs5-yrAI

NotonlyContribuFontoEBCTCG,BIG,ATAC,IES,SOFT,TEXT-SOFT,etc

HTasanalternaFvetoCTAISupremacySequenceorCombinaFonofCTandHT

EvoluFonofChemotherapy

PresentedbyTTrainaatASCO2016

PresentedbyTHBursteinatASCO2015

GIM-2OpFmizingAdjuvantChemotherapy

LDelMastro,Lancet2015

TheNeo-AdjuvantTherapy

LessonsFromNeoadjuvantTrials

LGianni,LancetOncol2012–2016;seealsoVGuarneri,JCO2012-2014

ItalianResearchintheContext

MovingForward

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

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

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

Basic(2016News)

SNik-Zainal,Nature2016;PMer[ns,Nature2016;RMarcoQe,Cell2016;NVJordan,Nature2016;SShu,Nature2016;FBrasò-Maristany,NatMed2016;DHoriuchi,NatMed2016

Basic(2016News)

SNik-Zainal,Nature2016;PMer[ns,Nature2016;RMarcoQe,Cell2016;NVJordan,Nature2016;SShu,Nature2016;FBrasò-Maristany,NatMed2016;DHoriuchi,NatMed2016

Basic(2016News)

SNik-Zainal,Nature2016;PMer[ns,Nature2016;RMarcoQe,Cell2016;NVJordan,Nature2016;SShu,Nature2016;FBrasò-Maristany,NatMed2016;DHoriuchi,NatMed2016

Basic(2016News)

SNik-Zainal,Nature2016;PMer[ns,Nature2016;RMarcoQe,Cell2016;NVJordan,Nature2016;SShu,Nature2016;FBrasò-Maristany,NatMed2016;DHoriuchi,NatMed2016

Basic(2016News)

JSeQleman,Nature2016

Basic(2016News)

SNik-Zainal,Nature2016;PMer[ns,Nature2016;RMarcoQe,Cell2016;NVJordan,Nature2016;SShu,Nature2016;FBrasò-Maristany,NatMed2016;DHoriuchi,NatMed2016

TranslaFonal(2016News)

CFribbens,JCO2016

TranslaFonal(2016News)

CFribbens,JCO2016

TranslaFonal(2016News)

JBaselga,JCO2014;SLuen,LancetOncol2017

TranslaFonal(2016News)

JBaselga,JCO2014;SLuen,LancetOncol2017

Clinical(2016News)

•  MINDACT

•  RiskofLateRelapse(EBCTCG)•  MA17-RandOthers

•  PALOMA-2andMONALEESA-2

•  FALCON

FCardoso,NEJM2016;EBCTCG,ASCO2016;PGoss,NEJM2016;RSFinn,NEJM2016;GNHortobagyiNEJM2016;JFRoberson,Lancet2017;EAPerez,JCO2017

PresentedbyEWineratSABCS2016

PresentedbyEWineratSABCS2016

Overtreatment

Sound

PIPVeronesi

SINODARONE

T1-T2cN0(ancheETG)NoNACTMTSalLinfonodoSenFnella

PICTinterri

Radiotherapy

LLivi,EJC2015;PresentedalsobyIMea_niatSABCS2016

ShortHer

PIPFConte

KRONOS

PresentedbyCZanagniatSABCS2016

SNAP

PresentedbyAGennariatSABCS2016

FEVEX

PIGArpino

Resistance

GIM-4

PILDelMastro

GIM-10CONSENT

PILDelMastro

NAP-HER

PresentedbyLGianniatSABCS2016

ETNA

PresentedbyLGianniatASCO2016

AdjuvantImmunotherapy

HealthEquity

AMBRA

PresentedbyGMustacchiatSABCS2016

T-DM1inCommonPracFce

PresentedbyAFabiatSABCS2016

Conclusions

ComplexityofRCTs

MRosenblaQ,NEJM2017

NeraFnib

MMarFn,LancetOncology2016

I-SPY

JWPark,NEJM2016

BayesianBasket

LTrippa,JCO2017

I-SPY

JWPark,NEJM2016

NewOpportuniFes

•  ClinicalTrialsRegulaFonEU536/2014•  BreastUnitsandOncologicalNetworks•  ACCOncogenomicProject

ExploitNEO

SURGERY

DRUGTHERAPY

NORD RD

NopCR

CTC/cTDNA

DRUGTHERAPY2

ExploitNEO

SURGERY

DRUGTHERAPY

NORD RD

NopCR

CTC/cTDNA

DRUGTHERAPY2

MutaFonalAnalysisofsingleCTC

FDeLuca,Oncotarget2016

Trajectories

EReed,BMJPall&Supp2013

BACK-UP

MRosenblaQ,NEJM2017

ExploitNEO

SURGERY

DRUGTHERAPY

NORD RD

NopCR

CTC/cTDNA

ExploitNEO

SURGERY

DRUGTHERAPY

NORD RD

NopCR

CTC/cTDNA

DRUGTHERAPY2

ExploitNEO

SURGERY

DRUGTHERAPY

NORD RD

NopCR

CTC/cTDNA