Download 2017 - Breast Cancer Research Centre WA

Metastaticbreastcancer
• NewandEffectiveTherapies
• Safecomplementarytherapiesvsunprovenalternatives
• Howcanwereachthewiderbreastcancercommunity–
gettingtherightinformation.
• Whataspectsofcarecouldbeimprovedforadvanced
breastcancerpatients?
∼ NewandEffectiveTherapies∼
Howdoknowifatherapyisgoingtokillbreast
cancercells?
§ Biologicalplausibility
§ Biologicalevidence
§ Humanevidence
§ Humanproof
NewandEffectiveTherapies
Howdoknowifatherapyisgoingtokillbreast
cancercells?
Molecularlevel
§ Biologicalplausibility
ProofinCelllines/Xenografts
§ Biologicalevidence
Tumoursgetsmaller
§ Humanevidence
Ethical/Robust/Statisticallysound
§ Humanproof
“Basicmolecularbiology”
NORMALCELL
Nucleus: Stores genetic
information which directs cellular
function
Cytoplasm: Surrounds nucleus
- Provides structure
- Houses glucose for energy
- Protein manufactured
Normal growth & death
Normal cell function
BREASTCANCERCELL
Nucleus: Stores genetic
information which directs cellular
function
- Genetic mutations
- Excessive genetic information
Cytoplasm: Surrounds nucleus
- Ability to invade
- Houses endless energy
- “Bad” protein manufactured
Abnormal growth, Doesn’t die
Abnormal function
- Invades into blood vessels
- Damages surrounding cells
NewandEffectiveTherapies
Howdoknowifatherapyisgoingtokillbreast
cancercells?
Molecularlevel
§ Biologicalplausibility
ProofinCelllines/Xenografts
§ Biologicalevidence
Measurablereductiontumour
§ Humanevidence
Ethical/Robust/Statisticallysound
§ Humanproof
ER
P
P
P
P ER
ER
ERE
p160
CBP
Basal
transcription
machinery
ER target gene transcription
NewandEffectiveTherapies
Howdoknowifatherapyisgoingtokillbreast
cancercells?
Molecularlevel
§ Biologicalplausibility
ProofinCelllines/Xenografts
§ Biologicalevidence
Measurablereductiontumour
§ Humanevidence
Ethical/Robust/Statisticallysound
§ Humanproof
Cell lines
Xenografts
Cell lines
Xenograft models
NewandEffectiveTherapies
Howdoknowifatherapyisgoingtokillbreast
cancercells?
Molecularlevel
§ Biologicalplausibility
ProofinCelllines/Xenografts
§ Biologicalevidence
Measurablereductiontumour
§ Humanevidence
Ethical/Robust/Statisticallysound
§ Humanproof
NewandEffectiveTherapies
Howdoknowifatherapyisgoingtokillbreast
cancercells?
Molecularlevel
§ Biologicalplausibility
ProofinCelllines/Xenografts
§ Biologicalevidence
Measurablereductiontumour
§ Humanevidence
Ethical/Robust/Statisticallysound
§ Humanproof
ClinicalTrial– Hallmarksofproof
ETHICAL
Soundscientificbackground– alreadydiscussed
Independent ethicalreview– scientists,consumer,lawyer,
otherhealthprofessionals
Patientinformedconsent: Background,Hope,Risks,
ROBUST
Patientfitness
Tumourcharacteristics
Pre-defined
Same between groups
Entryassessmentoftumour
Statistically sound– minimisechanceeffect
Conductoftrialuniform
Resultsmeasured&monitored
Independentoverview
Results tobeanalysedarepre-determined
Resultsarepeerreviewed
Resultsarehealth authorityreviewed
Tamoxifen, Fulvestrant
Estrogen receptor
Anastrozole, Letrozole, Exemestane
Single Tyrosine kinase inhibitors: Gefitinib, Erlotonib
EGFR family
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Trastuzumab, T-DM1, Pertuzumab
Lapatinib, Neratinib, EKB-569, BIBW2992
VEGF / VEGFR
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Bevacizumab, Aflibercet
Sunitinib, Sorafenib, Axitinib, Motasenib, Cedirinib, Vandetanib, Vatalanib
RAS / MEK / ERK
Tipifarnib
mTOR
Everolimus, Temsirolimus, Deforolimus
PI3K/AKT
Buparlisib, Alpelisib
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IGFR
CP-751,856; AMG479, IMC-A12
PARP
Olaparib, Veliparib, AGO14699
CDK 4/6
Palbociclib, Ribociclib, Abemaciclib
PD1, PD-L1
Pembrolizumab, Atezolizumab
Other Immune targets
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MCS110, Talimogene Laherparepvec
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• NewandEffectiveTherapies
• Safecomplementarytherapiesvsunprovenalternatives
• Howcanwereachthewiderbreastcancercommunity–
gettingtherightinformation.
• Whataspectsofcarecouldbeimprovedforadvanced
breastcancerpatients?
∼ Hallmarksofcomplementarytherapies∼
§ Makenoclaimstokillingcancer/prolonginglife
§ Aimedatmakingyoufeelbetter
§ Aimedatassistingdigestivetract
§ Manyareexternal– reiki,acupuncture,music
therapy,hypnotherapy,massage,exercise
§ Advicetoimprovediet– “commonsense”
Hallmarksofunproventherapies
§ Biologicalplausibility
Molecularlevel
§ Biologicalevidence
ProofinCelllines/Xenografts
§ Humanevidence
Measurablereductiontumour
§ Humanproof
Ethical/Robust/Statisticallysound
Howcanwereachthewider
breastcancercommunity?
Gettingtherightinformation
∼ Gettingtherightinformation∼
§ Breastcancertumourmarker
§ Scans– whichones,risks
§ “Naturalhistory”ofmetastaticbreast
cancer
§ Forthefamily&friendsofapatient
Breastcancertumourmarker
§ Thisisaprotein:CA15-3,CA19-9
Breastcancertumourmarker
§ Thisisaprotein:CA15-3,CA19-9
§ Wheredoesitcomefrom?
• Shedfromsurfaceofbreastcancercell
• Morecommonlyfrombonemetastases
Breastcancertumourmarker
§ Thisisaprotein:CA15-3,CA19-9
§ Wheredoesitcomefrom?
§ Doesithaveafunction&isitdangerous?
Breastcancertumourmarker
§ Thisisaprotein:CA15-3,CA19-9
§ Wheredoesitcomefrom?
§ Doesithaveafunction&isitdangerous?
§ Doeseverybreastcancerpt haveone?
• RarelyelevatedinEarlybreastcancer
• 30%– 80%ofMetastaticbreastcancer
Breastcancertumourmarker
§ Thisisaprotein:CA15-3,CA19-9
§ Wheredoesitcomefrom?
§ Doesithaveafunction&isitdangerous?
§ Doeseverybreastcancerpt haveone?
§ Ifitisnotabnormal,whatdoesitmean?
• Ifnotpresent,itmeansnothingandisnotusefulfor
managementdecisionsinMBC
Breastcancertumourmarker
§ Thisisaprotein:CA15-3,CA19-9
§ Wheredoesitcomefrom?
§ Doesithaveafunction&isitdangerous?
§ Doeseverybreastcancerpt haveone?
§ Ifitisnotabnormal,whatdoesitmean?
§ Ifitiselevated,whatdoesitmean?
• ItcanASSISTmanagementinMBConly,notEarly
Breastcancertumourmarker
§ Thisisaprotein:CA15-3,CA19-9
§ Wheredoesitcomefrom?
§ Doesithaveafunction&isitdangerous?
§ Doeseverybreastcancerpt haveone?
§ Ifitisnotabnormal,whatdoesitmean?
§ Ifitiselevated,whatdoesitmean?
§ Whatelsewouldyouliketoknowaboutit?
Scans– Whichones,Risksvs.Benefit
§ Principle:
• Needtoknowobjectivelythattumour isrespondingto
treatment
• Long-termriskofradiationexposure,BUT,nevershown
tobedetrimentalincaringforMBCpts
X-Rays
Ultrasound
CT scan
MRI scan
Bone scan
PET scan
Scans– whichones
§ Dependsonwhatinformationisbeingsought
§ Beguidedbyyourdoctor
§ Toooftenmaynotbenecessary
§ Toolongapartmaynotconfirmthattreatmentis
workingornot
Scans– whichones
§ Somesitesofbreastcancersecondariesaredifficult
tofollowwithoutscans
• E.g.Lungs,Lungsurface(pleura),Lymphnodeswihtin
thechestcavity
• Insideabdominalcavity
§ Somesitesaredifficulttointerpretandsequential
scansareneeded
• E.g.Bones
“Naturalhistory”ofmetastaticbreastcancer
Factorsthatdictatetrajectoryforagivenpatient
§ Typeofbreastcancer
Determines:
Timetotreatmentresistance
Tumourgrowthdevolution
§ Volumeofbreastcancer
§ Braininvolved
§ Timesince&treatmentreceivedforearlyBC
§ Overallorganhealth
§ Recommendedtreatment
“Naturalhistory”ofmetastaticbreastcancer
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Explains variability of what happens for a given patient
You can determine
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ForFamily&Friends
Whatdoyouwantforyourlovedonewhohasbreast
cancer?
• Wantthemtobecured
• Wantthemtohavethebesttreatment
• Wantthemtobeliketheir“old”self
• Nopainorsymptoms
• Livinglifeastheyusedto
• Wanttoprotectchildren/sibling/parent
ForFamily&Friends
Whatcanyoudo?
§ Practical,Practical,Practical
§ Financial
§ Supportyourlovedone’sdecisionwithgentle“wisdom”
§ Knowthestatusofthediseaseandtreatment
Whatyoushouldn’tdo
§ Don’tgiveadviceaboutwhattreatmentthey
shouldhave
§ Don’tshareanotherpatient’sexperience
§ Don’ttellthemhowtheyshouldlive
Whataspectsofcarecouldbe
improvedforadvancedbreastcancer
patientsrightnowin2017?
∼ Aspectsofcarethatcanbeimproved∼
§ Drugtherapy
• Morepredictablyeffective
• Lesstoxic
• Moreaccessible
• Lessexpensive
∼ Aspectsofcarethatcanbeimproved∼
§ Diagnoseasearlyaspossiblei.e.1st signsofsymptoms
§ Offerthebestpossibletreatment
• Clinicaltrialifappropriate
• Optimalstandardofcareandfollow-up
§ Preventincorrect&unproventherapiesbeingused
§ Identify&helpaddressissuesimportanttoBrC patient
• Children,Spouse/Partner
• Financial/Employmentaspects
§ ImprovecommunityunderstandingofMBC
UpdateonBCRC-WAactivities
§ Workingtoestablishabreastcancercomprehensive
cancercentre
§ Designpatientfocusedresearch
• Childrenofbreastcancerpatients
• ImportanceofImmunecellsinthecommonesttypeof
breastcancer(Estrogen+)
§ OngoingstudiesofbiologyofBrC
§ Ongoingdrugtrials
§ Education:Residents,Oncologists,GPs,AlliedHealth,
Community
§ InauguralBCRC-WABreastOncologyFellowship
§ PYNKS– joinourgroup&makeitusefultoyou
§ BeaFriendofBCRC-WA
• Getourbimonthlynewsletter
• Helpustodoworthwhileresearch&education–
donations,yourexpertise
• Bepartofthesolution