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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 * * ** ** Trastuzumab, T-DM1, Pertuzumab Lapatinib, Neratinib, EKB-569, BIBW2992 VEGF / VEGFR * Bevacizumab, Aflibercet Sunitinib, Sorafenib, Axitinib, Motasenib, Cedirinib, Vandetanib, Vatalanib RAS / MEK / ERK Tipifarnib mTOR Everolimus, Temsirolimus, Deforolimus PI3K/AKT Buparlisib, Alpelisib ** 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 ** MCS110, Talimogene Laherparepvec ** ** ** * • 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 # # # # # * * * * * Explains variability of what happens for a given patient You can determine * 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