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I have a BRCA1/2 gene mutat ion Everything you need to know about BRCA1/2 gene mutat ions (Scot land only)

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What having a BRCA1/2 gene mutat ion means ReceivingapositivetestresultforaBRCA1/2genemutationcanbefrighteningbuttherearestepsyoucantaketomakeitlessdaunting.Thisguideaimstohelpyoufeelarmedwithalltheinformationyouneed.Apositivetestmeansthatyourchanceofdevelopingcertaincancerswillbe

higherthansomeonewhodoesnothaveageneticmutationinthesegenes.ThistableexplainshowyourriskincreasesaccordingtowhetheryouhaveaBRCA1oraBRCA2genemutation.

EstimatedCancerRiskbyAge70

TypeofCancer Normalrisk BRCA1Risk BRCA2RiskOvariancancer

2% 40-60%

10-30%

Breastcancerinwomen

11% 60-90% 45-85%

BreastCancerinmen 0.1%

0.1-1%

5-10%

Prostatecancer 12% Elevatedrisk(%unknown)

20-25%

Pancreaticcancer 1.3% 3-4% 7%

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ChanceofpassingmutationsonWhetheryou’reamotherorafather,ifyouhaveamutationineitherBRCA1/2genethenthereisa50%chanceofpassingthemutationontoyourchildren.ThereareafewpossibleoutcomesifbothparentscarryaBRCA1/2genemutation:

• Thereisa1in2chancethatyourchildwillinheritasingleBRCA1/2genemutationanda1in4chancethatyourchildwillnotinheritanyBRCA1/2genemutationatall.Thereisalsoa1in4chancethattheywillinheritbothofthemutations.

• Ifoneparenthasamutationintheir

BRCA1geneandtheotherintheirBRCA2geneandthechildinheritsboth,thentheirriskofdevelopingbreastorovariancanceristhatofaBRCA1carrier.

• IfachildinheritstheBRCA2genemutationfrombothsides,thentheywillhavesomethingcalledfanconianaemia(alsoknownasfanconisyndrome).Thisdisordercanleadtoshortergrowth,asmallerheadandunderdevelopedthumbs.Fanconianaemiaalsoputsthechildathigherriskofearlychildhoodcancers,leukaemiaandwilmstumoursinthekidneys.

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What act ion can I take? LifestyleWhilethesewon’tstopyoufromdevelopingovariancancer,thereareanumberoflifestylerelatedfactorsthatcanhelploweryourrisk.Theseinclude:

• Usingtheoralcontraceptivepill• Breastfeeding,ifyouhavetheoption• Maintainingahealthyweight• Eatingahealthy,balanceddiet• Exercisingregularly• Notsmoking

ScreeningandsurveillanceScreeningThereiscurrentlynonationalscreeningprogrammeforovariancancer.ScottishIntercollegiateGuidelinesNetwork(SIGN)statedthatscreeningforovariancancerinhighriskgroupsshouldonlybeofferedinthecontextofaresearchstudy.ScottishBreastScreeningProgramme(SBSP)screensallwomenforbreastcancerbetweentheagesof50and70.SurveillanceIfyoucarryaBRCA1/2mutationoryouareatincreasedriskofdevelopingbreastcancerandyouareyounger,youwillbeofferedeitheranannualmammogramorMRIscandependingonyourageandlevelofrisk.WithaBRCA1/2mutation,surveillanceisofferedfrom30yearsold.

SurgeryYoumayhavetheoptionofhavingsurgerytoremoveyourovariesandfallopiantubes,whichwillreducetheriskofcancerdeveloping.Aswellasreducingyourriskofdevelopingbreastcancerby50%,havingyourovariesandfallopiantubesremoved(bilateralsalpingo-oophorectomy)willreduceyourriskofdevelopingovariancancerto5%.Thissurgerymaybeofferedinadditiontoarisk-reducingmastectomy,whichwillreduceyourbreastcancerriskfurther;to5-10%.SIGNguidelinesstatethatprophylacticsalpingo-oophorectomyandremovaloffallopiantubesshouldbeofferedtowomenwithgeneticmutationsofBRCA1orBRCA2genesatarelevanttimeoftheirlife.Womenathighriskinwhommutationshavenotbeenidentifiedshouldhavetheopportunitytodiscusstheadvantagesanddisadvantagesofprophylacticsalpingo-oophorectomy.Womenwhodecidetohaveprophylacticsalpingo-oophorectomyshouldbeofferedcounselling,supportandinformationbeforeandaftersurgery.SIGNdoesnotrecommendremovingthefallopiantubeswithoutremovingtheovariesasthereisalackofevidencethatthisadequatelypreventsovariancancer.

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WhenshouldIhavesurgery?Ifyoudodecidetohavesurgery,youwillneedtoconsiderwhenthebesttimeisforyoutodoso.AgeisthebiggestfactorandthebelowgraphslookathowovariancancerriskchangeswithageinwomenwithaBRCA1/2genemutation.

GraphsadaptedfromAntoniouetal.AJHG2003 Inbothcases,thegraphsshownosignificantincreasedriskofovariancanceruntilage45.IfyouhaveaBRCA1genemutation,riskincreasesatage45-49andagainatage55-59.Therefore,surgeryisadvisedbyage40.RiskincreaseslaterifyouhaveaBRCA2genemutation,sosurgerycanbeleftuntilyouareinyourmid-40s.Youwillalsoneedtoconsidertheageyourrelativesdevelopedovarianorbreastcancerand,becauseriskreducingbilateralsalpingo-oophorectomywillmakeyouinfertile,whetherornotyou’vecompletedyourfamily.Youcandiscussallofthesefactorswithyourgeneticscounsellorbeforemakingafinaldecision.SIGNguidancestatesthattheoptimaltimingforsurgeryisbetweentheagesof35-40yearsandafterchildbearingiscomplete.

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What wi l l happen to me i f I have surgery?MedicalmenopauseThemostsignificantside-effectofriskreducingbilateralsalpingo-oophorectomyisthemenopause;thetimeinawoman’slifewhenshestopshavingperiods.Thenaturalmenopauseisusuallyverygradual,givingawomantimetoadjusttothechangesthatarehappeningtoherbody.Butwhenthemenopauseoccursbecausetheovariesaresurgicallyremoved,symptomscanbequitesevereduetotheabruptonsetofhormonalchanges.Symptomscaninclude:

• Hotflushes• Vaginaldiscomfortanddryness• Needingtoweemorefrequentlyand

urgently

Lesscommonsymptomsincludingbrittlenails,thinningoftheskin,hairlossandachesandpains

Besidesthephysicalsymptomsyoumayfeel:

• Tooyoungtobegoingthroughthemenopause

• Worriedaboutyouroptionstohaveababy

• Lessfeminine• Worriedaboutthefuture

TherearemanydifferentwaystotreatsymptomsofasurgicalmenopauseandyoumayliketodiscusstheoptionswithyourGPorconsultant:

• Followingahealthylifestyle• Hormonereplacementtherapy(HRT)• Anti-depressantssuchasCitalopram,

ParoxetineandVenlafaxine• Cognitivebehaviouraltherapy• Counselling• Herbalsupplements• Vaginaloestrogen

SIGNnotesthathormonereplacementcanbeusedafteroopherectomyuntilthetimeofnaturalmenopausewithoutlosingthebenefitsofbreastcancerriskreduction.

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Start ing a fami lyIfyouwanttostartafamily,butareworriedaboutpassingonageneticmutation,thereareafewoptionsyoucanexplore.Besidesadoption,theseinclude:HavingyourchildrenasnormalAparentwithaBRCA1/2genemutationhasa50%chanceofpassingitontotheirchildbutyoucan,ofcourse,haveyourchildrenasnormal.It’spossiblethattherewillbebetterscreeningandtreatmentofovariancanceroverthenextfewdecadesandanychildborntodaywillnotbeatriskofcancerformanyyears.Pre-implantationgeneticdiagnosis(PGD)Thisisaprocedurethataimstoallowfamiliestoavoidpassingonaninheritedconditiontotheirchildren.Itisonlyavailabletoparentswhohaven’talreadyconceivednaturally.Forthisprocedureyouwillhavetoundergoinvitrofertilisation(IVF).Thisinvolvescollectingyoureggsandfertilisingthemwithyourpartner’ssperminalaboratory.Cellsfromyourfertilisedeggs(embryos)arethentestedforagenemutation.Anembryothatdoesnothavethegenemutationisthentransferredtoyourwombandthenyourpregnancyisallowedtocontinueasnormal.Anyremaining,non-mutatedembryoscanbefrozenforuseinfuturecycles.ThesuccessrateforPGDisaround20%.

In2011,guidanceonPGDinScotlandstatedcouplesshouldbeabletoaccesstwoIVFcycleswithPGD,shouldtheymeetadditionalcriteria,including

previouslyhavingnotutilisedtwocyclesofNHSfundedPGDorIVF,ageofreferral(before39years)andbodymassindex(BMI)ofbetween19and35.IfyouareseekingareferralforPGD,thisistypicallythroughtheRegionalGeneticsServicewhereyouwillhavereceivedcounsellingandtestingforBRCAmutations.OnceyouhavestartedyourfirstcycleofIVF,youshouldnothavetoreturntothewaitinglisttobeabletoaccessthesecondcycleifrequired.Pre-nataltestingEarlyoninapregnancyitispossibletotestforinheritedgeneticmutations.Youwillthenhaveachoicewhethertocarryonwiththepregnancyorterminateitearly.Thisisaninvasiveprocedurewithaslightriskofmiscarriage.Formoreinformationaboutpre-nataltestingandtheoptionsavailabletoyou,youcanspeaktoyourgeneticsspecialist,gynaecologistorGP.EggorspermdonationDependingonwhetherit’sthefuturemotherorfatherthathasthemutationtheneggorspermdonationcanbeconsideredtoavoidpassingonthegeneticmutation.Ifthemotheristhecarrierofthemutation,eggscanbedonatedandifthefatheristhecarrier,spermcanbedonated.Oncedonated,IVFcanbecarriedout.Formoreinformationabouteggorspermdonationandtheoptionsavailabletoyou,youcanspeaktoyourgeneticsspecialist,gynaecologistorGP.

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Tel l ing your fami lyTellingyourfamilythatyouhaveaBRCA1/2genemutationmayseemdaunting.Justrememberthatyoudohaveoptions,andthereissupportavailable.Tellingyourchildren1.Youcandelaytellingyourchildrenuntilyoufeeltheyareoldenough.Thebenefitofthisisthatitdoesn’tcausethemanydistressatanagewhenyoumayfeelitistoomuchforthemtohandleorunderstand.2.Youcantellthematayoungage.Thebenefitofthisisthattheyhavetimetocometotermswiththeirpossibleriskandyoucanstarthavingdiscussionsearlyonaboutsomeofthedifficultdecisionstheymayhavetomake.Thereisnorightorwrongtimetotellyourchildren.You’llwanttodiscussthiswithsomeoneclosetoyou,andwithyourgeneticsteam,tohelpyoutodecidewhichwouldbethebestoptionforyourfamily.

TellingyourextendedfamilyYourgeneticsteamwillhelpyouidentifywhichofyourextendedfamilymayalsohaveinheritedthemutation.Thiswilldependonwhatsideofthefamily–yourfather’sormother’s–thegenewaspasseddownfrom.Oncethisisestablished,yourbrothers,sisters,aunts,unclesandcousinsonthatsideofthefamilywillbeknowntobeatriskofhavinginheritedthemutation.Whileitisrecommendedthattheyareinformed,therearecurrentlynoofficialprocedurestoassistwiththisandtheresponsibilityanddecisiontotellthemlieswithyou.Ifyoudon’tfeelcomfortablehavingthisdiscussionwithyourfamilymembers,yourgeneticscliniccanhelpwiththis.Forexample,theymaybeabletogiveyouinformationtopasson.ThiswillexplainthatafamilymemberhasaninheritedgeneticmutationandwilldescribewhatthismightmeantothemandhowtheycanobtainareferraltoRegionalGeneticsUnitforgeneticcounsellingandtesting.

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The real impact of BRCA1/2

test ing: The pat ient v iew

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References & resources

ABeginnersGuidetoBRCA1andBRCA2,TheRoyalMarsdenNHSFoundationTrust,2013SIGN135ManagementofepithelialovariancancerAnationalclinicalguidelineNovember2013.Fullguidelineandquickreferenceguide:http://www.sign.ac.uk/guidelines/fulltext/135/index.htmlGuidancetosupporttheImplementationofGeneticsServicesforBreast,OvarianandColorectalCancerPredispositionScottishCancerGroupCancerGeneticsSub-group.CancerGeneticsServicesinScotlandMarch2001:http://www.show.scot.nhs.uk/sehd/mels/HDL2001_24Guide.pdfTheScottishPre-ImplantationGeneticDiagnosisandScreeningServiceApril2011AFrameworkforDecisionMakingfortheScottishPGDService.Availableathttp://www.nsd.scot.nhs.uk/documents/pgdframework.pdfSPICeBriefingGeneticHealthcare&PublicHealthScreeninginScotlandGaryWKerrTheScottishParliament2012.Availableathttp://www.scottish.parliament.uk/ResearchBriefingsAndFactsheets/S4/SB_12-55.pdfAdditionalcontentgatheredfromOvarianCancerAction’sactingonBRCAevent.November2015.http://ovarian.org.uk/news-and-campaigning/blog/brca-lecture-right-to-know-impact-on-familyAdditionalcontentsuppliedbyClinicalGeneticsdepartmentatGreatOrmondStreetHospital.January2016AdditionalcontentsuppliedbydoctorspractisinginEastandWestScotland.April2016AdditionalcontentsuppliedbyCancerGeneticsdepartmentatNHSGreaterGlasgow&Clyde.August2016AdditionalcontentsuppliedbyLeelaBarham,IndependentHealthEconomist.October2015.

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ForfurtherinformationaboutBRCA1/2genetictestingandtheotherworkundertakenbyOvarianCancerAction,pleasecontactRossLittleat:OvarianCancerAction8-12CamdenHighStreetLondonNW10JHross@ovarian.org.ukwww.ovarian.org.uk02073801730