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I have a BRCA1/2 gene mutat ion Everything you need to know about BRCA1/2 gene mutat ions (NHS England 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%

10-20%

Breastcancerinwomen

11% 60-85% 45-60%

BreastCancerinmen 0.1%

Upto3%

Upto12%

Prostatecancer 12% Elevatedrisk(%unknown)

35-40%

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

ScreeningTheNationalBreastScreeningProgrammeoffers50-70yearoldwomenmammogramseverythreeyearsontheNHS.Thereiscurrentlynonationalscreeningprogrammeforovariancancer.SurveillanceWomenwithaBRCA1/2genemutationareofferedyearlyMRIscans,fromtheageof30,tocheckforbreastcancer.Surveillanceisn’troutinelyofferedforovariancancerbutitmaybepossibletohaveregularCA125bloodtestsandpelvicultrasoundscans.TalktoyourGPtofindoutwhatisavailablelocally.SurgeryYoumayhavetheoptionofhavingsurgerytoremoveyourovariesand

fallopiantubes,whichwillreducetheriskofcancerdeveloping.Aswellasreducingyourriskofdevelopingbreastcancerby50%,havingyourovariesandfallopiantubesremoved(bilateralsalpingo-oophorectomy)willreduceyourriskofdevelopingovariancancerto5%.

Thissurgerymaybeofferedinadditiontoarisk-reducingmastectomy,whichwillreduceyourbreastcancerriskfurther;to5-10%.Anotheroptionyoumaybegivenistohavearisk-reducingsalpingectomy(removingthefallopiantubesonly);asevidencesuggeststhatthemajorityofBRCA1/2-associatedcancersstartattheendofthefallopiantube.However,whileevidencefromthegeneralpopulationsuggeststhatremovingtubesapproximatelyhalvesriskofovariancancer,thereisnocurrentevidenceofsafetyorefficacyofthisapproachinwomenwithBRCA1/2genemutations.Infact,currentresearchsuggeststhatitofferslessprotectionthanremovingtheovariestoo.

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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.

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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

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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%.

AccordingtoNHSEngland’sclinicalcommissioningpolicy‘Pre-implantationGeneticDiagnosis’uptothreecyclesareavailableontheNHSintheUK,butonlyoneunaffectedchildwillbefunded.ReferralsforPGDwillneedtogothroughthegeneticsserviceso,ifyouwouldliketoconsiderthisprocedure,speaktoyourgeneticsspecialist.Formoreinformation,seewww.geneticalliance.org.uk/aboutpgd.htmPre-nataltestingEarlyoninapregnancyitispossibletotestforinheritedgeneticmutations.Youwillthenhaveachoicewhethertocarryonwiththepregnancyorterminateitearly.Thisisaninvasiveprocedurewithaslightriskofmiscarriage.Formoreinformationaboutpre-nataltestingandtheoptionsavailabletoyou,youcanspeaktoyourgeneticsspecialist,gynaecologistorGP.EggorspermdonationDependingonwhetherit’sthefuturemotherorfatherthathasthemutationtheneggorspermdonationcanbeconsideredtoavoidpassingonthegeneticmutation.Ifthemotheristhecarrierofthemutation,eggscanbedonatedandifthefatheristhecarrier,spermcanbedonated.Oncedonated,IVFcanbecarriedout.

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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.GiventhatthecancersattributedtotheBRCA1/2genemutationsdon’tusuallyariseuntilpeopleareintheir20sor30s(orlater),thetestingofyoungchildrenisnotusuallyavailable,asactioncan’tbetakenuntiltheyareover18.Itisalsogenerallybetterifchildrencanbeinvolvedindiscussionsabouttheirowngenetictesting,and

thisisnotpossibleforveryyoungchildren.Teenagersmaybenefitfromadiscussionwithageneticsteam,eveniftestingisnotcarriedoutuntiltheyare18.TellingyourextendedfamilyYourgeneticsteamwillhelpyouidentifywhichofyourextendedfamilymayalsohaveinheritedthemutation.Thiswilldependonwhatsideofthefamily–yourfather’sormother’s–thegenewaspasseddownfrom.Oncethisisestablished,yourbrothers,sisters,aunts,unclesandcousinsonthatsideofthefamilywillbeknowntobeatriskofhavinginheritedthemutation.Whileitisrecommendedthattheyareinformed,therearecurrentlynoofficialprocedurestoassistwiththisandtheresponsibilityanddecisiontotellthemlieswithyou.Ifyoudon’tfeelcomfortablehavingthisdiscussionwithyourfamilymembers,yourgeneticscliniccanhelpwiththis.Forexample,theymaybeabletogiveyouinformationtopasson.Thiswillexplainthatafamilymemberhasaninheritedgeneticmutationandwilldescribewhatthismightmeantothemandhowtheycanobtainareferraltotheirnearestgeneticsclinicforgeneticcounsellingandtesting.

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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,2013ClinicalCommissioningPolicy:GeneticTestingforBRCA1andBRCA2Mutations,NHSEngland,2015Ovariancancer:recognitionandinitialmanagement,NICE,2011Familialbreastcancer:classification,careandmanagingbreastcancerrelatedrisksinpeoplewithafamilyhistoryofbreastcancer,NICE,2013AdditionalcontentsuppliedbyClinicalGeneticsdepartmentatGreatOrmondStreetHospital.January2016AdditionalcontentgatheredfromOvarianCancerAction’sactingonBRCAevent.November2015.http://ovarian.org.uk/news-and-campaigning/blog/brca-lecture-right-to-know-impact-on-familyAdditionalcontentsuppliedbyLeelaBarham,IndependentHealthEconomist.October2015.NHSEnglandClinicalCommissioningPolicy:Pre-implantationGeneticDiagnosis(PGD),April2013.https://www.england.nhs.uk/wp-content/uploads/2013/04/e01-p-a.pdf

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