You are on page 1of 15

Thissiteisintendedforhealthcareprofessionals

OvarianCancer
Updated:Aug24,2016
Author:AndrewEGreen,MDChiefEditor:fromMemorialSloanKetteringYukioSonoda,MD
more...

OVERVIEW

PracticeEssentials
OvariancanceristhemostcommoncauseofcancerdeathfromgynecologictumorsintheUnited
States.Malignantovarianlesionsincludeprimarylesionsarisingfromnormalstructureswithinthe
ovaryandsecondarylesionsfromcancersarisingelsewhereinthebody.Primarylesionsinclude
epithelialovariancarcinoma(70%ofallovarianmalignancies).Currentresearchsuggeststhatthe
majorityoftheseoriginatefromthefallopiantubes.
Stromaltumorsoftheovaryincludegermcelltumors,sexcordstromaltumors,andothermorerare
types.Metastasestotheovariesarerelativelyfrequentcommonsourcesaretumorsinthe
endometrium,breast,colon,stomach,andcervix.Seetheimagebelow.

Anenlargedovarywithapapillaryserouscarcinomaonthesurface.

ViewMediaGallery

Signsandsymptoms
Earlyovariancancercausesminimal,nonspecific,ornosymptoms.Thepatientmayfeelan
abdominalmass.Mostcasesarediagnosedinanadvancedstage.
Epithelialovariancancerpresentswithawidevarietyofvagueandnonspecificsymptoms,including
thefollowing:

Bloatingabdominaldistentionordiscomfort
Pressureeffectsonthebladderandrectum
Constipation
Vaginalbleeding
Indigestionandacidreflux
Shortnessofbreath
Tiredness
Weightloss
Earlysatiety
Symptomsindependentlyassociatedwiththepresenceofovariancancerincludepelvicand
abdominalpain,increasedabdominalsizeandbloating,anddifficultyeatingorfeelingfull.[1]
Symptomsassociatedwithlaterstagediseaseincludegastrointestinalsymptomssuchasnauseaand
vomiting,constipation,anddiarrhea.[2]Presentationwithswellingofalegduetovenousthrombosis
isnotuncommon.Paraneoplasticsyndromesduetotumormediatedfactorsleadtovarious
presentations.
SeeClinicalPresentationformoredetail.

Diagnosis
Physicalfindingsareuncommoninpatientswithearlydisease.Patientswithmoreadvanceddisease
maypresentwithovarianorpelvicmass,ascites,pleuraleffusion,orabdominalmassorbowel
obstruction.
Thepresenceofadvancedovariancancerisoftensuspectedonclinicalgrounds,butitcanbe
confirmedonlypathologicallybyremovaloftheovariesor,whenthediseaseisadvanced,by
samplingtissueorasciticfluid.
Screening
TheUSPreventiveServicesTaskForce(USPSTF)recommendsagainstscreening(withserum
CA125levelortransvaginalultrasonography)forovariancancerinthegeneralpopulation.[3]The
NationalCancerInstitute(NCI)recommendsthathighriskwomenseekadvicefromtheirphysicians
andconsiderhavingannualultrasonographicexaminationsandannualCA125testing,aswellas
consideroophorectomyorparticipationinaclinicaltrial.
Laboratorytesting
Notumormarker(eg,CA125,betahumanchorionicgonadotropin,alphafetoprotein,lactate
dehydrogenase)iscompletelyspecifictherefore,usediagnosticimmunohistochemistrytestingin
conjunctionwithmorphologicandclinicalfindings.Also,obtainaurinalysistoexcludeotherpossible
causesofabdominal/pelvicpain,suchasurinarytractinfectionsorkidneystones.
Imagingstudies
Routineimagingisnotrequiredinallpatientsinwhomovariancancerishighlysuggested.Incasesin
whichthediagnosisisuncertain,considerthefollowingimagingstudies:
Pelvicultrasonography[4,5]:Warranted
Pelvicandabdominalcomputedtomography(CT)scanning[4,5]:Warranted
Pelvicandabdominalmagneticresonanceimaging:Increasesspecificityofimagingwhen
sonographyfindingsareindeterminate[6]

Chestradiography:Routineimagingtoexcludelungmetastases
Mammography:Partofpreoperativeworkupforwomenolderthan40yearswhohavenothad
oneinthepreceding612monthsestrogenproducingtumorsmayincreasetheriskofbreast
malignancies,andbreastcancerscanmetastasizetotheovariesandareoftenbilateral
InpatientswithdiffusecarcinomatosisandGIsymptoms,aGItractworkupmaybeindicated,
includingoneofthefollowingimagingstudies:
Upperand/orlowerendoscopy
Bariumenema
UpperGIseries
Procedures
Fineneedleaspiration(FNA)orpercutaneousbiopsyofanadnexalmassisnotroutinely
recommended,asitmaydelaydiagnosisandtreatmentofovariancancer.Instead,ifaclinical
suggestionofovariancancerispresent,thepatientshouldundergolaparoscopicevaluationor
laparotomy,basedonthepresentation,fordiagnosisandstaging.AnFNAordiagnosticparacentesis
shouldbeperformedinpatientswithdiffusecarcinomatosisorasciteswithoutanobviousovarian
mass.
SeeWorkupformoredetail.

Management
Standardtreatmentforwomenwithovariancancerinvolvesaggressivedebulkingsurgeryand
chemotherapy.Theaimofcytoreductivesurgeryistoconfirmthediagnosis,definetheextentof
disease,andresectallvisibletumor.Neoadjuvantchemotherapyisincreasinglyused.
Surgery
Thetypeofproceduredependsonwhetherornotdiseaseisvisibleoutsidetheovaries.Whenno
diseaseisvisibleoutsidetheovaries,ornolesiongreaterthan2cmispresentoutsideofthepelvis,
thepatientrequiresformalsurgicalstaging,includingperitonealcytology,multipleperitonealbiopsies,
omentectomy,pelvicandparaaorticlymphnodesampling,andbiopsiesofthediaphragmatic
peritoneum.
Ifdiseasegreaterthan2cmisnotedthenaggressivesurgicaldebulking,withtheintenttoremoveall
visiblediseaesshouldbeundertaken.Ifthesurgeondeterminesthatoptimaldebulkingisnot
possible,thenneoadjuvantchemotherapyshouldbeconsidered.ForpatientswithstageIVdisease,
surgeryshouldbeindividualizedonthebasisofpresentation.
Surgicalproceduresthatmaybeperformedinwomenwithovariancancerareasfollows:
Surgicalstaging
Cytoreductivesurgery
Intervaldebulking
Laparoscopicsurgery
Secondarysurgery
Chemotherapy
Postoperativechemotherapyisindicatedinallpatientswithovariancancer,exceptthosewhohave
surgicalpathologicstageIdiseasewithlowriskcharacteristics.Standardpostoperative

chemotherapyforovariancanceriscombinationtherapywithaplatinumcompoundandataxane(eg,
carboplatinandpaclitaxel).Additionalagentsforrecurrentdiseaseincludethefollowing:
Liposomaldoxorubicin
Etoposide
Topotecan
Gemcitabine
Vinorelbine
Ifosfamide
Fluorouracil
Melphalan
Altretamine
Bevacizumab
Olaparib
Adjunctivemedicationsincludethefollowing:
Cytoprotectiveagents(eg,mesna)
Antiemetics(eg,ondansetron,granisetron,palonosetron,dexamethasone)
SeeTreatmentandMedicationformoredetail.

Background
Malignantlesionsoftheovariesincludeprimarylesionsarisingfromnormalstructureswithintheovary
andsecondarylesionsfromcancersarisingelsewhereinthebody.Primarylesionsincludeepithelial
ovariancarcinoma(70%ofallovarianmalignancies),germcelltumors,sexcordstromaltumors,and
othermoreraretypes.Metastasestotheovariesarerelativelyfrequent,withthemostcommonbeing
fromtheendometrium,breast,colon,stomach,andcervix.
Althoughmanyhistologictypesofovariantumorshavebeendescribed,morethan90%ofovarian
malignanciesareepithelialtumors.Manyoftheseactuallyoriginateinthefallopiantubes.(See
Pathophysiology.)
Theprecisecauseofovariancancerisunknown.However,severalriskandcontributingfactors
(includingbothreproductiveandgeneticfactors)havebeenidentified.(SeeEtiology.)
OvariancanceristhemostcommoncauseofcancerdeathfromgynecologictumorsintheUnited
States.Aroundtheworld,morethan200,000womenareestimatedtodevelopovariancancerevery
yearandabout100,000diefromthedisease.Thelifetimeriskofawomandevelopingepithelial
ovariancanceris1in70.(SeeEpidemiology.)
Earlydiseasecausesminimal,nonspecific,ornosymptoms.Therefore,mostcasesarediagnosedin
anadvancedstage.Prognosisinovariancanceriscloselyrelatedtothestageatdiagnosisthus,
overall,prognosisforthesepatientsremainspoor.(SeePresentationandPrognosis.)
Standardtreatmentinvolvesaggressivedebulkingsurgeryfollowedbychemotherapy.The
incorporationofneoadjuvantchemotherapyhasrecentlyincreased,withmultiplestudiesindicating
thatinsomesituationsitoffersanimprovementinmorbidityandpossiblysurvival.(SeeTreatmentand
Medication.)

Pathophysiology

Historically,mosttheoriesofthepathophysiologyofovariancancerincludedtheconceptthatitbegins
withthededifferentiationofthecellsoverlyingtheovary.Duringovulation,thesecellscanbe
incorporatedintotheovary,wheretheythenproliferate.However,newevidenceindicatesthatthe
majorityofthesetumorsactuallyoriginateinthefimbriaofthefallopiantube.Detailedpathologic
studieshavepushedmuchofthethinkingabouttheoriginofthesetumorsinthisdirection.[7]
Ovariancancertypicallyspreadstotheperitonealsurfacesandomentum.Spreadcanoccurbylocal
extension,lymphaticinvasion,intraperitonealimplantation,hematogenousdissemination,or
transdiaphragmaticpassage.Intraperitonealdisseminationisthemostcommonandrecognized
characteristicofovariancancer.Malignantcellscanimplantanywhereintheperitonealcavitybutare
morelikelytoimplantinsitesofstasisalongtheperitonealfluidcirculation.
Thesemechanismsofdisseminationrepresenttherationaletoconductsurgicalstaging,debulking
surgery,andintraperitonealadministrationofchemotherapy.Incontrast,hematogenousspreadis
clinicallyunusualearlyoninthediseaseprocess,althoughitisnotinfrequentinpatientswith
advanceddisease.
Epithelialtumorsrepresentthemostcommonhistology(90%)ofovariantumors.Otherhistologies
includethefollowing:
Sexcordstromaltumors
Germcelltumors
Primaryperitonealcarcinoma
Metastatictumorsoftheovary

Epithelialovariancancer
Epithelialovariancanceristhoughttoarisefromepitheliumcoveringthefimbriaofthefallopiantubes,
ortheovaries,bothofwhicharederivedfromthecoelomicepitheliuminfetaldevelopment.This
coelomicepitheliumisalsoinvolvedinformationofthemllerianducts,fromwhichthefallopiantubes,
uterus,cervix,anduppervaginadevelop.
Fourmainhistologicsubtypes,whicharesimilartocarcinoma,ariseintheepithelialliningofthe
cervix,uterus,andfallopiantube,asfollows:
Serous(fromfallopiantube)
Endometrioid(endometrium)
Mucinous(cervix)
Clearcell(mesonephros)
Somevariationisobservedinthepatternsofspreadanddiseasedistributionwithinthevarious
histologicsubtypes.
Epithelialtumorsarefoundaspartiallycysticlesionswithsolidcomponents.Thesurfacemaybe
smoothorcoveredinpapillaryprojections(seetheimagebelow),andthecystscontainfluidranging
fromstrawcoloredtoopaquebrownorhemorrhagic.

Anenlargedovarywithapapillaryserouscarcinomaonthesurface.

ViewMediaGallery
Epithelialovariancancermostoftenspreadsinitiallywithintheperitonealcavity(seetheimage
below).Metastaticdiseaseoftenisfoundontheperitonealsurfaces,particularlyontheundersurface
ofthediaphragms,theparacolicgutters,thebladder,andtheculdesac.Othercommonsitesareas
follows:
Surfaceoftheliver
Mesenteryandserosaofthelargeandsmallbowel
Omentum
Uterus
Paraaorticandpelviclymphnodes

Metastasesfromepithelialovariancarcinomainvolvingtheomentum.

ViewMediaGallery
Outsidetheperitonealcavity,epithelialovariancancermayspreadtothepleuralcavity,lungs,and
groinlymphnodes.Thepresenceofpleuraleffusiondoesnotnecessarilyindicatediseaseinthe
chest,andmalignancycanbediagnosedonlycytologically.Mucinoustumorstendtoformlarge

dominantmasses,whilepapillaryseroustumorshaveamorediffusedistributionandaremore
commonlybilateral.Endometrioidandclearcellvariantsmorecommonlyexhibitlocalinvasion,
retroperitonealdisease,andhepaticmetastases.
Increasingevidencesuggeststhatahighproportionofhighgradeserouscarcinomaoriginatesfrom
distalfallopiantubeepitheliumorthetuboperitonealjunctionratherthantheovariansurface
epithelium.Serousintraepithelialorearlyinvasivecarcinomahasbeenfoundinupto10%offallopian
tubesfromBRCAmutationcarrierswhohadundergoneprophylacticbilateralsalpingo
oophorectomies.Clinical,molecular,andgeneticstudies,aswellasinvitroandanimalmodels,have
alsosupportedatubaloriginforhighgradeserousovariancarcinoma.[7,8]
Thosefindingshavepromptedthesuggestionthatpreventionofovariancancerinselectedwomenat
highriskcouldbebetteraccomplishedwithsalpingectomy.Astudycomparingstandardriskreducing
salpingooophorectomywiththecombinationofearlyriskreducingsalpingectomyanddelayed
oophorectomyinBRCAcarriersiscurrentlyrecruitingparticipants.[9]
Tumorsoflowmalignantpotential
Tumorsoflowmalignantpotential(LMP),orborderlinetumors,areadistinctvarietyofepithelial
ovariancancerthatbehaveinamuchlessaggressivefashionandhaveaveryfavorableprognosis.
Thesetumorscausegreatanxietytopatients,andtheconceptofLMPsometimesisdifficultto
explain.Theycompriseapproximately20%ofmalignantovariantumors.Themeanageofdiagnosis
isyoungerthanforinvasiveepithelialovariancancer,atapproximately48years,andnolargepeakof
incidenceisobserved.
Thesetumorsarestagedidenticallytoepithelialovariancancer,usingtheFIGO(Fdration
InternationaledeGyncologieetd'ObsttriqueInternationalFederationofObstetricsand
Gynecology)system.Incontrasttoepithelialovariancancer,however,mostLMPtumorsarestageIat
presentation,withadistributionasfollows:
StageIA:51%
StageIB:6%
StageIC:18%
StagesIIIII:15%
StageIV:2%
LMPtumorscancausearangeofsymptomssimilartoepithelialovariancancer,includingincreasing
abdominalgirth,anabdominalmass,abdominalpain,abnormaluterinebleeding,urinarysymptoms,
andgastrointestinalsymptoms.Theymaybeasymptomaticandfoundonroutinephysical
examinationorultrasoundscan.
Formoreinformation,seeBorderlineOvarianCancer.

Malignantgermcelltumors
Malignantgermcelltumors(GCTs),whichincludedysgerminoma,endodermalsinustumor,malignant
teratoma,embryonalcarcinoma,andchoriocarcinoma,arethoughttoderivefromprimitivegermcells
intheembryonicgonad.GCToftheovaryismuchrarerthanGCTofthetestisinmales,andmuchof
thedevelopmentofthemanagementapproachhasbeenbasedonexperiencewithmaleGCT.
Commoncharacteristicsofthesetumorsincluderapidgrowth,apredilectionforlymphaticspread,
frequentmixturesoftumortypes,andapredominantlyunilateralpatternofovarianinvolvement
(exceptfordysgerminoma).GCTismuchmorecommoninyoungwomenbutoccasionallyoccursin
infantsandolderwomen.

ManyGCTsproducetumormarkersthatcanbemeasuredinthebloodandthenusedtomonitor
responsetotreatmentandforfollowupcare.Endodermalsinustumorssecretealphafetoproteinand
choriocarcinoma,anddysgerminomasoccasionallysecretebetahumanchorionicgonadotropin
(bHCG).Dysgerminomamaysecretelactatedehydrogenaseandplacentalalkalinephosphatase.
Nofactorshavebeenestablishedrelatedtoetiology,apartfromanincreasedincidenceassociated
withdysgeneticgonads.
Althoughthesetumorsmaybeasymptomaticandpresentasapalpablemass,manypatientspresent
withabdominalpain.Themassmayleadtoacutepainduetotorsion,rupture,orhemorrhage,or,
patientsmayhaveabdominaldistension,vaginalbleeding,orfever.
MostarestageIandconfinedtotheovaryatthetimeofdiagnosis.
Dysgerminoma
ThisisthemostcommonmalignantGCTandrepresents35%ofallovarianmalignancies.Ninety
percentoccurinpeopleyoungerthan30years,and75%occurinthesecondandthirddecades,with
amedianageof22years.
Dysgerminomasarebilateralin1035%ofcases.Fivepercentoccurinphenotypicfemaleswith
abnormalgonads.Theymayhavea46XYkaryotypewithpuregonadaldysgenesisorandrogen
insensitivitysyndrome,or,theymayhavea45X,46XYkaryotypewithmixedgonadaldysgenesis.
Dysgerminomasmaybelargeandusuallyaresolid,withasmoothexternalsurfaceandafleshypink
tancolorinside.Themajorityareconfinedtotheovaryatdiagnosis,butapproximately25%of
otherwisestageIdysgerminomashavelymphnodemetastasis.
Formoreinformation,seeOvarianDysgerminomas.
Cysticteratoma
Teratomasaregermcelltumorscommonlycomposedofmultiplecelltypesderivedfromoneormore
ofthe3germlayers.Inconsistentnomenclatureoftenconfusesdiscussionsofvarioussubtypesof
teratomas.ThewordisderivedfromtheGreekteras,meaningmonster,whichVirchowcoinedinthe
firsteditionofhisbookontumorspublishedin1863.[10]Teratomasrangefrombenign,well
differentiated(mature)cysticlesionstothosethataresolidandmalignant(immature).Additionally,
teratomasmaybemonodermalandhighlyspecialized.Rarely,withinsomematureteratomascertain
elements(mostcommonlysquamouscomponents)undergomalignanttransformation.
In1831,Leblanccoinedthetermdermoidcystintheveterinaryliteraturewhenheremovedalesion
thatresembledskinatthebaseofahorse'sskull,whichhecalledakystedermoid.[11]Bothdermoid
andteratoma,termsnowmorethanacenturyold,remainingeneraluseandoftenareused
interchangeablywithvariouspreferencesamongsubspecialties.Theearliestimplicationswerethat
dermoidscomprisedelementssimilartoskinanditsappendages,whereasteratomashadnosuch
limits.Dermoidsnowarerecognizedasoftenbeingtrigeminalandcontainingpracticallyanytypeof
tissue.
Forthosewhocontinuetomakeadistinction,dermoidsaretumorsthatmaintainratherorderly
arrangements,withwelldifferentiatedectodermalandmesodermaltissuessurroundingendodermal
components.Teratomas,specificallysolidteratomas,areessentiallydevoidoforganizationthus,the
presenceofsomedegreeoforganization,ahighdegreeofcellulardifferentiation,andcysticstructure
differentiatesdermoidsfromteratomas(seetheimagesbelow).[10]

Maturecysticteratomaoftheovaryexhibitingmultipletissuetypes.

ViewMediaGallery

Maturecysticteratomaoftheovarywithhair,sebaceousmaterial,andthyroidtissue.

ViewMediaGallery
Formoreinformation,seeTeratoma,Cystic.
Immatureteratoma
ThisisthesecondmostcommonGCT.Itoccursmostlyinfemalesaged1020yearsbutmayoccur
aftermenopause.Thetumorspreadsmostcommonlytoperitonealsurfaces.
Othergermcelltumors
Endodermalsinustumoroccursatameanageof18years,andonethirdoccurbeforepuberty.
Embryonalcarcinomaandchoriocarcinomaareextremelyrare.

Sexcordstromaltumors
TheseincludetumorsarisingfromthesexcordsgranulosacellsSertolicellsandthespecialized
stromaofthegenitalridge,theca,andLeydigcells.Theycomprisefewerthan5%ofallovarian

tumors.
AlthoughgranulosacelltumorsaremalignantandSertoliLeydigcelltumorslessso,theybehaveina
muchlessmalignantfashionthanepithelialovariancancers.Benigntumorsinthegroupinclude
thecomaandfibroma.GranulosacelltumorsandpureSertolicelltumorscommonlysecreteestrogen,
whileLeydigcelltumorsandcombinedSertoliLeydigtumorsoftensecreteandrogens.
Granulosacelltumor
Thisisthemostcommonmalignantsexcordstromaltumor.Ninetypercentofgranulosacelltumors
arestageIatthetimeofdiagnosis.Thistumoraccountforapproximately2%ofallovariantumors
andcanbedividedintoadult(95%)andjuvenile(5%)typesbasedonhistologicfindings.Juvenile
granulosacelltumorisavariantofgranulosacelltumorthatisrarelymalignant.Itmostoftenpresents
inyounggirlswithisosexualprecociouspuberty.Thetumorisusuallyunilateralandconfinedtothe
ovaryandcanbemanagedwithsurgeryalone.
Granulosacelltumorcanoccuratanyage,withameanageoftheearly50s.Becauseofthe
secretionofestrogen,thepresentingfeaturesdependonthepatient'sage.Prepubertalgirlstypically
presentwithprecocioussexualdevelopment,womenofreproductiveagehaveheavyorirregular
periods,andpostmenopausalwomenmayhavepostmenopausalbleeding.Atallages,thetumormay
presentwithacuteabdominalpainduetoruptureorhemorrhage.
Thetumorsvaryinsizeandmaybesolidorpartiallycystic(seetheimagebelow).

Granulosacelltumorexcisedfromawomanaged44years.Notetheyellowishtumorthathaserodedthrough,
ontothesurfaceoftheovary.

ViewMediaGallery
Thecutsurfacemaybegraywhiteoryellow,dependingonlipidcontent.Necrosisandhemorrhage
oftenarepresent,withcysticcompartmentsfilledwithfluidorclottedblood(seetheimagebelow).

Thisphotoshowsagranulosacelltumor,withthecutsurfaceshowingclassicfeaturesofahemorrhagiccystand
yellowishsolidcomponent.

ViewMediaGallery
Themicroscopicfeaturesaregranulosacellsinawidevarietyofpatterns,andcharacteristicCall
Exnerbodiesmaybepresent.
Formoreinformation,seeGranulosaThecaCellTumors.
SertoliLeydigcelltumor
Thesetumorsarerare.Theyareaformoflowgrademalignancythattypicallyproducesandrogens
andrarelyestrogens.

Otherraretumors
Smallcellcarcinomaisararetypeofcarcinomathatoccursinfemalesaged246years.Itoftenis
associatedwithhypercalcemia.
Themostcommonformofsarcomaintheovaryisthemixedmesodermalsarcomaor
carcinosarcoma.
Metastatictumorsoftheovaryarisefromdirectextensionandspreadwithinthebloodstreamor
lymphaticsystemorwithintheperitonealcavity.Sitesoforiginincludetheendometriumcervixand
nongynecologicsitessuchasbreast,colon,andstomach.TheclassicKrukenbergtumorrefersto
bilateralenlargementoftheovariesfrommetastasesfromasignetringcarcinomaofthestomach.

Etiology
Theprecisecauseofovariancancerisunknown,butseveralriskandcontributingfactorshavebeen
identified.
HippisleyCoxandCouplanddevelopedanalgorithmtodetermineriskofovariancancerinwomen
withandwithoutsymptoms.[12]Intheircohortstudy,10%ofwomenwiththehighestpredictedrisk
had63%ofallovariancancersdiagnosedoverthenext2years.

Reproductivefactors
Parityisanimportantriskfactor.Theriskofepithelialovariancancerisincreasedinwomenwhohave
nothadchildrenandpossiblythosewithearlymenarcheorlatemenopause.Womenwhohavebeen

pregnanthavea50%decreasedriskfordevelopingovariancancercomparedwithnulliparous
women.Multiplepregnanciesofferanincreasinglyprotectiveeffect.Oralcontraceptiveusedecreases
theriskofovariancancersignificantly.
Thesefactorssupporttheideathatriskforovariancancerisrelatedtoovulation.Twotheories
regardingthisrelationshiphavebeenproposed.Theincessantovulationtheorysuggeststhat
repeatedovarianepithelialtraumacausedbyfollicularruptureandsubsequentepithelialrepairresults
ingeneticalterationswithinthesurfaceepithelium.Thegonadotropintheoryproposesthatpersistent
stimulationoftheovariesbygonadotropins,coupledwithlocaleffectsofendogenoushormones,
increasessurfaceepithelialproliferationandsubsequentmitoticactivity.
Thus,theprobabilityofovariancancermayberelatedtothenumberofovulatorycycles,and
conditionsthatsuppresstheovulatorycyclemayplayaprotectiverole.Ovulationsuppressionhas
beenshowntodecreasecancerincidence.Althoughtreatmentwithagentsthatinduceovulationin
womenwithinfertilityhasbeensuggestedtoincreasetheincidenceofepithelialovariancancer,thisis
unproven.

Geneticfactors
Familyhistoryplaysanimportantroleintheriskofdevelopingovariancancer.Thelifetimeriskfor
developingovariancanceris1.6%inthegeneralpopulation.Thiscompareswitha45%riskwhen1
firstdegreefamilymemberisaffected,risingto7%when2relativesareaffected.From510%of
casesofovariancanceroccurinanindividualwithafamilyhistoryofthedisease.Onlyasmall
percentageofthesepatientshaveaninheritedgeneticabnormality,andtheriskofthisoccurrence
increaseswiththestrengthofthefamilyhistory.Hereditaryepithelialovariancanceroccursata
youngerage(approximately10yearsyounger)thannonhereditaryepithelialovariancancer,butthe
prognosismaybesomewhatbetter.
IntegratedgenomicanalysesbytheCancerGenomeAtlasResearchNetworkhaverevealedhigh
gradeserousovariancancerischaracterizedbyTP53mutationsinalmostalltumors.Thefindings
alsoincludethelowprevalencebutstatisticallyrecurrentsomaticmutationsin9furthergenes,
includingNF1,BRCA1,BRCA2,RB1,andCDK12,alongwith113significantfocalDNAcopynumber
aberrationsandpromotermethylationeventsinvolving168genes.Pathwayanalysesrevealed
defectivehomologousrecombinationinabouthalfofalltumors,andthatNOTCHandFOXM1
signalingareinvolvedinserousovariancancerpathophysiology.[13]
EvidencefromtheCancerGenomeAtlasNetworkshowedthatserousovariantumorsandbreast
basalliketumorssharedanumberofmolecularcharacteristics,suchasthetypesandfrequenciesof
genomicmutations,suggestingthatovarianandbreastcancermayhavearelatedetiologyand
potentiallysimilarresponsivenesstosomeofthesametherapies.[14]
Atleasttwosyndromesofhereditaryovariancancerareclearlyidentified,involvingeither(1)
disordersofthegenesassociatedwithbreastcancer,BRCA1andBRCA2,or(2)morerarely,genes
withintheLynchIIsyndromecomplex.Breast/ovariancancersyndromeisassociatedwithearlyonset
ofbreastorovariancancer.Inheritancefollowsanautosomaldominanttransmission.Itcanbe
inheritedfromeitherparent.

1 MostcasesarerelatedtotheBRCA1genemutation.BRCA1isatumorsuppressorgenethatinhibits
cellgrowthwhenfunctioningproperlytheinheritanceofmutantallelesofBRCA1leadstoa
considerableincreaseinriskfordevelopingovariancancer.
Approximately1personin4000inthegeneralpopulationcarriesamutationofBRCA1.Some
populationshaveamuchhigherrateofBRCA1andBRCA2mutations,especiallyAshkenaziJews.In
familieswith2firstdegreerelatives(mother,sister,ordaughter)withpremenopausalepithelialovarian

cancer,thelikelihoodofafemalerelativehavinganaffectedBRCA1orBRCA2geneisashighas
40%.Theprobabilityismuchlowerwhenthediseaseoccursinrelativespostmenopausally.
IndividualswithaBRCA1genemutationhavea5085%lifetimeriskofdevelopingbreastcancerand
a1545%riskofdevelopingepithelialovariancancer.ThosewithaBRCA2genemutationhavea50
85%lifetimeriskofdevelopingbreastcanceranda1020%riskofdevelopingepithelialovarian
cancer.FamilieswithBRCA2mutationsareatriskfordevelopingcanceroftheprostate,larynx,
pancreas,andmalebreast.
GermlinemutationsintheBRCA1andBRCA2genesareassociatedwithincreasedrisksofbreast
andovariancancershowever,inaninvestigationofacommongeneticvariationatthe9p22.2locus,
adecreasedriskofovariancancerwasnotedincarriersofaBRCA1orBRCA2mutation.[15]

2 FamilieswithLynchIIsyndromeorhereditarynonpolyposiscolorectalcancerarecharacterizedbya

highriskfordevelopingcolorectal,endometrial,stomach,smallbowel,breast,pancreas,andovarian
cancers.Thissyndromeiscausedbymutationsinthemismatchrepairgenes.Mutationshavebeen
demonstratedinmismatchrepairgenesMSH2,MLH1,PMS1,andPMS2.
Womenwithahistoryofbreastcancerhaveanincreasedriskofepithelialovariancancer.
InastudybyRafneretal,wholegenomesequencingidentifiedararemutationinBRIP1,which
behaveslikeaclassicaltumorsuppressorgeneinovariancancer.[16]Thisallelewasalsoassociated
withbreastcancer.

Previoushormonetherapy
Anationwideprospectivecohortstudyover10yearsthatincludedallDanishwomenaged5079
yearsconcludedthatriskforovariancancerisincreasedwithhormonetherapy,regardlessofduration
ofuse,formulation,estrogendose,regimen,progestintype,andadministrationroute.[17]Nearly1
millionwomenwithouthormonesensitivecancerorbilateraloophorectomywerefollowed.Inan
averageof8yearsoffollowup,3068ovariancancersweredetected,ofwhich2681wereepithelial
cancers.
Currentusersofhormoneshadincidencerateratiosforallovariancancersof1.38(95%confidence
interval[CI],11.261.51)comparedwithwomenwhonevertookhormonetherapy.Riskdeclinedas
yearssincelasthormoneuseincreased.Incidenceratesincurrentandneverusersofhormoneswere
0.52and0.40per1000years,respectively.Thistranslatestoapproximatelyoneextraovariancancer
forapproximately8300womentakinghormonetherapyeachyear.

Otherfactors
Theuseoftalcumpowderonthevulvaandperineummaybeassociatedwithincreasedriskof
epithelialovariancancer.[18]Highlactoseconsumptionhasbeenassociatedwithincreasedriskof
ovariancancer,butevidencelinkinglactoseandspecificdairyproductswithovariancancerremains
contradictory.[19,20]

Epidemiology
IntheUnitedStates,theincidenceofovariancanceris12.1per100,000womenperyear,basedon
20082012cases.[21]Theincidenceofovariancancerhasbeenslowlydecreasingsincethemid
1980sitdecreasedby0.9%peryearfrom2007to2011.[22]Ovariancancerismorecommonin

whitesthaninAfricanAmericans(12.8versus9.8casesper100,000womenperyear,respectively).
[21]

Epithelialovariancancercanoccuringirlsasyoungas15years,butthemeanageatdiagnosisis63
years,andmostcasesarediagnosedinwomen5564yearsofage.IntheUnitedStates,the
estimatedlifetimeriskis1.3%.[21]
TheAmericanCancerSocietyestimatesthat22,280newcasesofovariancancerwillbediagnosedin
2016and14,240womenwilldiefromthedisease.[22]Althoughovariancanceristhe17thmost
commoncancerinwomen,itisthefifthmostcommoncauseofcancerdeathinwoman,accounting
for5%ofcancerdeathsmorethananyothergynecologiccancer.[22,21]From2007to2011,the
deathratefromovariancancerdecreasedby2.0%peryearinwhitewomenandwasstableinblack
women.[22]

Internationalstatistics
Internationally,theincidencerangesfrom3.1casesper100,000womeninJapanto21casesper
100,000womeninSweden.Aroundtheworld,morethan200,000womenareestimatedtodevelop
ovariancancereveryyearandabout100,000diefromthedisease.
Epithelialovariancanceroccursmostcommonlyinwhitewomenintheindustrializedcountriesof
northernandwesternEuropeandNorthAmericaandleastcommonlyinIndiaandAsia.Asianwomen
havelowriskunlesstheyrelocatetoNorthAmericaorEurope.ScandinavianandNorwegianwomen
havethehighestrisk.

Prognosis
Althoughthe5yearsurvivalrateforovariancancerhasimprovedsignificantlyinthepast30years,
theprognosisforovariancancerremainspooroverall,witha46%5yearsurvivalrate.Theprognosis
ofovariancanceriscloselyrelatedtothestageatdiagnosis,[23,24]asdeterminedaccordingtothe
stagingsystemdevelopedbytheInternationalFederationofGynecologyandObstetrics(FIGO).(See
Staging.)Approximately20%,5%,58%,and17%ofwomenpresentwithstageI,II,III,andIV,
respectively.
The5yearsurvivalrates(roundedtothenearestwholenumber)forepithelialovariancarcinomaby
FIGOstageareasfollows:
StageIA87%
StageIB71%
StageIC79%
StageIIA67%
StageIIB55%
StageIIC57%
StageIIIA41%
StageIIIB25%
StageIIIC23%
StageIV11%
Overallsurvivalrate46%
Bakhruetalfoundpoorersurvivalamongpatientswithovariancanceranddiabetes.Althoughthe
underlyingreasonforthisassociationisunknown,furtherstudiesareneeded.[25]

Amongwomenwithhighgradeserousovariancancer,BRCA2mutationbutnotBRCA1deficiency
wasassociatedwithimprovedsurvival,improvedchemotherapyresponse,andgenomeinstability
comparedwithBRCAwildtype.[26]
AstudybyBoltonetalfoundimproved5yearoverallsurvivalamongcarriersofBRCA1orBRCA2,
withBRCA1havingthebestprognosis.[27]

PrognosisofTumorsofLowMalignantPotential
Overallsurvivalrateat5yearsaccordingtoFIGOisshownbelow.Othershavereportedbetter
survivalrateswith5year,10year,15year,and20yearsurvivalforpatientswithserousLMPas97%,
95%,92%,and89%,respectively.
FiveyearsurvivalrateforLMPtumorsbyFIGOstage(survivalpercentagesroundedtonearestwhole
number)areasfollows:
StageIA93%
StageIB90%
StageIC91%
StageIIA88%
StageIIB86%
StageIIC100%
StageIIIA29%
StageIIIB75%
StageIIIC62%
StageIV30%
Overallsurvivalrate86%

PatientEducation
Forpatienteducationresources,seetheCancerCenterandtheWomen'sHealthCenter.Also,see
thepatienteducationarticlesOvarianCancerandOvarianCysts.
ClinicalPresentation
References

1.GoffBA,MandelLS,DrescherCW,UrbanN,GoughS,SchurmanKM,etal.Developmentofan
ovariancancersymptomindex:possibilitiesforearlierdetection.Cancer.2007Jan15.
109(2):2217.[Medline].
2.RyersonAB,EhemanC,BurtonJ,McCallN,BlackmanD,SubramanianS,etal.Symptoms,
diagnoses,andtimetokeydiagnosticproceduresamongolderU.S.womenwithovariancancer.
ObstetGynecol.2007May.109(5):105361.[Medline].
3.[Guideline]MoyerVA.Screeningforovariancancer:U.S.PreventiveServicesTaskForce
reaffirmationrecommendationstatement.AnnInternMed.2012Dec18.157(12):9004.
[Medline].[FullText].
4.FleischerA.Ovariancancer.FleischerAC,JavittMC,JeffreyRBJr,etal.ClinicalGynecologic
Imaging.Philadelphia,Pa:LippincottWilliams&Wilkins1996.107.