Fig.19.31Timetorecurrenceofbreastcancers.Thehazardratioreflectstheriskofrecurrenceofeachmoleculartypeofbreastcanceratvariouspointsintimeafterdiagnosis.ER-negativecancersusuallyrecurwithinthefirst8years.Patientswhosurvivebeyondthisintervalarelikelycured.Incontrast,ER-positivecancershavealowerrateofrecurrence,butremainatriskdecadesaftertheprimarydiagnosis.
19.8 ), as already proven by marked improvement in survival of women with HER2-positive carcinomas following the introduction of therapies that target HER2. Newer approaches to targeted therapy include inhibition of alternative DNA repair pathways in BRCA-mutated cancers and blockage of the PI3K-AKT-signaling pathway. Immune checkpoint blockade therapy (Chapter 6), is under evaluation in patients with breast cancer. It is hoped that such new approaches will improve outcomes in subtypes that currently have a generally poor prognosis, such as triple negative breast cancer.
ImmunecheckpointBlockingantibodiestoPD-L1,PD-1,andIHCforimmunecheckpointUnderinvestigationinpatientswithproteinsotherimmunecheckpointproteinsproteins—notyetvalidatedtriple-negativebreastcancer
ER, Estrogenreceptor;HRR, homologousrecombinationrepair;IHC, immunohistochemistry;ISH, insituhybridization.
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ThelifetimeriskofdevelopingbreastcancerforanAmericanwomanis1in8.
Amajority(75%)ofbreastcancersarediagnosedaftertheageof50.
Themajorriskfactorsfordevelopingbreastcancerarerelatedtohormonalfactorsandinheritedsusceptibility.
About12%ofallbreastcancersarecausedbyidentifiedgerm-linemutations;BRCA1 andBRCA2 genesaccountforone-halfofthecasesassociatedwithsingle-genemutations.
DCISisaprecursortoinvasiveductalcarcinomaandismostoftenfoundonmammographicscreeningascalcifications.WhencarcinomadevelopsinawomanwithapreviousdiagnosisofuntreatedDCIS,itisusuallyisaninvasiveductalcarcinomainthesamebreast.
LCISisbothamarkerofincreasedriskandaprecursorlesion.WhencarcinomadevelopsinawomanwithapreviousdiagnosisofLCIS,two-thirdsareinthesamebreastandone-thirdisinthecontralateralbreast.
Invasivecarcinomasareclassifiedaccordingtohistologictypeandbiologictype:ER-positive/HER2-negative,HER2-positive,andER/PR/HER2-negative(triple-negative).Thebiologictypesofcancerhaveimportantdifferencesinpatientcharacteristics,grade,mutationprofile,metastaticpattern,responsetotherapy,timetorecurrence,andprognosis.
Prognosisisdependentonthebiologictypeoftumor,stage,andtheavailabilityoftreatmentmodalities.
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