Bisphosphonate use and the risk of breast cancer: a meta-analysis of of published literature

Bisphosphonatesarewidelyusedtopreventandtreatosteoporosisandcancer-inducedbonelossinclinicalpractice.Recently,severalpublishedobservationalstudiesfoundthatwomenwhousedbisphosphonateshadasignificantreductionintheriskofbreastcancercomparedtononusers.However,thefindingswereinconsistent.WesystematicallysearchedMEDLINEandEMBASEdatabasesthroughJune1,2011.Theeligibilitydeterminationandthedataextractionwereconductedindependentlybytwoauthors.Arandom-effectmodelwasusedtoobtainthepooledestimatesofeffect.Weidentifiedtwocohortstudiesandtwocase-controlstudiesthatwereeligibleforanalysis,involving15363breastcancerpatientsand84931bisphosphonateusers.Theresultsofourmetaanalysisrevealthatwomenwhoreceivebisphosphonateshavea15%riskreductionofanybreastcancer(pooledriskratio(RR):0.85,95%confidenceinterval(CI):0.740.98;P=0.03)anda32%riskreductionofinvasivebreastcancer(pooledRR:0.68,95%CI:0.590.80;P<0.001)comparedtononusers.Additionally,therewasasignificantdoseresponserelationshipbetweenthedurationofbisphosphonateuseandbreastcancerrisk.Asignificantlyprotectiveeffectofbisphosphonateswasobservedinpatientsthatusedbisphosphonatesformorethanoneyearbeforethediagnosisofbreastcancercomparedtononusers.Thebisphosphonateusershadariskreductionofbreastcancerby8%(pooledRR:0.92,95%CI:0.870.96;P=0.001)foreachadditionalyearofthedurationofbisphosphonateuse.Theuseofbisphosphonatesmayhaveabeneficialeffectonbreastcancerrisk.