2022
Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers
Batalini F, Gulhan DC, Mao V, Tran A, Polak M, Xiong N, Tayob N, Tung NM, Winer EP, Mayer EL, Knappskog S, Lønning PE, Matulonis UA, Konstantinopoulos PA, Solit DB, Won H, Eikesdal HP, Park PJ, Wulf GM. Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers. Clinical Cancer Research 2022, 28: of1-of10. PMID: 36048535, PMCID: PMC9623231, DOI: 10.1158/1078-0432.ccr-22-0749.Peer-Reviewed Original ResearchConceptsHomologous recombination deficiencyTriple-negative breast cancerMutational signature 3Ovarian cancerImproved progression-free survivalPARP inhibitorsPanel sequencingHigh-grade serous ovarian cancerPI3K inhibitor buparlisibPhase Ib trialProgression-free survivalIdentification of patientsRoutine clinical careSignature 3Serous ovarian cancerPARP inhibitor olaparibSame patient sampleIb trialObjective responseTNBC patientsBreast cancerBRCA1/2 mutationsClinical careInstability scoreGenomic instability score
2020
Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer
Waks AG, Cohen O, Kochupurakkal B, Kim D, Dunn CE, Buendia J, Wander S, Helvie K, Lloyd MR, Marini L, Hughes ME, Freeman SS, Ivy SP, Geradts J, Isakoff S, LoRusso P, Adalsteinsson VA, Tolaney SM, Matulonis U, Krop IE, D’Andrea A, Winer EP, Lin NU, Shapiro GI, Wagle N. Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer. Annals Of Oncology 2020, 31: 590-598. PMID: 32245699, PMCID: PMC7946408, DOI: 10.1016/j.annonc.2020.02.008.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerPlatinum chemotherapyDNA-damaging therapyMechanisms of resistanceBreast cancerMetastatic breast cancer patientsBreast cancer patientsTumor DNA sequencingNovel sequence alterationsWhole-exome sequencingDNA-damaging therapiesTreatment failureCancer patientsFunctional statusDisease progressionTumor biopsiesClinical cohortImmunohistochemical stainingSubsequent linesBRCA1/2 mutationsTherapeutic benefitPatientsUseful biomarkerFunctional assessmentTumor sections
2019
Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial
Konstantinopoulos PA, Barry WT, Birrer M, Westin SN, Cadoo KA, Shapiro GI, Mayer EL, O'Cearbhaill RE, Coleman RL, Kochupurakkal B, Whalen C, Curtis J, Farooq S, Luo W, Eismann J, Buss MK, Aghajanian C, Mills GB, Palakurthi S, Kirschmeier P, Liu J, Cantley LC, Kaufmann SH, Swisher EM, D'Andrea AD, Winer E, Wulf GM, Matulonis UA. Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial. The Lancet Oncology 2019, 20: 570-580. PMID: 30880072, PMCID: PMC7025391, DOI: 10.1016/s1470-2045(18)30905-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Ovarian EpithelialDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFemaleGenome, HumanHumansMaximum Tolerated DoseMiddle AgedMutationOvarian NeoplasmsPhosphoinositide-3 Kinase InhibitorsPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsThiazolesTreatment OutcomeConceptsEpithelial ovarian cancerPhase 2 dosePI3K inhibitor alpelisibPrimary peritoneal cancerPhase 1b trialRecurrent breast cancerGermline BRCA mutationsOvarian cancerBreast cancerDose levelsPeritoneal cancerBRCA mutationsFallopian tubeCommon treatment-related grade 3High-grade serous histologyTreatment-related grade 3Breast Cancer Research FoundationDecreased neutrophil countDose-escalation cohortsDose-expansion cohortsTreatment-related deathsTriple negative histologyResponse Evaluation CriteriaSolid Tumors 1.1Key eligibility criteria
2017
Phase I dose escalation study of the PI3kinase pathway inhibitor BKM120 and the oral poly (ADP ribose) polymerase (PARP) inhibitor olaparib for the treatment of high-grade serous ovarian and breast cancer
Matulonis U, Wulf G, Barry W, Birrer M, Westin S, Farooq S, Bell-McGuinn K, Obermayer E, Whalen C, Spagnoletti T, Luo W, Liu H, Hok R, Aghajanian C, Solit D, Mills G, Taylor B, Won H, Berger M, Palakurthi S, Liu J, Cantley L, Winer E. Phase I dose escalation study of the PI3kinase pathway inhibitor BKM120 and the oral poly (ADP ribose) polymerase (PARP) inhibitor olaparib for the treatment of high-grade serous ovarian and breast cancer. Annals Of Oncology 2017, 28: 512-518. PMID: 27993796, PMCID: PMC5834157, DOI: 10.1093/annonc/mdw672.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAminopyridinesBRCA1 ProteinBRCA2 ProteinBreast NeoplasmsDose-Response Relationship, DrugFemaleGerm-Line MutationHumansMiddle AgedMorpholinesNeoplasm GradingNeoplasm Recurrence, LocalOvarian NeoplasmsPhosphoinositide-3 Kinase InhibitorsPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesConceptsGermline BRCA mutationsOvarian cancerStudy treatmentPARP inhibitorsRandomized phase II studyDose-expansion cohortsPhase II studyPhase I trialDose-escalation designWild-type patientsBiomarkers of responsePARP inhibitor combinationsCombination of BKM120Polymerase inhibitor olaparibPoly (ADP-ribose) polymerase (PARP) inhibitor olaparibPI3K inhibitorsAdditional DLTsOlaparib 300Preclinical synergyRecurrent breastEscalation studyII studyI trialClinical benefitBRCA mutations
2016
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE. Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer. Journal Of Clinical Oncology 2016, 34: 1460-1468. PMID: 26976419, PMCID: PMC4872307, DOI: 10.1200/jco.2015.65.0747.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overBreast NeoplasmsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, BRCA1Genes, BRCA2Genetic Predisposition to DiseaseGenetic TestingGerm-Line MutationHigh-Throughput Nucleotide SequencingHumansJewsMiddle AgedNeoplasm StagingOvarian NeoplasmsPredictive Value of TestsPrevalenceProspective StudiesRetrospective StudiesRisk FactorsTriple Negative Breast NeoplasmsConceptsCancer predisposition genesTriple-negative breast cancerBreast cancer predisposition genesBreast cancerPredisposition genesGermline mutationsOvarian cancerNext-generation sequencingBRCA1/2 mutationsCancer susceptibility genesSingle cancer centerFamily cancer historyBreast/ovarian cancerOvarian cancer predisposition genesPredictors of mutationsSusceptibility genesSelect patientsSequential patientsAshkenazi Jewish ancestryCancer CenterCancer historyClinical managementFamily historyBreast/ovarian cancer susceptibility geneOvarian cancer susceptibility genes
2014
Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study
Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, Luo W, Quy P, Whalen C, Obermayer L, Lee H, Winer EP, Kohn EC, Ivy SP, Matulonis UA. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. The Lancet Oncology 2014, 15: 1207-1214. PMID: 25218906, PMCID: PMC4294183, DOI: 10.1016/s1470-2045(14)70391-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Ovarian EpithelialCisplatinConfidence IntervalsDisease-Free SurvivalDose-Response Relationship, DrugDrug Administration ScheduleFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalNeoplasms, Glandular and EpithelialOvarian NeoplasmsPhthalazinesPiperazinesQuinazolinesRisk AssessmentSurvival AnalysisTreatment OutcomeConceptsProgression-free survivalRecurrent platinum-sensitive ovarian cancerPlatinum-sensitive ovarian cancerPhase 2 studyOvarian cancerOlaparib monotherapyMedian progression-free survivalGermline BRCA statusPhase 2 dosePrimary peritoneal cancerRecurrent ovarian cancerPhase 2 trialPhase 3 trialSide effect profilePhase 1 trialUS academic medical centersPatient-reported outcomesEndometrioid ovarian cancerGermline BRCA1/2 mutationsAnti-angiogenic therapyAnti-angiogenic agentsCombination of olaparibAcademic medical centerNational Cancer InstituteVEGF receptor 1Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors
Balmaña J, Tung N, Isakoff S, Graña B, Ryan P, Saura C, Lowe E, Frewer P, Winer E, Baselga J, Garber J. Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors. Annals Of Oncology 2014, 25: 1656-1663. PMID: 24827126, DOI: 10.1093/annonc/mdu187.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsSolid tumorsBRCA1/2 mutationsDay 1Overall objective response rateBID days 1Grade 3 neutropeniaObjective response ratePhase I trialTreatment of patientsGermline BRCA1/2 mutationsColony-stimulating factorWarrants further investigationAdvanced breastHematologic supportMeasurable diseaseOral olaparibAdverse eventsI trialTreatment cohortsLipase elevationCisplatin dosesFrequent gradePreliminary efficacyStandard treatment
2013
A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer
Liu JF, Tolaney SM, Birrer M, Fleming GF, Buss MK, Dahlberg SE, Lee H, Whalen C, Tyburski K, Winer E, Ivy P, Matulonis UA. A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. European Journal Of Cancer 2013, 49: 2972-2978. PMID: 23810467, PMCID: PMC3956307, DOI: 10.1016/j.ejca.2013.05.020.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCapsulesCarcinoma, Ovarian EpithelialDiarrheaDose-Response Relationship, DrugDrug Administration ScheduleFatigueFemaleHumansMiddle AgedNauseaNeoplasm Recurrence, LocalNeoplasms, Glandular and EpithelialOvarian NeoplasmsPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsQuinazolinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneReceptors, Vascular Endothelial Growth FactorTabletsTreatment OutcomeConceptsTriple-negative breast cancerOvarian cancer patientsOverall response rateCombination of cediranibCancer patientsBreast cancerDose levelsMetastatic triple-negative breast cancerEvaluable breast cancer patientsPARP inhibitorsClinical benefit rateGrade 3 fatigueGrade 3 hypertensionPhase 2 dosingVascular endothelial growth factor receptorResponse Evaluation CriteriaSolid Tumors 1.1Endothelial growth factor receptorPhase 1 trialBreast cancer patientsDose-escalation designHighest dose levelPolymerase inhibitor olaparibCA125 criteriaGrowth factor receptor
2003
Attitudes, knowledge, risk perceptions and decision‐making among women with breast and/or ovarian cancer considering testing for BRCA1 and BRCA2 and their spouses
Bluman LG, Rimer BK, Sterba K, Lancaster J, Clark S, Borstelmann N, Iglehart JD, Winer EP. Attitudes, knowledge, risk perceptions and decision‐making among women with breast and/or ovarian cancer considering testing for BRCA1 and BRCA2 and their spouses. Psycho-Oncology 2003, 12: 410-427. PMID: 12833555, DOI: 10.1002/pon.653.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedATP Binding Cassette Transporter, Subfamily G, Member 2ATP-Binding Cassette TransportersBRCA1 ProteinBRCA2 ProteinBreast NeoplasmsDecision MakingDNA Mutational AnalysisFemaleGenetic Predisposition to DiseaseGenetic TestingHealth Knowledge, Attitudes, PracticeHumansMaleMiddle AgedNeoplasm ProteinsNeoplasm Recurrence, LocalOvarian NeoplasmsRiskSpousesConceptsGenetic testingBreast cancer susceptibilityOvarian cancerBreast cancerCancer susceptibilityInvolvement of spousesWives' breast cancerBRCA2 mutationsBRCA2 testingFuture interventionsCancerWomenPersonal historyBRCA2Cancer geneticsOne-thirdBRCA1BreastSpousesInvolvementMost spousesDecision-making processTestingSusceptibilityMutations
2002
Pre-Counseling Education Materials for BRCA Testing: Does Tailoring Make a Difference?
Skinner CS, Schildkraut JM, Berry D, Calingaert B, Marcom PK, Sugarman J, Winer EP, Iglehart JD, Futreal PA, Rimer BK. Pre-Counseling Education Materials for BRCA Testing: Does Tailoring Make a Difference? Genetic Testing And Molecular Biomarkers 2002, 6: 93-105. PMID: 12215248, DOI: 10.1089/10906570260199348.Peer-Reviewed Original ResearchConceptsGenetic testingOvarian cancer susceptibilityTumor RegistryMean ageOvarian cancer gene BRCA1Ovarian cancerFamily historyMutation carriersBRCA testingBaseline surveyCancer susceptibilityEstimation of riskBehavioral targetsPrint materialsGreater improvementBreastFollowup surveyEducation materialsWomenGenes BRCA1Decision aidRiskBRCA1
2000
Testing for Hereditary Breast and Ovarian Cancer in the Southeastern United States
Miron A, Schildkraut J, Rimer B, Winer E, Skinner C, Futreal P, Culler D, Calingaert B, Clark S, Marcom P, Iglehart J. Testing for Hereditary Breast and Ovarian Cancer in the Southeastern United States. Annals Of Surgery 2000, 231: 624-634. PMID: 10767783, PMCID: PMC1421049, DOI: 10.1097/00000658-200005000-00002.Peer-Reviewed Original ResearchConceptsProphylactic surgeryPreventive surgeryOvarian cancerFree genetic testingProspective clinical trialsBreast cancer patientsHereditary breast cancerPositive test resultsUncertain clinical significanceMore heterogeneous populationsBaseline characteristicsCancer patientsBaseline questionnaireClinical trialsTime of entryBreast cancerClinical significanceHeterogeneous syndromeSurgeryHereditary breastNumber of womenDeleterious gene mutationsBRCA2 genesGenetic testingSpecial populations
1999
Attitudes, knowledge, and risk perceptions of women with breast and/or ovarian cancer considering testing for BRCA1 and BRCA2.
Bluman L, Rimer B, Berry D, Borstelmann N, Iglehart J, Regan K, Schildkraut J, Winer E. Attitudes, knowledge, and risk perceptions of women with breast and/or ovarian cancer considering testing for BRCA1 and BRCA2. Journal Of Clinical Oncology 1999, 17: 1040-6. PMID: 10071299, DOI: 10.1200/jco.1999.17.3.1040.Peer-Reviewed Original ResearchConceptsOvarian cancerBRCA2 mutationsHigh-risk womenPercent of womenBaseline questionnairePhysician referralCancer riskChallenges cliniciansGenetic testingKnowledge deficitsWomenCancerGene mutationsBreastBRCA2PatientsBaseline knowledgeRiskBRCA1Cancer geneticsTrialsRisk perceptionHigher proportionMutationsPerception of risk
1998
Testing for the BRCA1 and BRCA2 Breast-Ovarian Cancer Susceptibility Genes
Tengs TO, Winer EP, Paddock S, Aguilar-Chavez O, Berry DA. Testing for the BRCA1 and BRCA2 Breast-Ovarian Cancer Susceptibility Genes. Medical Decision Making 1998, 18: 365-375. PMID: 10372578, DOI: 10.1177/0272989x9801800402.Peer-Reviewed Original ResearchAdultAgedBreast NeoplasmsDecision Support TechniquesFemaleGenes, BRCA1Genes, Tumor SuppressorGenetic Predisposition to DiseaseGenetic TestingHumansIncidenceMarkov ChainsMastectomyMiddle AgedOvarian NeoplasmsOvariectomyPredictive Value of TestsQuality-Adjusted Life YearsRisk AssessmentSurvival AnalysisUnited StatesSequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk.
Frank TS, Manley SA, Olopade OI, Cummings S, Garber JE, Bernhardt B, Antman K, Russo D, Wood ME, Mullineau L, Isaacs C, Peshkin B, Buys S, Venne V, Rowley PT, Loader S, Offit K, Robson M, Hampel H, Brener D, Winer EP, Clark S, Weber B, Strong LC, Thomas A. Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. Journal Of Clinical Oncology 1998, 16: 2417-25. PMID: 9667259, DOI: 10.1200/jco.1998.16.7.2417.Peer-Reviewed Original ResearchInformed Consent for BRCA1 and BRCA2 Testing
Rimer B, Sugarman J, Winer E, Bluman L, Lerman C. Informed Consent for BRCA1 and BRCA2 Testing. Breast Disease 1998, 10: 99-114. PMID: 15687553, DOI: 10.3233/bd-1998-101-212.Peer-Reviewed Original Research
1997
Probability of Carrying a Mutation of Breast-Ovarian Cancer Gene BRCA1 Based on Family History
Berry D, Parmigiani G, Sanchez J, Schildkraut J, Winer E. Probability of Carrying a Mutation of Breast-Ovarian Cancer Gene BRCA1 Based on Family History. Journal Of The National Cancer Institute 1997, 89: 227-237. PMID: 9017003, DOI: 10.1093/jnci/89.3.227.Peer-Reviewed Original Research