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
2021
Phase II trial of veliparib and temozolomide in metastatic breast cancer patients with and without BRCA1/2 mutations
Xu J, Keenan TE, Overmoyer B, Tung NM, Gelman RS, Habin K, Garber JE, Ellisen LW, Winer EP, Goss PE, Yeap BY, Chabner BA, Isakoff SJ. Phase II trial of veliparib and temozolomide in metastatic breast cancer patients with and without BRCA1/2 mutations. Breast Cancer Research And Treatment 2021, 189: 641-651. PMID: 34417675, DOI: 10.1007/s10549-021-06292-7.Peer-Reviewed Original ResearchConceptsObjective response rateClinical benefit rateProgression-free survivalMedian progression-free survivalMetastatic breast cancer patientsPhase II trialMetastatic breast cancerBreast cancer patientsBRCA1/2 carriersBreast cancerExpansion cohortII trialPrimary endpointPrimary cohortCancer patientsBenefit rateBRCA1/2 mutationsDay 1Longer median progression-free survivalSingle-arm phase II trialCommon grade 3Doses of veliparibPlatinum-naïve patientsPrior platinum therapyBRCA mutation carriersAtezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study
Emens LA, Molinero L, Loi S, Rugo HS, Schneeweiss A, Diéras V, Iwata H, Barrios CH, Nechaeva M, Nguyen-Duc A, Chui SY, Husain A, Winer EP, Adams S, Schmid P. Atezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study. Journal Of The National Cancer Institute 2021, 113: 1005-1016. PMID: 33523233, PMCID: PMC8328980, DOI: 10.1093/jnci/djab004.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerMetastatic triple-negative breast cancerProgression-free survivalPD-L1Tumor immune microenvironmentBreast cancerIntratumoral CD8Nab-paclitaxelClinical benefitImmune microenvironmentImmune cellsBRCA1/2 mutationsAdvanced triple-negative breast cancerStromal tumor-infiltrating lymphocytesNab-paclitaxel 100Immune checkpoint inhibitorsOverall survival benefitTumor-infiltrating lymphocytesMetastatic tumor tissueBRCA1/2 mutation statusCheckpoint inhibitorsOverall survivalSurvival benefitImmune biomarkersClinical activity
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
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
2015
TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer
Isakoff SJ, Mayer EL, He L, Traina TA, Carey LA, Krag KJ, Rugo HS, Liu MC, Stearns V, Come SE, Timms KM, Hartman AR, Borger DR, Finkelstein DM, Garber JE, Ryan PD, Winer EP, Goss PE, Ellisen LW. TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2015, 33: 1902-1909. PMID: 25847936, PMCID: PMC4451173, DOI: 10.1200/jco.2014.57.6660.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBiomarkers, TumorBRCA1 ProteinBRCA2 ProteinCarboplatinCisplatinClass I Phosphatidylinositol 3-KinasesDrug Administration ScheduleFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenomic InstabilityHeterozygoteHumansLoss of HeterozygosityMiddle AgedMutationNeoplasm StagingPhosphatidylinositol 3-KinasesTreatment OutcomeTriple Negative Breast NeoplasmsConceptsMetastatic triple-negative breast cancerGermline BRCA1/2 mutationsPhase II clinical trialTriple-negative breast cancerBRCA1/2 mutationsResponse rateClinical trialsBreast cancerMulticenter phase II clinical trialEnd pointSingle-arm phase II clinical trialCoprimary end pointsExploratory end pointsObjective response ratePIK3CA mutation statusSingle-agent platinumLong-term respondersPlatinum-based chemotherapyIdentification of patientsBRCA1/2 mutation carriersGenomic instability signatureGene expression subtypesP73 gene expressionPlatinum monotherapyMutation carriers
2014
Phase 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
2007
Genetic testing in young women with breast cancer: Results from a web-based survey
Shin J, Gelber S, Garber J, Rosenberg R, Przypyszny M, Winer E, Partridge A. Genetic testing in young women with breast cancer: Results from a web-based survey. Journal Of Clinical Oncology 2007, 25: 21093-21093. DOI: 10.1200/jco.2007.25.18_suppl.21093.Peer-Reviewed Original ResearchBreast cancerOvarian cancerFamily historyGenetic testingYoung womenWeb-based surveyYoung breast cancer survivorsTime of diagnosisBreast cancer survivorsHigh-risk populationMajority of womenFear of recurrenceQuality of lifeCross-sectional surveyLarge web-based surveyBreast cancer diagnosisCancer survivorsBRCA1/2 mutationsAge 40Baseline anxietyNumber of childrenFertility issuesCancerMultivariate modelSignificant financial relationship