2021
Association of 17q22 Amplicon Via Cell-Free DNA With Platinum Chemotherapy Response in Metastatic Triple-Negative Breast Cancer
Collier KA, Asad S, Tallman D, Jenison J, Rajkovic A, Mardis ER, Parsons HA, Tolaney SM, Winer EP, Lin NU, Ha G, Adalsteinsson VA, Stover DG. Association of 17q22 Amplicon Via Cell-Free DNA With Platinum Chemotherapy Response in Metastatic Triple-Negative Breast Cancer. JCO Precision Oncology 2021, 5: po.21.00104. PMID: 34849445, PMCID: PMC8624042, DOI: 10.1200/po.21.00104.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerProgression-free survivalTriple-negative breast cancerPlatinum chemotherapyCancer Genome AtlasBreast cancerBreast Cancer International Consortium data setLonger median progression-free survivalMedian progression-free survivalPlatinum-based chemotherapy regimenSomatic copy number alterationsCopy number alterationsCox proportional hazards modelPlatinum chemotherapy responseTriple negative breast cancer tumorsSpecific somatic copy number alterationsGenome AtlasBreast Cancer International ConsortiumProportional hazards modelBreast cancer tumorsWarrants further investigationCell-free DNAEvaluable patientsChemotherapy regimenMetastatic settingUpdated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB).
Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey L, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Zhang C, Winer E. Updated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB). Journal Of Clinical Oncology 2021, 39: 1043-1043. DOI: 10.1200/jco.2021.39.15_suppl.1043.Peer-Reviewed Original ResearchMetastatic breast cancerBrain metastasesOverall survivalTyrosine kinase inhibitorsBreast cancerPlacebo armAnalysis of OSOral tyrosine kinase inhibitorECOG performance statusPlacebo-controlled trialTotal study populationKaplan-Meier timeHER2CLIMB trialMeaningful prolongationMetastatic HER2Study medicationTolerability assessmentsMetastatic settingAdverse eventsDose modificationHazard ratioLast patientPerformance statusDisease progressionStudy population
2019
Ribociclib Plus Trastuzumab in Advanced HER2-Positive Breast Cancer: Results of a Phase 1b/2 Trial
Goel S, Pernas S, Tan-Wasielewski Z, Barry WT, Bardia A, Rees R, Andrews C, Tahara RK, Trippa L, Mayer EL, Winer EP, Spring LM, Tolaney SM. Ribociclib Plus Trastuzumab in Advanced HER2-Positive Breast Cancer: Results of a Phase 1b/2 Trial. Clinical Breast Cancer 2019, 19: 399-404. PMID: 31235441, DOI: 10.1016/j.clbc.2019.05.010.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerAdvanced HER2-positive breast cancerProgression-free survivalBreast cancerAdverse eventsObjective responseGrade 3 adverse eventsGrade 4/5 adverse eventsHormone receptor-positive diseaseMedian progression-free survivalAnti-HER2 combinationClinical benefit rateHER2-negative diseasePhase 1b/2 studyPhase 1b/2 trialPrior therapy linesReceptor-positive diseaseAnti-HER2 therapyNew safety concernsCyclin-dependent kinase 4Stable diseaseExpansion cohortMetastatic settingPrior linesQTc prolongationCharacterization of mutational processes in ER+ metastatic breast cancer.
Buendia-Buendia J, Cohen O, Kim D, Jain E, Winer E, Lin N, Wagle N. Characterization of mutational processes in ER+ metastatic breast cancer. Journal Of Clinical Oncology 2019, 37: 1019-1019. DOI: 10.1200/jco.2019.37.15_suppl.1019.Peer-Reviewed Original ResearchMetastatic breast cancerEarly-stage breast cancerSubset of patientsStage breast cancerWhole-exome sequencingBreast cancerManagement of MBCMutational signaturesMBC samplesMetastatic tumor biopsiesNormal aging processEndocrine therapyMetastatic settingCancer Genome AtlasClinical featuresClinical trialsDisease progressionTumor biopsiesPrimary biopsiesMutational burdenTumor evolutionBreast tumorsMBC tumorsCancerTumor samples
2018
Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to estrogen receptor–directed therapies
Nayar U, Cohen O, Kapstad C, Cuoco MS, Waks AG, Wander SA, Painter C, Freeman S, Persky NS, Marini L, Helvie K, Oliver N, Rozenblatt-Rosen O, Ma CX, Regev A, Winer EP, Lin NU, Wagle N. Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to estrogen receptor–directed therapies. Nature Genetics 2018, 51: 207-216. PMID: 30531871, DOI: 10.1038/s41588-018-0287-5.Peer-Reviewed Original ResearchConceptsHER2 mutationsEstrogen receptorBreast cancerClinical resistance mechanismsMainstay of treatmentMetastatic breast cancerReceptor-directed therapyCDK6 inhibitor palbociclibPre-existing mutationsMetastatic settingEstrogen independenceInhibitor palbociclibPrimary tumorMetastatic biopsiesInhibitor neratinibTherapyPatientsER mutationsCancerTamoxifenResistance mechanismsDistinct mechanismsMutationsConfer resistanceBiopsyUnraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer
Kuang Y, Siddiqui B, Hu J, Pun M, Cornwell M, Buchwalter G, Hughes ME, Wagle N, Kirschmeier P, Jänne PA, Paweletz CP, Lin NU, Krop IE, Barry WT, Winer EP, Brown M, Jeselsohn R. Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer. Npj Breast Cancer 2018, 4: 22. PMID: 30083595, PMCID: PMC6072793, DOI: 10.1038/s41523-018-0075-5.Peer-Reviewed Original ResearchMetastatic breast cancerESR1 mutationsBreast cancerMetastatic settingClinicopathological featuresPIK3CA mutationsAromatase inhibitorsER-positive metastatic breast cancerDetailed clinical dataSpecific systemic treatmentMetastatic treatmentDistant recurrenceMetastatic diseaseSystemic treatmentPrimary diseaseEndocrine resistanceCDK4/6 inhibitorsPathological featuresFulvestrant treatmentClinical dataPrior treatmentSignificant associationPatientsCancerPrevalenceAssociation of Cell-Free DNA Tumor Fraction and Somatic Copy Number Alterations With Survival in Metastatic Triple-Negative Breast Cancer
Stover DG, Parsons HA, Ha G, Freeman SS, Barry WT, Guo H, Choudhury AD, Gydush G, Reed SC, Rhoades J, Rotem D, Hughes ME, Dillon DA, Partridge AH, Wagle N, Krop IE, Getz G, Golub TR, Love JC, Winer EP, Tolaney SM, Lin NU, Adalsteinsson VA. Association of Cell-Free DNA Tumor Fraction and Somatic Copy Number Alterations With Survival in Metastatic Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2018, 36: jco.2017.76.003. PMID: 29298117, PMCID: PMC5815405, DOI: 10.1200/jco.2017.76.0033.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerPrimary triple-negative breast cancerTumor fractionSomatic copy number alterationsCell-free DNABreast cancerSingle tertiary care institutionCopy number alterationsRetrospective cohort studySpecific somatic copy number alterationsTertiary care institutionNovel therapeutic approachesNumber alterationsCfDNA tumor fractionMetastatic survivalPrior chemotherapyTNBC cohortMetastatic settingCohort studyOverall survivalCancer Genome AtlasClinicopathologic factorsWorse survivalPrimary tumor
2015
Tailoring adjuvant chemotherapy regimens for patients with triple negative breast cancer
Stover DG, Winer EP. Tailoring adjuvant chemotherapy regimens for patients with triple negative breast cancer. The Breast 2015, 24: s132-s135. PMID: 26255198, DOI: 10.1016/j.breast.2015.07.032.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBreast cancerAdjuvant chemotherapyHigh-risk triple negative breast cancerLong-term outcome dataAnthracycline-taxane combinationsBRCA mutation carriersStandard of careNegative breast cancerPoor prognosis subtypeAdjuvant settingStandard regimensToxic regimensMetastatic settingCytotoxic chemotherapySystemic therapyImmune infiltratesTumor characteristicsMutation carriersOutcome dataWarrants further considerationStage ISpecific subgroupsChemotherapyCancerPhase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer
Tolaney SM, Tan S, Guo H, Barry W, Van Allen E, Wagle N, Brock J, Larrabee K, Paweletz C, Ivanova E, Janne P, Overmoyer B, Wright JJ, Shapiro GI, Winer EP, Krop IE. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer. Investigational New Drugs 2015, 33: 1108-1114. PMID: 26123926, PMCID: PMC4608248, DOI: 10.1007/s10637-015-0269-8.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerPhase 2 studyProgression-free survivalBreast cancerPartial responseSingle-arm phase 2 studyResults 22 patientsPhase II studyDaily oral dosingOverall response rateRecent preclinical dataMechanism of actionTivantinib monotherapyMetastatic settingAdverse eventsII studyMethods PatientsPrior linesPreclinical dataOral dosingTivantinibPatientsMET expressionResponse rate
2013
Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era
Olson EM, Najita JS, Sohl J, Arnaout A, Burstein HJ, Winer EP, Lin NU. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. The Breast 2013, 22: 525-531. PMID: 23352568, PMCID: PMC3713786, DOI: 10.1016/j.breast.2012.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCentral Nervous System NeoplasmsCohort StudiesDisease-Free SurvivalFemaleFollow-Up StudiesHumansKaplan-Meier EstimateLiver NeoplasmsLung NeoplasmsMiddle AgedPractice Patterns, Physicians'PrognosisProportional Hazards ModelsReceptor, ErbB-2Retrospective StudiesTrastuzumabTreatment OutcomeConceptsHER2-positive metastatic breast cancerMetastatic breast cancerMedian overall survivalTrastuzumab-based therapyOverall survivalHazard ratioMedian durationBreast cancerCox proportional hazards modelCentral nervous system diseasePost-trastuzumab eraTreatment practice patternsHER2-positive patientsKaplan-Meier methodologyLog-rank testPatterns of careLine of treatmentNervous system diseasesProportional hazards modelTime of deathCNS metastasesCNS progressionMetastatic settingFirst recurrenceShorter OS
2012
Human epidermal growth factor receptor-2-positive breast cancer: does estrogen receptor status define two distinct subtypes?
Vaz-Luis I, Winer EP, Lin NU. Human epidermal growth factor receptor-2-positive breast cancer: does estrogen receptor status define two distinct subtypes? Annals Of Oncology 2012, 24: 283-291. PMID: 23022997, PMCID: PMC3551479, DOI: 10.1093/annonc/mds286.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerHER2-positive diseaseEstrogen receptor statusBreast cancerReceptor statusClinical outcomesEpidermal growth factor receptor 2 overexpressionHuman epidermal growth factor receptor 2 (HER2) overexpressionDistinct subtypesFuture clinical trialsEfficacy of therapyMetastatic settingNeoadjuvant therapyMetastatic diseaseER statusSurvival outcomesClinical trialsPatterns of disseminationTherapyCancerDiseaseSubstantial minorityOutcomesSubtypesHeterogeneous entity
2009
Quality of Life of Early Stage Breast Cancer Patients 65 Years Old or Older Randomized to Standard Chemotherapy or Capecitabine: A Cancer and Leukemia Group B Study (CALGB 49907).
Kornblith A, Archer L, Lan L, Kimmick G, Partridge A, Casey R, Bennett S, Hudis C, Winer E, Cohen H, Muss H. Quality of Life of Early Stage Breast Cancer Patients 65 Years Old or Older Randomized to Standard Chemotherapy or Capecitabine: A Cancer and Leukemia Group B Study (CALGB 49907). Cancer Research 2009, 69: 5035-5035. DOI: 10.1158/0008-5472.sabcs-09-5035.Peer-Reviewed Original ResearchEnd of treatmentSimilar clinical outcomesStandard chemotherapyClinical outcomesCapecitabine patientsQoL resultsTreatment recommendationsLess toxicityLeukemia Group B StudyRandomized phase III trialBetter overall QoLPatients 65 yearsStandard chemotherapy armOlder cancer patientsPhase III trialsWorse clinical outcomesSystemic side effectsBetter body imageQuality of lifeCapecitabine armChemotherapy armLess constipationWorse diarrheaCapecitabine treatmentMetastatic settingTolerability and efficacy of 500 mg fulvestrant in postmenopausal women with estrogen receptor (ER)+ advanced breast cancer
Come S, Parker L, Wulf G, Kuter I, Ryan P, Tkaczuk K, Borges V, Kasper H, Gelman R, Winer E. Tolerability and efficacy of 500 mg fulvestrant in postmenopausal women with estrogen receptor (ER)+ advanced breast cancer. Journal Of Clinical Oncology 2009, 27: 1050-1050. DOI: 10.1200/jco.2009.27.15_suppl.1050.Peer-Reviewed Original ResearchClinical benefit rateStable diseasePartial responseComplete responseEstrogen receptorEndocrine therapyMedian timeBreast cancerEvaluable metastatic breast cancerFirst-line metastatic settingInjection site discomfortAdjuvant endocrine therapyAdjuvant endocrine treatmentPhase II studyTreatment-related toxicityMetastatic breast cancerAdvanced diseaseEndocrine treatmentMetastatic settingPostmenopausal patientsPrimary endpointRECIST criteriaVisceral metastasesII studyPostmenopausal women
2008
Racial Differences in Clinical Outcomes From Metastatic Breast Cancer: A Pooled Analysis of CALGB 9342 and 9840—Cancer and Leukemia Group B
Polite BN, Cirrincione C, Fleming GF, Berry DA, Seidman A, Muss H, Norton L, Shapiro C, Bakri K, Marcom K, Lake D, Schwartz JH, Hudis C, Winer EP. Racial Differences in Clinical Outcomes From Metastatic Breast Cancer: A Pooled Analysis of CALGB 9342 and 9840—Cancer and Leukemia Group B. Journal Of Clinical Oncology 2008, 26: 2659-2665. PMID: 18509177, PMCID: PMC4830463, DOI: 10.1200/jco.2007.13.9782.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerHazard of deathTreatment failureBreast cancerOverall survivalClinical outcomesLeukemia Group B trialAfrican AmericansLeukemia Group BMedian overall survivalTreatment-related toxicityObserved survival differencesTime of presentationAfrican American patientsRacial differencesOverall responseAfrican American womenLarge cooperative groupsMetastatic settingProtocol treatmentPrognostic factorsStudy cohortSubsequent therapyShorter survivalPooled analysis
2006
HER2 testing in breast cancer: NCCN Task Force report and recommendations.
Carlson RW, Moench SJ, Hammond ME, Perez EA, Burstein HJ, Allred DC, Vogel CL, Goldstein LJ, Somlo G, Gradishar WJ, Hudis CA, Jahanzeb M, Stark A, Wolff AC, Press MF, Winer EP, Paik S, Ljung BM, _ _. HER2 testing in breast cancer: NCCN Task Force report and recommendations. Journal Of The National Comprehensive Cancer Network 2006, 4 Suppl 3: s1-22; quiz s23-4. PMID: 16813731, DOI: 10.6004/jnccn.2006.2003.Peer-Reviewed Original ResearchConceptsBreast cancerHER2 testingHER2 statusIHC scoreMetastatic settingCopies/cellPredictive factorsHER2 expressionTask force membersEvidence-based consensus approachInvasive breast cancerCancer patient evaluationTask ForceBreast cancer panelGene amplificationBreast cancer tumorsAreas of controversyAdjuvant settingHER2 biologyMedical oncologyPatient evaluationClinical trialsMultidisciplinary panelSurgical oncologyHER2
1998
Oral 5-FU analogues in the treatment of breast cancer.
Bunnell CA, Winer EP. Oral 5-FU analogues in the treatment of breast cancer. Oncology 1998, 12: 39-43. PMID: 9830624.Peer-Reviewed Original ResearchConceptsPhase II trialBreast cancer patientsBreast cancerII trialCancer patientsResponse rateOpen-label phase II trialRandomized phase II studyCombination of UFTHand-foot syndromePartial response ratePhase II studyTreatment-related toxicityAdvanced breast cancerMetastatic breast cancerOverall response rateTreatment of patientsPreliminary response dataAnthracycline useCommon toxicitiesSalvage therapyMetastatic settingII studyTherapeutic armamentariumGrade 3