2024
Analysis of HER2 expression changes from breast primary to brain metastases and the impact of HER2-low expression on overall survival
Pereslete A, Hughes M, Martin A, Files J, Nguyen K, Buckley L, Patel A, Moore A, Winer E, Dillon D, Li T, Tolaney S, Lin N, Sammons S. Analysis of HER2 expression changes from breast primary to brain metastases and the impact of HER2-low expression on overall survival. Neuro-Oncology 2024, noae163. PMID: 39211994, DOI: 10.1093/neuonc/noae163.Peer-Reviewed Original ResearchHER2-low expressionHER2-lowMetastatic breast cancerHER2-positiveHER2 expressionHER2-0Primary tumorBrain metastasesEstrogen receptorBreast cancerHER2-positive primary tumorsASCO-CAP guidelinesNCI-designated centersMultivariate survival analysisCox proportional hazards modelsAntibody-drug conjugatesProportional hazards modelActive antibody-drug conjugateASCO-CAPHER2 gainHER2 statusInferior survivalOverall survivalIntracranial activityRetrospective analysis
2021
Temporal and spatial topography of cell proliferation in cancer.
Kabraji S, Gaglia G, Argyropoulou D, Dai Y, Wang S, Bergholz J, Coy S, Lin J, Jeselsohn R, Metzger O, Winer E, Dillon D, Zhao J, Sorger P, Santagata S. Temporal and spatial topography of cell proliferation in cancer. Journal Of Clinical Oncology 2021, 39: 3122-3122. DOI: 10.1200/jco.2021.39.15_suppl.3122.Peer-Reviewed Original ResearchCell cycle stateCancer cellsBreast cancerTumor-infiltrating immune cellsDisease-free survivalCell cycle protein expressionCell proliferationDormant cancer cellsCancer cell proliferationQuiescent cancer cellsCycle stateCancer stem cellsSame primary tumorNeoadjuvant therapyProliferative cancer cellsAdjuvant therapyClinical outcomesColorectal cancerPrimary tumorImmune cellsUntreated tumorsDiverse tumor typesUnique tumorProliferation indexProliferative indexGenomic features of rapid versus late relapse in triple negative breast cancer
Zhang Y, Asad S, Weber Z, Tallman D, Nock W, Wyse M, Bey JF, Dean KL, Adams EJ, Stockard S, Singh J, Winer EP, Lin NU, Jiang YZ, Ma D, Wang P, Shi L, Huang W, Shao ZM, Cherian M, Lustberg MB, Ramaswamy B, Sardesai S, VanDeusen J, Williams N, Wesolowski R, Obeng-Gyasi S, Sizemore GM, Sizemore ST, Verschraegen C, Stover DG. Genomic features of rapid versus late relapse in triple negative breast cancer. BMC Cancer 2021, 21: 568. PMID: 34006255, PMCID: PMC8130400, DOI: 10.1186/s12885-021-08320-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkers, TumorChemotherapy, AdjuvantDatasets as TopicDisease-Free SurvivalDNA Copy Number VariationsFemaleFollow-Up StudiesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLogistic ModelsMastectomyMiddle AgedModels, GeneticMutationNeoadjuvant TherapyNeoplasm Recurrence, LocalPrognosisRisk AssessmentTime FactorsTriple Negative Breast NeoplasmsConceptsLate relapseRapid relapseImmune signaturesBreast cancerAnti-tumor CD8 T cellsBackgroundTriple-negative breast cancerTriple-negative breast cancerCD8 T cellsTumor mutation burdenIndependent validation cohortNegative breast cancerFisher's exact testPearson's chi-squared testChi-squared testLogistic regression modelsLuminal signaturePrimary TNBCTNBC subsetImmune subsetsClinical featuresValidation cohortWhole-genome copy numberPrimary tumorM1 macrophagesT cellsTwenty-year risks of breast cancer-specific mortality for stage III breast cancer in the surveillance, epidemiology, and end results registry
Leone JP, Leone BA, Tayob N, Hassett MJ, Leone J, Freedman RA, Tolaney SM, Winer EP, Vallejo CT, Lin NU. Twenty-year risks of breast cancer-specific mortality for stage III breast cancer in the surveillance, epidemiology, and end results registry. Breast Cancer Research And Treatment 2021, 187: 843-852. PMID: 33590387, DOI: 10.1007/s10549-021-06121-x.Peer-Reviewed Original ResearchConceptsRisk of BCSMBreast cancer-specific mortalityStage III breast cancerHR-negative diseaseHR-positive diseaseCancer-specific mortalityBreast cancerLate deathsNodal statusTumor sizeUnknown hormone receptor statusHR-positive tumorsEnd Results registryHormone receptor statusEnd Results (SEER) dataTraditional clinicopathologic factorsCumulative incidence functionGray regressionMethodsUsing SurveillanceAxillary nodesClinicopathologic factorsReceptor statusStage subgroupsPrimary tumorTumor gradeGenomic Characterization of de novo Metastatic Breast Cancer
Garrido-Castro AC, Spurr LF, Hughes ME, Li YY, Cherniack AD, Kumari P, Lloyd MR, Bychkovsky B, Barroso-Sousa R, Di Lascio S, Jain E, Files J, Mohammed-Abreu A, Krevalin M, MacKichan C, Barry WT, Guo H, Xia D, Cerami E, Rollins BJ, MacConaill LE, Lindeman NI, Krop IE, Johnson BE, Wagle N, Winer EP, Dillon DA, Lin NU. Genomic Characterization of de novo Metastatic Breast Cancer. Clinical Cancer Research 2021, 27: 1105-1118. PMID: 33293374, PMCID: PMC7887078, DOI: 10.1158/1078-0432.ccr-20-1720.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerPrimary tumorOverall survivalBreast cancerDe novo metastatic breast cancerNovo metastatic breast cancerDifferential therapeutic sensitivityBetter OSPoor OSShorter OSInitial diagnosisHigh TMBMetastatic tumorsDnMBCCurrent treatmentMutational burdenTreatment selectionMetastatic driversStage IMultiple comparison adjustmentTherapeutic sensitivityTumorsPatientsCancerIntrinsic resistance
2020
Genomic profiling of breast cancer brain metastases reveals targetable alterations.
Kabraji S, Spurr L, Hughes M, Li Y, Leone J, Garrido-Castro A, Barroso-Sousa R, Files J, Kirkner G, Johnson B, Winer E, Cherniack A, Lin N. Genomic profiling of breast cancer brain metastases reveals targetable alterations. Journal Of Clinical Oncology 2020, 38: 2525-2525. DOI: 10.1200/jco.2020.38.15_suppl.2525.Peer-Reviewed Original ResearchBreast cancer brain metastasesTumor mutation burdenCancer brain metastasesBrain metastasesTargetable alterationsGenomic alterationsDana-Farber Cancer InstituteTwo-sided Fisher's exact testPIK3CA/PTENActionable genomic alterationsFisher's exact testNumber alterationsTwo-sided MannWhitney U testPrimary tumorMetastatic tumorsMutation burdenERBB2 amplificationCancer InstituteMultiple comparison correctionCancer-related genesExact testCopy number alterationsGenomic profilingU testPrevalence and mutational determinants of high tumor mutation burden in breast cancer
Barroso-Sousa R, Jain E, Cohen O, Kim D, Buendia-Buendia J, Winer E, Lin N, Tolaney S, Wagle N. Prevalence and mutational determinants of high tumor mutation burden in breast cancer. Annals Of Oncology 2020, 31: 387-394. PMID: 32067680, DOI: 10.1016/j.annonc.2019.11.010.Peer-Reviewed Original ResearchConceptsHigh tumor mutation burdenTumor mutation burdenPD-1 inhibitorsBreast cancerMutation burdenMedian tumor mutation burdenDifferent mutational signaturesPembrolizumab-based therapyMetastatic breast cancerSubset of patientsMut/MbMismatch repair deficiencyGenomic profilesMutational patternsAPOBEC activityGene panel sequencingMultiple tumor typesWhole-exome sequencingDe-identified dataDurable responsesMetastatic tumorsPrimary tumorTumor subtypesPatientsTumor types
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 resistanceBiopsyAssociation 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
Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets
Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, Van Allen EM, Lawrence MS, Horowitz PM, Cibulskis K, Ligon KL, Tabernero J, Seoane J, Martinez-Saez E, Curry WT, Dunn IF, Paek SH, Park SH, McKenna A, Chevalier A, Rosenberg M, Barker FG, Gill CM, Van Hummelen P, Thorner AR, Johnson BE, Hoang MP, Choueiri TK, Signoretti S, Sougnez C, Rabin MS, Lin NU, Winer EP, Stemmer-Rachamimov A, Meyerson M, Garraway L, Gabriel S, Lander ES, Beroukhim R, Batchelor TT, Baselga J, Louis DN, Getz G, Hahn WC. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discovery 2015, 5: 1164-1177. PMID: 26410082, PMCID: PMC4916970, DOI: 10.1158/2159-8290.cd-15-0369.Peer-Reviewed Original ResearchConceptsBrain metastasesPrimary tumorPrimary biopsiesRegional lymph node metastasisLymph node metastasisPI3K/Akt/mTORRegional lymph nodesPotential therapeutic targetPrimary tumor biopsiesPrimary tumor samplesAkt/mTORDistinct genetic alterationsWhole-exome sequencingExtracranial metastasesLymph nodesNode metastasisDismal prognosisActionable alterationsMetastasis sitesInformative alterationsIndividualized therapyTherapeutic targetMetastasisPrimary siteEGFR inhibitors
2010
International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured?
Pagani O, Senkus E, Wood W, Colleoni M, Cufer T, Kyriakides S, Costa A, Winer EP, Cardoso F. International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured? Journal Of The National Cancer Institute 2010, 102: 456-463. PMID: 20220104, PMCID: PMC3298957, DOI: 10.1093/jnci/djq029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBone NeoplasmsBreast NeoplasmsCatheter AblationChemotherapy, AdjuvantClinical Trials as TopicCongresses as TopicConsensus Development Conferences as TopicDose-Response Relationship, DrugEarly Detection of CancerEuropeFemaleGene Expression ProfilingHumansImmunosuppressive AgentsInterdisciplinary CommunicationInternational CooperationLiver NeoplasmsLung NeoplasmsNeoplasm StagingNeoplastic Cells, CirculatingObserver VariationPatient Care TeamPatient SelectionPractice Guidelines as TopicRadiotherapy, AdjuvantSurvival RateConceptsMetastatic breast cancerOligometastatic diseaseBreast cancerMetastatic lesionsPrimary tumorEuropean Breast Cancer ConferenceFirst consensus recommendationsOptimal local treatmentRapid disease controlAvailable therapeutic optionsSubset of patientsLong-term outcomesLarge retrospective seriesDetectable metastatic lesionsAttractive therapeutic strategyChemotherapy optionsSurvival benefitSystemic therapyTreatment guidelinesRegional chemotherapyRetrospective seriesTask ForceLung metastasesTherapeutic optionsPatient population