2022
CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression
Zhang M, Liu ZZ, Aoshima K, Cai WL, Sun H, Xu T, Zhang Y, An Y, Chen JF, Chan LH, Aoshima A, Lang SM, Tang Z, Che X, Li Y, Rutter SJ, Bossuyt V, Chen X, Morrow JS, Pusztai L, Rimm DL, Yin M, Yan Q. CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression. Science Translational Medicine 2022, 14: eabf5473. PMID: 35108062, PMCID: PMC9003667, DOI: 10.1126/scitranslmed.abf5473.Peer-Reviewed Original ResearchConceptsBreast cancer metastasisReticuloendotheliosis viral oncogene homolog ACancer metastasisImmune suppressionM2 macrophagesWorse metastasis-free survivalMetastatic breast cancerMetastasis-free survivalV-rel avian reticuloendotheliosis viral oncogene homolog ACancer-related deathPrimary breast tumorsMultiple mouse modelsNF-κB signalingImmunocompetent settingNuclear factor-κB family membersMetastasis-promoting genesDistant metastasisMetastatic sitesPrimary tumorEffective therapyBreast cancerMetastasis treatmentMouse modelBreast tumorsMetastasis
2020
Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition
Gale M, Li Y, Cao J, Liu ZZ, Holmbeck MA, Zhang M, Lang SM, Wu L, Do Carmo M, Gupta S, Aoshima K, DiGiovanna MP, Stern DF, Rimm DL, Shadel GS, Chen X, Yan Q. Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition. Cancer Research 2020, 80: 524-535. PMID: 31690671, PMCID: PMC7002225, DOI: 10.1158/0008-5472.can-18-3985.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBreast NeoplasmsCell ProliferationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHumansMiceMice, Inbred NODMice, SCIDMitochondrial Proton-Translocating ATPasesOligomycinsReceptor, ErbB-2TrastuzumabTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsResistant cellsHER2-Targeted TherapyTrastuzumab-resistant tumorsNew therapeutic strategiesNovel potential targetDrug-free mediumAntibody therapySynthase inhibitionLow doseTherapeutic strategiesTrastuzumabBreast tumorsHER2TherapyAcquired ResistanceTumorsPotential targetMitochondrial respirationCellsSelective dependencyInhibitionMinimal changesNovel vulnerabilitiesATP synthase inhibitionOligomycin A
2018
An international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer
Rimm DL, Leung SCY, McShane LM, Bai Y, Bane AL, Bartlett JMS, Bayani J, Chang MC, Dean M, Denkert C, Enwere EK, Galderisi C, Gholap A, Hugh JC, Jadhav A, Kornaga EN, Laurinavicius A, Levenson R, Lima J, Miller K, Pantanowitz L, Piper T, Ruan J, Srinivasan M, Virk S, Wu Y, Yang H, Hayes DF, Nielsen TO, Dowsett M. An international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer. Modern Pathology 2018, 32: 59-69. PMID: 30143750, DOI: 10.1038/s41379-018-0109-4.Peer-Reviewed Original ResearchConceptsIntraclass correlation coefficientBreast cancerBreast Cancer Working GroupAssessment of Ki67Pre-specified analysisCancer Working GroupInternational multicenter studyMulticenter studySubsequent clinical validationInternational Ki67Biopsy sectionsClinical valueBiomarker Ki67Breast tumorsKi67 immunohistochemistryEvaluation of reproducibilityKi67Clinical validationTumor cellsObserved intraclass correlation coefficientScoring methodCorrelation coefficientKi67 scoringMaximum scoreCancer
2016
Quantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer
Mani NL, Schalper KA, Hatzis C, Saglam O, Tavassoli F, Butler M, Chagpar AB, Pusztai L, Rimm DL. Quantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer. Breast Cancer Research 2016, 18: 78. PMID: 27473061, PMCID: PMC4966732, DOI: 10.1186/s13058-016-0737-x.Peer-Reviewed Original ResearchConceptsIntraclass correlation coefficientQuantitative immunofluorescenceBreast cancerSame cancerSingle biopsyMultiplexed quantitative immunofluorescenceTumor-infiltrating lymphocytesPotential predictive markerPrimary breast carcinomaCytokeratin-positive epithelial cellsCD20-positive lymphocytesCD8 levelsLymphocyte scoreQIF scoresLymphocyte countLymphocyte subpopulationsMultiple biopsiesSubpopulation countsPredictive markerPrognostic informationBreast carcinomaBiopsyB lymphocytesCD3Breast tumors
2014
Preanalytical variables and phosphoepitope expression in FFPE tissue: quantitative epitope assessment after variable cold ischemic time
Vassilakopoulou M, Parisi F, Siddiqui S, England AM, Zarella ER, Anagnostou V, Kluger Y, Hicks DG, Rimm DL, Neumeister VM. Preanalytical variables and phosphoepitope expression in FFPE tissue: quantitative epitope assessment after variable cold ischemic time. Laboratory Investigation 2014, 95: 334-341. PMID: 25418580, DOI: 10.1038/labinvest.2014.139.Peer-Reviewed Original ResearchConceptsCold ischemic timeIschemic timeFormalin fixationCompanion diagnostic testingCancer patientsBreast cancerTissue microarrayPhospho-HSP27Breast tumorsDiagnostic testingQuantitative immunofluorescenceAQUA technologyPreanalytical variablesGene expression profilingLoss of antigenicityTissue samplesReproducible assessmentProtein levelsConfidence intervalsSpecimen collectionExpression levelsPhosphorylation levelsAntigenicityRoutine usageResearch settings
2012
Lin28 regulates HER2 and promotes malignancy through multiple mechanisms
Feng C, Neumeister V, Ma W, Xu J, Lu L, Bordeaux J, Maihle NJ, Rimm DL, Huang Y. Lin28 regulates HER2 and promotes malignancy through multiple mechanisms. Cell Cycle 2012, 11: 2486-2494. PMID: 22713243, DOI: 10.4161/cc.20893.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2HER2 expressionLin28 expressionEpidermal growth factor receptor 2Growth factor receptor 2Primary breast tumorsFactor receptor 2Cancer cell growthMajor therapeutic targetMultiple mechanismsAdvanced human malignanciesClinical outcomesPoor prognosisBreast cancerReceptor 2Therapeutic targetBreast tumorsNovel mechanistic insightsHuman malignanciesLin28 overexpressionReceptor tyrosine kinasesCancerCell proliferationHuman cancersPowerful predictorCytoplasmic Estrogen Receptor in Breast Cancer
Welsh AW, Lannin DR, Young GS, Sherman ME, Figueroa JD, Henry NL, Ryden L, Kim C, Love RR, Schiff R, Rimm DL. Cytoplasmic Estrogen Receptor in Breast Cancer. Clinical Cancer Research 2012, 18: 118-126. PMID: 21980134, PMCID: PMC3263348, DOI: 10.1158/1078-0432.ccr-11-1236.Peer-Reviewed Original ResearchConceptsEstrogen receptorCytoplasmic stainingCytoplasmic ERCytoplasmic estrogen receptorSpecific cytoplasmic stainingCell line seriesHuman breast tumorsQuantitative immunofluorescent analysisRoutine clinical valueRetrospective cohortTamoxifen resistanceBreast cancerLower incidencePreclinical modelsClinical valueTissue microarrayPatient controlsBreast tumorsNumber of casesClinical specimensMultiple antibodiesWestern blotAverage incidenceAntibodiesCohort
2011
Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer
Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, Rimm DL, Liu XS, Brown M. Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer. Cancer Cell 2011, 20: 119-131. PMID: 21741601, PMCID: PMC3180861, DOI: 10.1016/j.ccr.2011.05.026.Peer-Reviewed Original ResearchMeSH KeywordsAndrogensAnilidesAnimalsBeta CateninBreast NeoplasmsCell Line, TumorCell ProliferationDihydrotestosteroneFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHepatocyte Nuclear Factor 3-alphaHumansMiceNitrilesReceptor, ErbB-2Receptors, AndrogenReceptors, EstrogenSignal TransductionTosyl CompoundsTranscriptional ActivationUp-RegulationWnt ProteinsXenograft Model Antitumor AssaysConceptsAndrogen receptorBreast cancerEstrogen receptorER-/HER2Estrogen receptor-negative breast cancerReceptor-negative breast cancerBreast cancer growthER- breast tumorsPotential therapeutic approachTumor cell growthAndrogen-regulated gene expressionEndocrine therapyER statusTherapeutic approachesAR cistromeBreast tumorsCancer growthDirect transcriptional inductionCancerHER2Ligand-dependent activationReceptorsSpecific targetingTumorsCell growthOptimal tumor sampling for immunostaining of biomarkers in breast carcinoma
Tolles J, Bai Y, Baquero M, Harris LN, Rimm DL, Molinaro AM. Optimal tumor sampling for immunostaining of biomarkers in breast carcinoma. Breast Cancer Research 2011, 13: r51. PMID: 21592345, PMCID: PMC3218938, DOI: 10.1186/bcr2882.Peer-Reviewed Original ResearchConceptsWhole tissue sectionsBreast carcinomaEstrogen receptorBiomarker expressionTumor biomarker expressionAmount of tumorTissue sectionsEvidence-based standardsHeterogeneous markersTherapeutic responseHER-2Optimal tumorBreast biopsyBreast tumorsClinical implicationsMAP-tauQuantitative immunofluorescenceClinical useLevel of expressionCarcinomaImmunostaining assaysBiomarkersTumorsTissue samplesBiomarker heterogeneity
2009
Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features
Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, Rimm DL, Wong H, Rodriguez A, Herschkowitz JI, Fan C, Zhang X, He X, Pavlick A, Gutierrez MC, Renshaw L, Larionov AA, Faratian D, Hilsenbeck SG, Perou CM, Lewis MT, Rosen JM, Chang JC. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 13820-13825. PMID: 19666588, PMCID: PMC2720409, DOI: 10.1073/pnas.0905718106.Peer-Reviewed Original ResearchConceptsBreast cancerConventional treatmentHigh tumor-initiating potentialResidual breast cancerBreast cancer patientsCell surface antigen profileLong-term survivalHuman breast tumorsBreast cancer cellsTumor-initiating cellsTumor-initiating potentialEndocrine therapyGene expression signaturesCancer patientsTumor cell populationClinical significanceMolecular subtypesTherapeutic strategiesMesenchymal markersMetalloproteinase-2Breast tumorsSubpopulation of cellsAntigen profileMesenchymal featuresTumor tissue
2008
Expression of Aurora A (but Not Aurora B) Is Predictive of Survival in Breast Cancer
Nadler Y, Camp RL, Schwartz C, Rimm DL, Kluger HM, Kluger Y. Expression of Aurora A (but Not Aurora B) Is Predictive of Survival in Breast Cancer. Clinical Cancer Research 2008, 14: 4455-4462. PMID: 18628459, PMCID: PMC5849429, DOI: 10.1158/1078-0432.ccr-07-5268.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAurora Kinase BAurora KinasesBiomarkers, TumorBlotting, WesternBreast NeoplasmsCell Line, TumorFemaleHistory, 17th CenturyHumansImage Processing, Computer-AssistedImmunohistochemistryKaplan-Meier EstimatePrognosisProtein Serine-Threonine KinasesTissue Array AnalysisConceptsBreast cancerB expressionAurora B expressionBreast tumorsHigh AuroraEarly-stage breast cancerHER-2/neuProgesterone receptor expressionSubset of patientsPopulation of patientsIndependent prognostic markerHigh nuclear gradePrimary breast tumorsCy5-conjugated antibodiesPathologic variablesPrognostic roleMultivariable analysisProspective studyNuclear gradePrognostic markerReceptor expressionClinical developmentPatientsPredictive roleCancerExpression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer
Nadler Y, Camp RL, Giltnane JM, Moeder C, Rimm DL, Kluger HM, Kluger Y. Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer. Breast Cancer Research 2008, 10: r35. PMID: 18430249, PMCID: PMC2397537, DOI: 10.1186/bcr1998.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsDNA-Binding ProteinsDrug Resistance, NeoplasmFemaleFluorescent Antibody TechniqueFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateLymphatic MetastasisMiddle AgedPredictive Value of TestsPrognosisProportional Hazards ModelsProtein Array AnalysisProto-Oncogene Proteins c-bcl-2Receptors, EstrogenReceptors, ProgesteroneTranscription FactorsTreatment OutcomeConceptsNode-positive subsetHER2/neuProgesterone receptorBreast cancerEstrogen receptorBcl-2 expressionBAG-1 expressionImproved survivalBcl-2Anti-apoptotic mediator Bcl-2Breast tumorsSteroid receptor positivitySubset of patientsBAG-1Antihormonal therapyFavorable prognosisReceptor positivityMultivariable analysisPathological variablesEntire cohortPrognostic valuePrognostic markerImproved outcomesLarge cohortClinical development
2003
Quantitative analysis of breast cancer tissue microarrays shows that both high and normal levels of HER2 expression are associated with poor outcome.
Camp RL, Dolled-Filhart M, King BL, Rimm DL. Quantitative analysis of breast cancer tissue microarrays shows that both high and normal levels of HER2 expression are associated with poor outcome. Cancer Research 2003, 63: 1445-8. PMID: 12670887.Peer-Reviewed Original ResearchConceptsHER2 expressionLow-level HER2 expressionHER2/neu expressionHER2-overexpressing tumorsDisease-related survivalTissue microarray cohortNormal breast epitheliumBreast cancer tissuesMicroarray cohortPoor outcomeNeu expressionWorse outcomesBreast cancerImmunohistochemical stainsBreast epitheliumNormal epitheliumCancer tissuesBreast tumorsTumorsNormal levelsExpression levelsHER2AQUA analysisDetectable levelsLow group