2020
Assessment of Ki67 in Breast Cancer: Updated Recommendations From the International Ki67 in Breast Cancer Working Group
Nielsen TO, Leung SCY, Rimm DL, Dodson A, Acs B, Badve S, Denkert C, Ellis MJ, Fineberg S, Flowers M, Kreipe HH, Laenkholm AV, Pan H, Penault-Llorca FM, Polley MY, Salgado R, Smith IE, Sugie T, Bartlett JMS, McShane LM, Dowsett M, Hayes DF. Assessment of Ki67 in Breast Cancer: Updated Recommendations From the International Ki67 in Breast Cancer Working Group. Journal Of The National Cancer Institute 2020, 113: 808-819. PMID: 33369635, PMCID: PMC8487652, DOI: 10.1093/jnci/djaa201.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsFemaleHumansImmunohistochemistryKi-67 AntigenPrognosisReceptor, ErbB-2Receptors, EstrogenConceptsBreast cancerClinical utilityKi67 immunohistochemistryInternational Ki67Breast Cancer Working GroupAnalytical validityAssessment of Ki67HER2-negative patientsBreast cancer careCancer Working GroupGroup consensus meetingAdjuvant chemotherapyVisual scoring methodPatient groupCancer careT1-2Prognostic markerPrognosis assessmentPrognosis estimationTreatment decisionsEstrogen receptorHER2 testingConsensus meetingCurrent evidenceClinical validityEstrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update.
Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, Hayes DF, Lakhani SR, Chavez-MacGregor M, Perlmutter J, Perou CM, Regan MM, Rimm DL, Symmans WF, Torlakovic EE, Varella L, Viale G, Weisberg TF, McShane LM, Wolff AC. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. Journal Of Clinical Oncology 2020, 38: 1346-1366. PMID: 31928404, DOI: 10.1200/jco.19.02309.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsFemaleHumansImmunohistochemistryReceptors, EstrogenReceptors, ProgesteroneSystematic Reviews as TopicConceptsProgesterone receptor testingBreast cancerEndocrine therapyReceptor testingExpert panelClinical practice guideline recommendationsMultidisciplinary international expert panelClinical Oncology/CollegeEndocrine therapy benefitPractice guideline recommendationsER-positive cancersBreast cancer guidelinesInvasive breast cancerFuture breast cancerBreast cancer samplesInternational expert panelReporting of casesPgR testingTumor cell nucleiCancer guidelinesGuideline recommendationsGuideline updateDuctal carcinomaER testingLow positives
2018
CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers
Pelekanou V, Villarroel-Espindola F, Schalper KA, Pusztai L, Rimm DL. CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers. Breast Cancer Research 2018, 20: 154. PMID: 30558648, PMCID: PMC6298021, DOI: 10.1186/s13058-018-1076-x.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic AgentsBiomarkers, TumorBreastBreast NeoplasmsDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansMacrophagesMatrix Metalloproteinase 9Middle AgedPatient SelectionPrognosisReceptors, Cell SurfaceReceptors, EstrogenRetrospective StudiesSurvival AnalysisTissue Array AnalysisTumor MicroenvironmentConceptsTumor-associated macrophagesOverall survivalQuantitative immunofluorescenceMacrophage markersBreast cancerHigh expressionPan-macrophage marker CD68Triple-negative breast cancerCD163/CD68Multiplexed quantitative immunofluorescenceImproved overall survivalProtein expressionWorse overall survivalPoor overall survivalMMP-9 protein expressionSubclass of patientsMacrophage-targeted therapiesMatrix metalloproteinase-9Tissue microarray formatMMP-9 proteinBreast tumor microenvironmentModulator of responseParaffin-embedded tissuesBreast cancer biomarkersCohort BMacrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer
Gupta S, Mani NR, Carvajal-Hausdorf DE, Bossuyt V, Ho K, Weidler J, Wong W, Rhees B, Bates M, Rimm DL. Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer. Laboratory Investigation 2018, 98: 1076-1083. PMID: 29858579, PMCID: PMC6119113, DOI: 10.1038/s41374-018-0064-1.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, Intraductal, NoninfiltratingFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryIn Situ Hybridization, FluorescenceParaffin EmbeddingPathology, ClinicalReal-Time Polymerase Chain ReactionReceptor, ErbB-2Receptors, EstrogenReproducibility of ResultsSensitivity and SpecificityTissue FixationConceptsIHC/FISHDCIS cohortRT-qPCRMRNA transcript levelsDuctal carcinoma casesFine needle aspiratesMRNA expression levelsHER2 concordanceER positivityDuctal carcinomaHER2 expressionGeneXpert systemCarcinoma casesInvasive tumorsNeedle biopsyBreast cancerEstrogen receptorClinical ImmunohistochemistryBiopsy areaTumor tissueMRNA expressionTumor areaCohortMRNA levelsMRNA markers
2016
Automated measurement of estrogen receptor in breast cancer: a comparison of fluorescent and chromogenic methods of measurement
Zarrella ER, Coulter M, Welsh AW, Carvajal DE, Schalper KA, Harigopal M, Rimm D, Neumeister V. Automated measurement of estrogen receptor in breast cancer: a comparison of fluorescent and chromogenic methods of measurement. Laboratory Investigation 2016, 96: 1016-1025. PMID: 27348626, PMCID: PMC5008858, DOI: 10.1038/labinvest.2016.73.Peer-Reviewed Original Research
2015
Loss of antigenicity with tissue age in breast cancer
Combs SE, Han G, Mani N, Beruti S, Nerenberg M, Rimm DL. Loss of antigenicity with tissue age in breast cancer. Laboratory Investigation 2015, 96: 264-269. PMID: 26568292, DOI: 10.1038/labinvest.2015.138.Peer-Reviewed Original ResearchConceptsHuman epidermal growth receptor 2Estrogen receptorQuantitative immunofluorescenceProtein expressionSeries of formalinRandom-effects modelHuman breast carcinomaLarge cooperative groupsParaffin-embedded tissuesKi67 expressionBreast carcinomaBreast cancerIndividual patientsTissue microarrayClinical investigationClinical questionsReceptor 2Tumor specimensPositive casesLoss of antigenicityFFPE biospecimensQuantitative protein expressionBiomarkersCooperative groupsPreservation time
2014
In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas
Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, Rimm DL. In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas. Clinical Cancer Research 2014, 20: 2773-2782. PMID: 24647569, DOI: 10.1158/1078-0432.ccr-13-2702.Peer-Reviewed Original ResearchB7-H1 AntigenBreast NeoplasmsCell Line, TumorFemaleFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansIn Situ HybridizationKaplan-Meier EstimateLymphatic MetastasisLymphocytes, Tumor-InfiltratingMiddle AgedMultivariate AnalysisNeoplasm Recurrence, LocalPrognosisReceptor, ErbB-2Receptors, EstrogenRNA, MessengerTissue Array AnalysisA tissue quality index: an intrinsic control for measurement of effects of preanalytical variables on FFPE tissue
Neumeister VM, Parisi F, England AM, Siddiqui S, Anagnostou V, Zarrella E, Vassilakopolou M, Bai Y, Saylor S, Sapino A, Kluger Y, Hicks DG, Bussolati G, Kwei S, Rimm DL. A tissue quality index: an intrinsic control for measurement of effects of preanalytical variables on FFPE tissue. Laboratory Investigation 2014, 94: 467-474. PMID: 24535259, PMCID: PMC4030875, DOI: 10.1038/labinvest.2014.7.Peer-Reviewed Original ResearchConceptsCold ischemic timeIschemic timeQuantitative immunofluorescenceLevel of expressionTissue qualityER expression levelsBreast cancer casesExpression levelsFormalin fixationInformative epitopesValidation cohortCancer casesBreast cohortProtein statusGlobal assessmentPatient samplesTissue cohortPreanalytical variablesEpitope expressionCohortIntrinsic controlMeasurement of effectsQuality IndexFFPE tissuesEpitopes
2013
Quantitative assessment Ki-67 score for prediction of response to neoadjuvant chemotherapy in breast cancer
Brown JR, DiGiovanna MP, Killelea B, Lannin DR, Rimm DL. Quantitative assessment Ki-67 score for prediction of response to neoadjuvant chemotherapy in breast cancer. Laboratory Investigation 2013, 94: 98-106. PMID: 24189270, DOI: 10.1038/labinvest.2013.128.Peer-Reviewed Original ResearchPrediction of Late Disease Recurrence and Extended Adjuvant Letrozole Benefit by the HOXB13/IL17BR Biomarker
Sgroi DC, Carney E, Zarrella E, Steffel L, Binns SN, Finkelstein DM, Szymonifka J, Bhan AK, Shepherd LE, Zhang Y, Schnabel CA, Erlander MG, Ingle JN, Porter P, Muss HB, Pritchard KI, Tu D, Rimm DL, Goss PE. Prediction of Late Disease Recurrence and Extended Adjuvant Letrozole Benefit by the HOXB13/IL17BR Biomarker. Journal Of The National Cancer Institute 2013, 105: 1036-1042. PMID: 23812955, PMCID: PMC3888138, DOI: 10.1093/jnci/djt146.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAromatase InhibitorsBiomarkers, TumorBreast NeoplasmsCase-Control StudiesChemotherapy, AdjuvantDisease-Free SurvivalFemaleHomeodomain ProteinsHumansIncidenceLetrozoleLogistic ModelsMiddle AgedMultivariate AnalysisNeoplasm GradingNeoplasm Recurrence, LocalNeoplasm StagingNitrilesPredictive Value of TestsPrognosisProspective StudiesReceptor, ErbB-2Receptors, EstrogenReceptors, InterleukinReceptors, Interleukin-17Receptors, ProgesteroneRetrospective StudiesReverse Transcriptase Polymerase Chain ReactionTriazolesConceptsExtended letrozole therapyStandard clinicopathological factorsLate disease recurrenceLate recurrenceLetrozole therapyEndocrine therapyDisease recurrenceClinicopathological factorsLymph node-negative breast cancer patientsNode-negative breast cancer patientsExtended adjuvant endocrine therapyMultivariable conditional logistic regressionExtended adjuvant letrozolePlacebo-treated patientsAdjuvant endocrine therapyER-positive patientsBreast cancer patientsPositive breast cancerConditional logistic regressionReverse transcription-polymerase chain reactionCase-control designAdjuvant letrozoleLetrozole treatmentAbsolute riskCancer patients
2012
Quantitative Assessment of Effect of Preanalytic Cold Ischemic Time on Protein Expression in Breast Cancer Tissues
Neumeister VM, Anagnostou V, Siddiqui S, England AM, Zarrella ER, Vassilakopoulou M, Parisi F, Kluger Y, Hicks DG, Rimm DL. Quantitative Assessment of Effect of Preanalytic Cold Ischemic Time on Protein Expression in Breast Cancer Tissues. Journal Of The National Cancer Institute 2012, 104: 1815-1824. PMID: 23090068, PMCID: PMC3514166, DOI: 10.1093/jnci/djs438.Peer-Reviewed Original ResearchMeSH KeywordsA Kinase Anchor ProteinsBiomarkers, TumorBiopsy, Large-Core NeedleBreast NeoplasmsCold IschemiaConfounding Factors, EpidemiologicFalse Negative ReactionsFemaleFixativesFluorescent Antibody TechniqueFormaldehydeGene Expression Regulation, NeoplasticHumansHypoxia-Inducible Factor 1, alpha SubunitKi-67 AntigenMastectomy, SegmentalMatched-Pair AnalysisMinor Histocompatibility AntigensProspective StudiesProto-Oncogene ProteinsReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneResearch DesignTime FactorsConceptsCold ischemic timeIschemic timeBreast cancer tissuesEstrogen receptorCancer tissuesLoss of antigenicityBreast cancer resectionProtein expressionCore needle biopsyCompanion diagnostic testsConditions of hypoxiaFalse-negative resultsBreast cancer biomarkersCancer resectionProgesterone receptorNeedle biopsyRecent guidelinesCold ischemiaBreast cancerTissue microarrayEvidence of lossQuantitative immunofluorescenceDiagnostic testsAntigenicityAQUA methodHypoxia-induced protein CAIX is associated with somatic loss of BRCA1 protein and pathway activity in triple negative breast cancer
Neumeister VM, Sullivan CA, Lindner R, Lezon-Geyda K, Li J, Zavada J, Martel M, Glazer PM, Tuck DP, Rimm DL, Harris L. Hypoxia-induced protein CAIX is associated with somatic loss of BRCA1 protein and pathway activity in triple negative breast cancer. Breast Cancer Research And Treatment 2012, 136: 67-75. PMID: 22976806, DOI: 10.1007/s10549-012-2232-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, NeoplasmBiomarkers, TumorBRCA1 ProteinBreast NeoplasmsCarbonic Anhydrase IXCarbonic AnhydrasesCell HypoxiaFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedMutationNeoplasm StagingReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSignal TransductionConceptsTriple-negative breast cancerCA IX protein expressionNegative breast cancerBreast cancer cohortTNBC cohortProtein expressionBreast cancerCancer cohortCA IXTriple-negative patientsWorse overall survivalBreast cancer patientsTriple-negative phenotypePARP inhibitor therapyUnselected breast cancer cohortGene expression signaturesInhibitor therapyNegative patientsOverall survivalUnselected cohortCancer patientsBRCA1 protein expressionUseful biomarkerPatientsDefective homologous recombination
2011
Breast Cancer Misclassification: A Major Obstacle to Treatment?
Romeo E, Gustavson MD, Rimm DL. Breast Cancer Misclassification: A Major Obstacle to Treatment? Women's Health 2011, 7: 615-618. PMID: 22040201, DOI: 10.2217/whe.11.69.Peer-Reviewed Original ResearchQuantification of Hormone Receptors to Guide Adjuvant Therapy Choice in Early Breast Cancer: Better Methods Required for Improved Utility
Bartlett J, Rea D, Rimm DL. Quantification of Hormone Receptors to Guide Adjuvant Therapy Choice in Early Breast Cancer: Better Methods Required for Improved Utility. Journal Of Clinical Oncology 2011, 29: 3715-3716. PMID: 21810678, DOI: 10.1200/jco.2011.37.3704.Peer-Reviewed Original ResearchTargeting 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 growthStandardization of Estrogen Receptor Measurement in Breast Cancer Suggests False-Negative Results Are a Function of Threshold Intensity Rather Than Percentage of Positive Cells
Welsh AW, Moeder CB, Kumar S, Gershkovich P, Alarid ET, Harigopal M, Haffty BG, Rimm DL. Standardization of Estrogen Receptor Measurement in Breast Cancer Suggests False-Negative Results Are a Function of Threshold Intensity Rather Than Percentage of Positive Cells. Journal Of Clinical Oncology 2011, 29: 2978-2984. PMID: 21709197, PMCID: PMC3157961, DOI: 10.1200/jco.2010.32.9706.Peer-Reviewed Original ResearchConceptsER-positive patientsEstrogen receptorQuantitative immunofluorescenceBreast cancerTissue microarrayPositive cellsIndependent retrospective cohortsEstrogen receptor measurementsAssessment of survivalTMA cohortFalse-negative resultsRetrospective cohortER immunoreactivityTest discordancePrognostic outcomesIndependent cohortReceptor measurementsLimitations of immunohistochemistryPatientsDiscrepant casesCohortIHC methodPathologists' judgmentsDiscrepant resultsStandardized assaysGefitinib or Placebo in Combination with Tamoxifen in Patients with Hormone Receptor–Positive Metastatic Breast Cancer: A Randomized Phase II Study
Osborne CK, Neven P, Dirix LY, Mackey JR, Robert J, Underhill C, Schiff R, Gutierrez C, Migliaccio I, Anagnostou VK, Rimm DL, Magill P, Sellers M. Gefitinib or Placebo in Combination with Tamoxifen in Patients with Hormone Receptor–Positive Metastatic Breast Cancer: A Randomized Phase II Study. Clinical Cancer Research 2011, 17: 1147-1159. PMID: 21220480, PMCID: PMC3074404, DOI: 10.1158/1078-0432.ccr-10-1869.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDrug-Related Side Effects and Adverse ReactionsErbB ReceptorsFemaleGefitinibHumansMiddle AgedNeoplasms, Hormone-DependentPlacebosQuinazolinesReceptor, ErbB-2Receptors, EstrogenSignal TransductionTamoxifenTreatment OutcomeConceptsAdjuvant aromatase inhibitorsMetastatic breast cancerBreast cancerHormone receptor-positive metastatic breast cancerPositive metastatic breast cancerRandomized phase II studyRandomized phase II trialClinical benefit ratePhase II studyPhase II trialProgression-free survivalStratum 1Epidermal growth factor receptor inhibitor gefitinibFurther investigationAdjuvant tamoxifenImproved PFSPFS HRAI therapyII studyII trialMetastatic diseaseAppropriate patientsPredictive biomarkersPrimary tumorTamoxifen resistance
2010
Pre-analytic variables and phospho-specific antibodies: the Achilles heel of immunohistochemistry
Siddiqui S, Rimm DL. Pre-analytic variables and phospho-specific antibodies: the Achilles heel of immunohistochemistry. Breast Cancer Research 2010, 12: 113. PMID: 21176180, PMCID: PMC3046444, DOI: 10.1186/bcr2782.Peer-Reviewed Original ResearchConceptsCold ischemic timePre-analytic variablesIschemic timeCore needle biopsyCompanion diagnostic testingCompanion diagnostic testsBreast cancer researchProgesterone receptorNeedle biopsyBreast cancerEstrogen receptorCritical therapyDiagnostic testingDiagnostic testsClassic markersImmunohistochemistryCancer researchPhospho-specific antibodiesReceptorsMarkersAchilles heelAutomated Analysis of Tissue Microarrays
Dolled-Filhart M, Gustavson M, Camp RL, Rimm DL, Tonkinson JL, Christiansen J. Automated Analysis of Tissue Microarrays. Methods In Molecular Biology 2010, 664: 151-162. PMID: 20690061, DOI: 10.1007/978-1-60761-806-5_15.Peer-Reviewed Original ResearchAnalytic Variability in Immunohistochemistry Biomarker Studies
Anagnostou VK, Welsh AW, Giltnane JM, Siddiqui S, Liceaga C, Gustavson M, Syrigos KN, Reiter JL, Rimm DL. Analytic Variability in Immunohistochemistry Biomarker Studies. Cancer Epidemiology Biomarkers & Prevention 2010, 19: 982-991. PMID: 20332259, PMCID: PMC3891912, DOI: 10.1158/1055-9965.epi-10-0097.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 3Cancer patientsEstrogen receptorWestern blottingBiomarker studiesEpidermal growth factor receptor 1Breast cancer patientsLung cancer patientsEpidermal growth factor receptor 3Growth factor receptor 1Factor receptor 1Growth factor receptor 3Clone 1D5Worse prognosisHigher eGFRPrognostic classificationER antibodyCancer-related biomarkersCutoff pointBT474 cellsSurvival analysisEGFR antibodyReceptor 1Receptor 3Quantitative immunofluorescence