2023
Classification of Breast Cancer According to ERBB2 Immunohistochemistry Scores
Robbins C, Fernandez A, Rimm D. Classification of Breast Cancer According to ERBB2 Immunohistochemistry Scores. JAMA Oncology 2023, 9: 1298-1299. PMID: 37498606, DOI: 10.1001/jamaoncol.2023.2635.Commentaries, Editorials and LettersMulti-institutional Assessment of Pathologist Scoring HER2 Immunohistochemistry
Robbins C, Fernandez A, Han G, Wong S, Harigopal M, Podoll M, Singh K, Ly A, Kuba M, Wen H, Sanders M, Brock J, Wei S, Fadare O, Hanley K, Jorns J, Snir O, Yoon E, Rabe K, Soong T, Reisenbichler E, Rimm D. Multi-institutional Assessment of Pathologist Scoring HER2 Immunohistochemistry. Modern Pathology 2023, 36: 100032. PMID: 36788069, PMCID: PMC10278086, DOI: 10.1016/j.modpat.2022.100032.Peer-Reviewed Original ResearchConceptsOverall percent agreementHuman epidermal growth factor 2HER2 IHCReal-world settingEpidermal growth factor 2HER2-negative statusBreast cancer biopsiesCompanion diagnostic testsMulti-institutional assessmentGrowth factor 2Breast cancerImmunohistochemistry assaysCancer biopsiesHER2 immunohistochemistryPathologist concordanceIHCClinical standardsPercent agreementDiagnostic testsSubstantial discordanceERBB2 geneInterrater reliabilityPathologistsFactor 2Concordance
2022
Quantitative measurement of HER2 expression to subclassify ERBB2 unamplified breast cancer.
Moutafi M, Robbins C, Yaghoobi V, Fernandez A, Martinez-Morilla S, Xirou V, Bai Y, Song Y, Gaule P, Krueger J, Bloom K, Hill S, Liebler D, Fulton R, Rimm D. Quantitative measurement of HER2 expression to subclassify ERBB2 unamplified breast cancer. Laboratory Investigation 2022, 102: 1101-1108. PMID: 36775350, DOI: 10.1038/s41374-022-00804-9.Peer-Reviewed Original ResearchConceptsHER2 expressionBreast cancerAttomol/HER2 proteinBreast cancer patientsBreast cancer casesOptimal patient careLevels of HER2Trastuzumab deruxtecanT-DXdCancer patientsLow HER2Cancer casesConventional assaysHER2Patient careAntibody concentrationsQuantitative immunofluorescenceAntibody drugsCancerCell linesAssaysExpressionHER2 detectionLower rangeExamination of Low ERBB2 Protein Expression in Breast Cancer Tissue
Fernandez AI, Liu M, Bellizzi A, Brock J, Fadare O, Hanley K, Harigopal M, Jorns JM, Kuba MG, Ly A, Podoll M, Rabe K, Sanders MA, Singh K, Snir OL, Soong TR, Wei S, Wen H, Wong S, Yoon E, Pusztai L, Reisenbichler E, Rimm DL. Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue. JAMA Oncology 2022, 8: 1-4. PMID: 35113160, PMCID: PMC8814969, DOI: 10.1001/jamaoncol.2021.7239.Peer-Reviewed Original ResearchMeSH KeywordsBreastBreast NeoplasmsFemaleHumansImmunohistochemistryIn Situ Hybridization, FluorescenceReceptor, ErbB-2ConceptsBreast cancer biopsiesT-DXdCancer biopsiesLarge randomized clinical trialsRandomized clinical trialsERBB2 protein expressionCentral pathology laboratoryBreast cancer tissuesAmerican Pathologists surveysStudy of concordanceTrastuzumab deruxtecanERBB2 positivityPatient populationClinical trialsScore 0Breast cancerImmunohistochemistry scoreCancer tissuesIHC assaysPatientsPathology laboratoryProtein expressionBiopsyIHCConcordance
2021
What if the future of HER2‐positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study
Pizzamiglio S, Cosentino G, Ciniselli CM, De Cecco L, Cataldo A, Plantamura I, Triulzi T, El‐abed S, Wang Y, Bajji M, Nuciforo P, Huober J, Ellard SL, Rimm DL, Gombos A, Daidone MG, Verderio P, Tagliabue E, Di Cosimo S, Iorio MV. What if the future of HER2‐positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study. Cancer Medicine 2021, 11: 332-339. PMID: 34921525, PMCID: PMC8729061, DOI: 10.1002/cam4.4449.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancer patientsEvent-free survivalBreast cancer patientsNeoadjuvant therapyCancer patientsPathological complete response rateSingle-agent trastuzumabTwo-miRNA signatureComplete response rateDifferential clinical outcomesPredictive miRNA signatureTrastuzumab armBaseline biopsiesClinical outcomesPathological variablesPrognostic valueUnivariate analysisAgent trastuzumabPrognostic signatureResponse ratePatientsTissue miRNAsMiRNA expression profilesMiRNA signatureMultivariate modelDeep learning trained on hematoxylin and eosin tumor region of Interest predicts HER2 status and trastuzumab treatment response in HER2+ breast cancer
Farahmand S, Fernandez AI, Ahmed FS, Rimm DL, Chuang JH, Reisenbichler E, Zarringhalam K. Deep learning trained on hematoxylin and eosin tumor region of Interest predicts HER2 status and trastuzumab treatment response in HER2+ breast cancer. Modern Pathology 2021, 35: 44-51. PMID: 34493825, PMCID: PMC10221954, DOI: 10.1038/s41379-021-00911-w.Peer-Reviewed Original ResearchConceptsHER2 statusBreast cancerTreatment responseHER2-positive breast cancerAnti-HER2 agentsPre-treatment samplesNeoadjuvant chemotherapyTrastuzumab therapyClinical outcomesClinical evaluationProtein immunohistochemistryHER2 amplificationTrastuzumab responseTumor stainTreatment selectionTCGA testPathology teamTumor regionCancer featuresCancerPatientsHER2Current standardImmunohistochemistryHematoxylinAlpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer
Vathiotis IA, Moutafi MK, Divakar P, Aung TN, Qing T, Fernandez A, Yaghoobi V, El-Abed S, Wang Y, Guillaume S, Nuciforo P, Huober J, Di Cosimo S, Kim SB, Harbeck N, Gomez H, Shafi S, Syrigos KN, Fountzilas G, Sotiriou C, Pusztai L, Warren S, Rimm DL. Alpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer. Clinical Cancer Research 2021, 27: 6156-6163. PMID: 34465600, PMCID: PMC8595766, DOI: 10.1158/1078-0432.ccr-21-2103.Peer-Reviewed Original ResearchConceptsDisease-free survivalHER2-positive breast cancerShorter disease-free survivalBreast cancerQuantitative immunofluorescenceEarly-stage HER2-positive breast cancerAlpha-smooth muscle actin expressionAlpha-smooth muscle actinProgesterone receptor statusHigh α-SMA expressionDigital Spatial ProfilerΑ-SMA expressionPromising candidate biomarkerCompanion diagnostic testsMuscle actin expressionDigital spatial profilingCohort validationNeoadjuvant lapatinibAdjuvant trastuzumabReceptor statusClinical trialsUnivariate analysisEstrogen receptorMAIN OUTCOMEΑ-SMA
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 validityAcquired 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
Macrodissection 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
2017
High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence
Wasserman BE, Carvajal-Hausdorf DE, Ho K, Wong W, Wu N, Chu VC, Lai EW, Weidler JM, Bates M, Neumeister V, Rimm DL. High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence. Laboratory Investigation 2017, 97: 1521-1526. PMID: 28892092, PMCID: PMC5711560, DOI: 10.1038/labinvest.2017.93.Peer-Reviewed Original ResearchConceptsInvasive breast cancerBreast cancerQuantitative immunofluorescenceRT-qPCRFormalin-fixed paraffin-embedded tissue blocksRT-qPCR assaysEquivocal categoryReal-time quantitative reverse transcription polymerase chain reactionHER2 receptor statusQuantitative reverse transcription polymerase chain reactionParaffin-embedded tissue blocksReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionIHC/FISHMRNA measurementsAssessment of HER2Low-resource settingsReceptor statusPolymerase chain reactionPathology reportsCT cutsSingle-use cartridgeResource settingsHER2 mRNATissue blocksErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC
Alvarado D, Ligon GF, Lillquist JS, Seibel SB, Wallweber G, Neumeister VM, Rimm DL, McMahon G, LaVallee TM. ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC. PLOS ONE 2017, 12: e0181356. PMID: 28723928, PMCID: PMC5517012, DOI: 10.1371/journal.pone.0181356.Peer-Reviewed Original ResearchConceptsNeuregulin-1NRG1 expressionErbB3 activationNeck squamous cell carcinomaSquamous cell carcinomaEnhanced anti-tumor activitySubset of HNSCCUnmet medical needHNSCC cell linesHNSCC patient samplesAnti-tumor activityGrowth factor αLigand neuregulin-1Cell carcinomaEGFR/ErbB familyHNSCC modelsCetuximab treatmentErbB receptor inhibitionReceptor inhibitionReceptor levelsRespective signaling pathwaysSolid tumorsTumor typesHNSCCPotential biomarkersCalcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival
Moore LM, England A, Ehrlich BE, Rimm DL. Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival. Molecular Cancer Research 2017, 15: 942-952. PMID: 28275088, PMCID: PMC5500411, DOI: 10.1158/1541-7786.mcr-16-0408.Peer-Reviewed Original ResearchConceptsBreast cancer cellsNCS-1Breast cancer patient cohortsNCS-1 expressionLymph node statusCancer cellsShorter survival rateIndependent breast cancer cohortsCancer patient cohortsBreast cancer cohortMB-231 breast cancer cellsPaclitaxel-induced cell deathAggressive tumor phenotypeNeuronal model systemClinical outcomesClinicopathologic featuresNeuronal calcium sensor-1Node statusPatient cohortProgesterone receptorWorse outcomesBreast cancerCalcium-binding proteinsCancer cohortEstrogen receptorObjective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance
Carvajal-Hausdorf DE, Schalper KA, Bai Y, Black J, Santin AD, Rimm DL. Objective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance. Gynecologic Oncology 2017, 145: 154-158. PMID: 28196634, PMCID: PMC5941302, DOI: 10.1016/j.ygyno.2017.02.002.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAfatinibAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCohort StudiesExtracellular SpaceFemaleFluorescent Antibody TechniqueHumansIntracellular SpaceLapatinibMaytansineMiddle AgedNeoplasms, Cystic, Mucinous, and SerousOvarian NeoplasmsProtein DomainsQuinazolinesReceptor, ErbB-2Retrospective StudiesTissue Array AnalysisTrastuzumabUterine NeoplasmsConceptsUterine serous carcinomaOvarian serous carcinomaHER2 intracellular domainSerous carcinomaECD levelsECD statusTissue microarrayHER2 measurementQuantitative immunofluorescenceHER2 overexpression/amplificationClinico-pathologic characteristicsClinico-pathological featuresHER2-targeted agentsIntracellular domainOverexpression/amplificationHER2 extracellular domainExtracellular domainOSC patientsClinical trialsBreast cancerClinical significancePatientsHER2 assaysP95-HER2CarcinomaPathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial
Shi W, Jiang T, Nuciforo P, Hatzis C, Holmes E, Harbeck N, Sotiriou C, Peña L, Loi S, Rosa DD, Chia S, Wardley A, Ueno T, Rossari J, Eidtmann H, Armour A, Piccart-Gebhart M, Rimm DL, Baselga J, Pusztai L. Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial. Annals Of Oncology 2017, 28: 128-135. PMID: 28177460, PMCID: PMC5834036, DOI: 10.1093/annonc/mdw434.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiopsy, Fine-NeedleBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDNA, NeoplasmExome SequencingFemaleHumansLapatinibMolecular Targeted TherapyMutationProportional Hazards ModelsProtein Kinase InhibitorsQuinazolinesReceptor, ErbB-2RhoA GTP-Binding ProteinTrastuzumabConceptsPathologic complete response
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 timeMeasurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer
Carvajal-Hausdorf DE, Schalper KA, Pusztai L, Psyrri A, Kalogeras KT, Kotoula V, Fountzilas G, Rimm DL. Measurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer. Journal Of The National Cancer Institute 2015, 107: djv136. PMID: 25991002, PMCID: PMC4554192, DOI: 10.1093/jnci/djv136.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantClinical Trials as TopicDisease-Free SurvivalExtracellular SpaceFemaleFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansIntracellular SpaceKaplan-Meier EstimateMiddle AgedPredictive Value of TestsPrognosisReceptor, ErbB-2Sensitivity and SpecificityTissue Array AnalysisTrastuzumabTreatment OutcomeConceptsHuman epidermal growth factor receptor 2ECD expressionICD statusLonger DFSQuantitative immunofluorescenceTrastuzumab therapyPrognostic valueBreast cancerTissue microarrayEpidermal growth factor receptor 2Adjuvant trastuzumab therapyDisease-free survival analysisTrastuzumab-treated patientsGrowth factor receptor 2High positive predictive valueHER2-positive tumorsKaplan-Meier estimatesFactor receptor 2ERBB2 gene amplificationHER2 protein expressionPositive predictive valueExtracellular domainAdjuvant chemotherapyHER2-ICDBetter DFS
2014
EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial
Cheng H, Ballman K, Vassilakopoulou M, Dueck AC, Reinholz MM, Tenner K, Gralow J, Hudis C, Davidson NE, Fountzilas G, McCullough AE, Chen B, Psyrri A, Rimm DL, Perez EA. EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial. British Journal Of Cancer 2014, 111: 1065-1071. PMID: 25117817, PMCID: PMC4453859, DOI: 10.1038/bjc.2014.442.Peer-Reviewed Original ResearchConceptsNorth Central Cancer Treatment GroupMetastatic breast cancer cohortEpidermal growth factor receptorBreast cancer cohortHigh EGFR expressionEGFR expressionConcurrent trastuzumabGrowth factor receptorCancer cohortEGFR antibodyNCCTG N9831 trialsAnti-HER2 therapyCancer Treatment GroupDisease-free survivalFactor receptorN9831 trialsSequential trastuzumabAdditive therapyArm AClinical outcomesTreatment optionsWorse outcomesArm CTissue microarrayTreatment groupsIn Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients
Vassilakopoulou M, Togun T, Dafni U, Cheng H, Bordeaux J, Neumeister VM, Bobos M, Pentheroudakis G, Skarlos DV, Pectasides D, Kotoula V, Fountzilas G, Rimm DL, Psyrri A. In Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients. PLOS ONE 2014, 9: e99131. PMID: 24968015, PMCID: PMC4072595, DOI: 10.1371/journal.pone.0099131.Peer-Reviewed Original ResearchConceptsBreast cancer patientsMetastatic breast cancer patientsFISH HER2Cancer patientsHER2 mRNAPrognostic factorsTrastuzumab-treated metastatic breast cancer patientsMultivariate Cox regression modelECD HER2Log rank pMetastatic breast cancerStrong prognostic factorCox regression modelKaplan-Meier estimatesHER2 mRNA levelsHER2-ICDChemotherapy regimensMetastatic cohortTrastuzumab treatmentBreast cancerTissue microarrayMRNA statusPerformance of markersHER2 receptorPredictive valueIn 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 Analysis