2023
Correlation of HER2 Protein Level With mRNA Level Quantified by RNAscope in Breast Cancer
Li X, Lee J, Gao Y, Zhang J, Bates K, Rimm D, Zhang H, Smith G, Lawson D, Meisel J, Chang J, Huo L. Correlation of HER2 Protein Level With mRNA Level Quantified by RNAscope in Breast Cancer. Modern Pathology 2023, 37: 100408. PMID: 38135153, DOI: 10.1016/j.modpat.2023.100408.Peer-Reviewed Original ResearchHER2 protein levelsHER2-low breast cancerT-DXdBreast cancerRNA levelsProtein levelsHER2 expressionEarly-stage breast cancerIHC H-scoresTrastuzumab deruxtecanTissue microarray coresClinical trialsMetastatic biopsiesImmunohistochemical assaysH-scoreDrug AdministrationResponse rateUS FoodPatientsIHC assaysCancerRNAscopeRegression analysisCell linesImmunofluorescence scores
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 rangeP2.12-01 Intratumoral Conventional Type 1 Dendritic Cells (cDC1s) Predict Response to Immunotherapy in Human Non-small Cell Lung Cancer cancer (NSCLC)
Porciuncula A, Henick B, Gianino N, Zugazagoitia J, Vathiotis I, Gavrielatou N, Zacharek S, Rimm D, Schalper K. P2.12-01 Intratumoral Conventional Type 1 Dendritic Cells (cDC1s) Predict Response to Immunotherapy in Human Non-small Cell Lung Cancer cancer (NSCLC). Journal Of Thoracic Oncology 2022, 17: s150. DOI: 10.1016/j.jtho.2022.07.249.Peer-Reviewed Original ResearchPrediction of pathologic complete response to neoadjuvant chemotherapy in breast cancer (SWOG S0800) using image analysis-based tumor infiltrating lymphocyte measurements.
Blenman K, Fanucci K, Bai Y, Pelekanou V, Nahleh Z, Shafi S, Burela S, Barlow W, Sharma P, Thompson A, Godwin A, Rimm D, Hortobagyi G, Pusztai L. Prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancer (SWOG S0800) using image analysis-based tumor infiltrating lymphocyte measurements. Journal Of Clinical Oncology 2022, 40: 594-594. DOI: 10.1200/jco.2022.40.16_suppl.594.Peer-Reviewed Original ResearchPathologic complete responseBreast cancerNeoadjuvant chemotherapyComplete responseTIL scoreResidual diseaseResponse predictive markersBetter EFSBevacizumab benefitLymphocyte measurementsTIL assessmentFree survivalPredictive markerTIL quantificationInternational guidelinesPretreatment samplesLogistic regressionCancerOutcome discriminationChemotherapyScoresContinuous scoresTumorsClinical adoptionStrong positive correlation
2021
The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group
El Bairi K, Haynes HR, Blackley E, Fineberg S, Shear J, Turner S, de Freitas JR, Sur D, Amendola LC, Gharib M, Kallala A, Arun I, Azmoudeh-Ardalan F, Fujimoto L, Sua LF, Liu SW, Lien HC, Kirtani P, Balancin M, El Attar H, Guleria P, Yang W, Shash E, Chen IC, Bautista V, Do Prado Moura JF, Rapoport BL, Castaneda C, Spengler E, Acosta-Haab G, Frahm I, Sanchez J, Castillo M, Bouchmaa N, Md Zin RR, Shui R, Onyuma T, Yang W, Husain Z, Willard-Gallo K, Coosemans A, Perez EA, Provenzano E, Ericsson PG, Richardet E, Mehrotra R, Sarancone S, Ehinger A, Rimm DL, Bartlett JMS, Viale G, Denkert C, Hida AI, Sotiriou C, Loibl S, Hewitt SM, Badve S, Symmans WF, Kim RS, Pruneri G, Goel S, Francis PA, Inurrigarro G, Yamaguchi R, Garcia-Rivello H, Horlings H, Afqir S, Salgado R, Adams S, Kok M, Dieci MV, Michiels S, Demaria S, Loi S. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group. Npj Breast Cancer 2021, 7: 150. PMID: 34853355, PMCID: PMC8636568, DOI: 10.1038/s41523-021-00346-1.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesImmune checkpoint inhibitorsInternational Immuno-Oncology Biomarker Working GroupBiomarker Working GroupBreast cancerTriple-negative breast cancerSubgroup of womenDeath-1Middle-income countriesPD-L1TIL analysisCytotoxic treatmentCancer settingPrognostic biomarkerClinical utilityClinical validityPatient advocatesWorking GroupClinical utilizationModern oncologyPatientsLymphocytesCancerFuture approachesImmunotherapyDeep 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 standardImmunohistochemistryHematoxylin
2020
The Society for Immunotherapy of Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation
Taube JM, Akturk G, Angelo M, Engle EL, Gnjatic S, Greenbaum S, Greenwald NF, Hedvat CV, Hollmann TJ, Juco J, Parra ER, Rebelatto MC, Rimm DL, Rodriguez-Canales J, Schalper KA, Stack EC, Ferreira CS, Korski K, Lako A, Rodig SJ, Schenck E, Steele KE, Surace MJ, Tetzlaff MT, von Loga K, Wistuba II, Bifulco CB, . The Society for Immunotherapy of Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation. Journal For ImmunoTherapy Of Cancer 2020, 8: e000155. PMID: 32414858, PMCID: PMC7239569, DOI: 10.1136/jitc-2019-000155.Peer-Reviewed Original ResearchConceptsMultiplex immunohistochemistryImmune cell subsetsImmunotherapy of cancerRoutine clinical practiceMultiplex immunofluorescence analysisDigital spatial profilingMIF assayTask ForceTreatment of cancerCell subsetsPractice guidelinesBest practice guidelinesAcademic centersClinical practiceImmune systemTumor microenvironmentImmunohistochemistryTumor cellsBiomarker studiesCancer statementsChromogenic immunohistochemistryImmunotherapyImmunofluorescence analysisConsecutive stainingCancerApplication of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
Hudeček J, Voorwerk L, van Seijen M, Nederlof I, de Maaker M, van den Berg J, van de Vijver KK, Sikorska K, Adams S, Demaria S, Viale G, Nielsen TO, Badve SS, Michiels S, Symmans WF, Sotiriou C, Rimm DL, Hewitt SM, Denkert C, Loibl S, Loi S, Bartlett JMS, Pruneri G, Dillon DA, Cheang MCU, Tutt A, Hall JA, Kos Z, Salgado R, Kok M, Horlings HM. Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials. Npj Breast Cancer 2020, 6: 15. PMID: 32436923, PMCID: PMC7217941, DOI: 10.1038/s41523-020-0155-1.Peer-Reviewed Original ResearchStromal tumor-infiltrating lymphocytesTriple-negative breast cancerMetastatic triple-negative breast cancerTumor-infiltrating lymphocytesClinical trialsBiomarker-driven clinical trialsPotential predictive biomarkersPotential risk factorsImmunotherapy trialsImmunotherapy responsePredictive biomarkersRisk factorsBreast cancerStratification factorsSpecific trialsIntegral biomarkerTrialsLymphocytesBiomarkersReliable assessmentReviewCancerPitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer
Kos Z, Roblin E, Kim RS, Michiels S, Gallas BD, Chen W, van de Vijver KK, Goel S, Adams S, Demaria S, Viale G, Nielsen TO, Badve SS, Symmans WF, Sotiriou C, Rimm DL, Hewitt S, Denkert C, Loibl S, Luen SJ, Bartlett JMS, Savas P, Pruneri G, Dillon DA, Cheang MCU, Tutt A, Hall JA, Kok M, Horlings HM, Madabhushi A, van der Laak J, Ciompi F, Laenkholm AV, Bellolio E, Gruosso T, Fox SB, Araya JC, Floris G, Hudeček J, Voorwerk L, Beck AH, Kerner J, Larsimont D, Declercq S, Van den Eynden G, Pusztai L, Ehinger A, Yang W, AbdulJabbar K, Yuan Y, Singh R, Hiley C, Bakir MA, Lazar AJ, Naber S, Wienert S, Castillo M, Curigliano G, Dieci MV, André F, Swanton C, Reis-Filho J, Sparano J, Balslev E, Chen IC, Stovgaard EIS, Pogue-Geile K, Blenman KRM, Penault-Llorca F, Schnitt S, Lakhani SR, Vincent-Salomon A, Rojo F, Braybrooke JP, Hanna MG, Soler-Monsó MT, Bethmann D, Castaneda CA, Willard-Gallo K, Sharma A, Lien HC, Fineberg S, Thagaard J, Comerma L, Gonzalez-Ericsson P, Brogi E, Loi S, Saltz J, Klaushen F, Cooper L, Amgad M, Moore DA, Salgado R. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. Npj Breast Cancer 2020, 6: 17. PMID: 32411819, PMCID: PMC7217863, DOI: 10.1038/s41523-020-0156-0.Peer-Reviewed Original ResearchStromal tumor-infiltrating lymphocytesEarly TNBCBreast cancerHER2-positive breast cancerTumor-infiltrating lymphocytesLymphocyte distributionStromal tumorsInflammatory cellsPredictive biomarkersTreatment selectionPrognostic toolClinical practiceOutcome estimatesLymphocytesReproducible assessmentTNBCTumorsCancerScoring guidelinesMultiple areasTumor boundariesRisk estimationImpact of discrepanciesRing studiesAssessment
2019
MA25.02 Arrangement and Architecture of Tumor-Infiltrating Lymphocyte on H&E Slides Predict OS in Nivolumab Treated Non-Small Cell Lung Cancer
Wang X, Barrera C, Bera K, Lu C, Feldman M, Schalper K, Rimm D, Velcheti V, Madabhushi A. MA25.02 Arrangement and Architecture of Tumor-Infiltrating Lymphocyte on H&E Slides Predict OS in Nivolumab Treated Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: s350-s351. DOI: 10.1016/j.jtho.2019.08.710.Peer-Reviewed Original ResearchImmunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes
Doroshow DB, Sanmamed MF, Hastings K, Politi K, Rimm DL, Chen L, Melero I, Schalper KA, Herbst RS. Immunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes. Clinical Cancer Research 2019, 25: 4592-4602. PMID: 30824587, PMCID: PMC6679805, DOI: 10.1158/1078-0432.ccr-18-1538.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNon-small cell lung cancerImmune checkpoint inhibitorsCell lung cancerPD-L1Lung cancerNonsquamous non-small cell lung cancerOngoing translational workPD-1 axisFirst-line therapyPD-L1 expressionProportion of patientsTumor mutational burdenAdvanced diseaseOverall survivalTumor inflammationMutational burdenPatientsNovel markerChemotherapyTherapyIndicative biomarkersCancerTranslational workBiomarkersSurvivalReanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer
Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, Roden AC, Hirsch FR, Wistuba II, Pusztai L. Reanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer. Breast Cancer Research 2019, 21: 72. PMID: 31196152, PMCID: PMC6567382, DOI: 10.1186/s13058-019-1156-6.Peer-Reviewed Original ResearchConceptsPD-L1 expressionImmune cell PD-L1 expressionLung cancerImmune cellsTriple-negative breast cancerEasy scoring methodCompanion diagnostic testsPD-L1Immune therapyBreast cancerImmunohistochemical testsBetter outcomesLarger studyTumor cellsDiagnostic testsCancerExpression findingsCellsExpressionPoor agreementScoring methodTherapyTrialsPhenotyping tumor infiltrating lymphocytes (PhenoTIL) on H&E tissue images: predicting recurrence in lung cancer
Barrera C, Corredor G, Wang X, Schalper K, Rimm D, Velcheti V, Madabhushi A, Castro E. Phenotyping tumor infiltrating lymphocytes (PhenoTIL) on H&E tissue images: predicting recurrence in lung cancer. Progress In Biomedical Optics And Imaging 2019, 10956: 1095607-1095607-8. DOI: 10.1117/12.2513048.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesTIL densityLung cancerEarly stage non-small cell lung cancer patientsNon-small cell lung cancer patientsCell lung cancer patientsEarly-stage lung cancerKaplan-Meier analysisLung cancer patientsStage lung cancerLikelihood of recurrenceBetter prognosisLate recurrenceCancer patientsDifferent cancer typesDisease outcomeRecurrenceDifferent subtypesCancer typesLymphocytesCancerPatientsPrognosisIndependent validationCorrection: RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM. Correction: RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clinical Cancer Research 2019, 25: 1437-1437. PMID: 30770496, DOI: 10.1158/1078-0432.ccr-18-4264.Peer-Reviewed Original Research
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 scoreCancerPD-1/PD-L1 interaction and CD25/FOXP3+ t cells to predict survival benefit from adjuvant chemotherapy in early stage non–small-cell lung cancer (ES-NSCLC).
Bordeaux J, Dakappagari N, Pennell N, Stevenson J, Khunger M, Vaupel C, Schalper K, Rimm D, Velcheti V. PD-1/PD-L1 interaction and CD25/FOXP3+ t cells to predict survival benefit from adjuvant chemotherapy in early stage non–small-cell lung cancer (ES-NSCLC). Journal Of Clinical Oncology 2018, 36: 12059-12059. DOI: 10.1200/jco.2018.36.15_suppl.12059.Peer-Reviewed Original ResearchPrognostic implications of residual disease (RD) tumor-infiltrating lymphocytes (TIL) in triple negative breast cancer (TNBC) after neo-adjuvant chemotherapy (NAC).
Luen S, Salgado R, Dieci M, Vingiani A, Curigliano G, Hubbard R, Castaneda Altamirano C, Sanchez J, D'Alfonso T, Cheng E, Castillo Garcia M, Adams S, Ahmed F, Rimm D, Demaria S, Symmans W, Michiels S, Loi S. Prognostic implications of residual disease (RD) tumor-infiltrating lymphocytes (TIL) in triple negative breast cancer (TNBC) after neo-adjuvant chemotherapy (NAC). Journal Of Clinical Oncology 2018, 36: 571-571. DOI: 10.1200/jco.2018.36.15_suppl.571.Peer-Reviewed Original ResearchExpression and clinical significance of antigen presentation components beta-2 microglobulin, HLA class I heavy chains, and HLA class II in non-small cell lung cancer (NSCLC).
Datar I, Villarroel-Espindola F, Henick B, Syrigos K, Toki M, Rimm D, Ferrone S, Herbst R, Schalper K. Expression and clinical significance of antigen presentation components beta-2 microglobulin, HLA class I heavy chains, and HLA class II in non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2018, 36: 12015-12015. DOI: 10.1200/jco.2018.36.15_suppl.12015.Peer-Reviewed Original ResearchAn assessment of neuronal calcium sensor-1 and response to neoadjuvant chemotherapy in breast cancer patients
Moore LM, Wilkinson R, Altan M, Toki M, Carvajal-Hausdorf DE, McGuire J, Ehrlich BE, Rimm DL. An assessment of neuronal calcium sensor-1 and response to neoadjuvant chemotherapy in breast cancer patients. Npj Breast Cancer 2018, 4: 6. PMID: 29560416, PMCID: PMC5847580, DOI: 10.1038/s41523-018-0057-7.Peer-Reviewed Original ResearchTaxane-based neoadjuvant chemotherapyPathological complete responseNeuronal calcium sensor-1Neoadjuvant chemotherapyNCS-1 expressionBreast cancer patientsPoor clinical outcomeEfficacy of paclitaxelBreast cancer biopsiesComplete responseClinical outcomesCancer patientsPredictive biomarkersBreast cancerCancer biopsiesChemotherapyElevated expressionPaclitaxelPrevious studiesResponseBiopsyPatientsExpressionTaxanesCancer
2017
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer. Cancer Discovery 2017, 7: cd-17-0593. PMID: 29025772, PMCID: PMC5718941, DOI: 10.1158/2159-8290.cd-17-0593.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPatient-derived xenograftsHLA class ILung cancerClass ICell surface HLA class ILung cancer mouse modelPD-1 blockadeStandard treatment algorithmCancer mouse modelLung cancer samplesDefective antigen processingCheckpoint inhibitorsPD-1Treatment algorithmMouse modelAntagonistic antibodiesDiverse malignanciesAntigen processingCancer samplesB2MHomozygous lossTumorsCancerRecurrent mutations