2021
Alpha-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-SMAAutomated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma
Moore MR, Friesner ID, Rizk EM, Fullerton BT, Mondal M, Trager MH, Mendelson K, Chikeka I, Kurc T, Gupta R, Rohr BR, Robinson EJ, Acs B, Chang R, Kluger H, Taback B, Geskin LJ, Horst B, Gardner K, Niedt G, Celebi JT, Gartrell-Corrado RD, Messina J, Ferringer T, Rimm DL, Saltz J, Wang J, Vanguri R, Saenger YM. Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma. Scientific Reports 2021, 11: 2809. PMID: 33531581, PMCID: PMC7854647, DOI: 10.1038/s41598-021-82305-1.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiopsyChemotherapy, AdjuvantClinical Decision-MakingDeep LearningFemaleFollow-Up StudiesHumansImage Processing, Computer-AssistedKaplan-Meier EstimateLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedNeoplasm StagingPatient SelectionPrognosisRetrospective StudiesRisk AssessmentROC CurveSkinSkin NeoplasmsYoung AdultConceptsTumor-infiltrating lymphocytesDisease-specific survivalEarly-stage melanomaOpen-source deep learningCutoff valueMultivariable Cox proportional hazards analysisCox proportional hazards analysisDeep learningLow-risk patientsProportional hazards analysisKaplan-Meier analysisAccurate prognostic biomarkersEosin imagesAccuracy of predictionAdjuvant therapyRisk patientsSpecific survivalPrognostic valueValidation cohortReceiver operating curvesTraining cohortTIL analysisClinical trialsPrimary melanomaPrognostic biomarker
2018
Tumor infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment breast cancers in the SWOG S0800 Phase II neoadjuvant chemotherapy trial
Pelekanou V, Barlow WE, Nahleh Z, Wasserman B, Lo YC, von Wahlde MK, Hayes D, Hortobagyi GN, Gralow J, Tripathy D, Porter P, Szekely B, Hatzis C, Rimm DL, Pusztai L. Tumor infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment breast cancers in the SWOG S0800 Phase II neoadjuvant chemotherapy trial. Molecular Cancer Therapeutics 2018, 17: molcanther.1005.2017. PMID: 29588392, PMCID: PMC6548451, DOI: 10.1158/1535-7163.mct-17-1005.Peer-Reviewed Original ResearchConceptsPD-L1 expressionPathologic complete responseTIL countPosttreatment tissuePD-L1Estrogen receptorImmune checkpoint inhibitor therapyPD-L1 positivity rateTumor-infiltrating lymphocyte countsDoxorubicin/cyclophosphamideCheckpoint inhibitor therapyPD-L1 levelsMol Cancer TherNab-paclitaxelLymphocyte countResidual cancerComplete responseER statusImmune changesInhibitor therapyCox regressionPatient populationControl armClinical trialsPositivity rate
2016
Validation of the IHC4 Breast Cancer Prognostic Algorithm Using Multiple Approaches on the Multinational TEAM Clinical Trial
Bartlett JM, Christiansen J, Gustavson M, Rimm DL, Piper T, van de Velde CJ, Hasenburg A, Kieback DG, Putter H, Markopoulos CJ, Dirix LY, Seynaeve C, Rea DW. Validation of the IHC4 Breast Cancer Prognostic Algorithm Using Multiple Approaches on the Multinational TEAM Clinical Trial. Archives Of Pathology & Laboratory Medicine 2016, 140: 66-74. PMID: 26717057, DOI: 10.5858/arpa.2014-0599-oa.Peer-Reviewed Original ResearchConceptsHazard ratioBreast cancerResidual riskMultivariate Cox proportional hazardsDistant recurrence-free survivalClinical prognostic factorsEarly breast cancerRecurrence-free survivalSignificant prognostic valueCox proportional hazardsHER2/neuIHC4 scoreHormone therapyNodal statusTrial cohortPrognostic factorsPrognostic valueClinical trialsKi-67Proportional hazardsMultivariate analysisTEAM trialBiomarker expressionQuantitative immunofluorescenceResidual risk assessment
2015
Measurement 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 DFSPD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer
Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, Bossuyt V, Pusztai L, Lannin DR, Rimm DL. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer Immunology Research 2015, 3: 326-332. PMID: 25527356, PMCID: PMC4390454, DOI: 10.1158/2326-6066.cir-14-0133.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesPD-L1 expressionPathologic complete responseNeoadjuvant chemotherapyPD-L1Breast cancerDeath 1 ligand 1PD-L1 protein expressionYale-New Haven HospitalHigh PD-L1Antitumor immune activitySubset of patientsTriple-negative patientsBreast cancer patientsTriple-negative statusImmune checkpoint proteinsImmune regulatory moleculesNew Haven HospitalSignificant multivariate modelRabbit monoclonal antibodyTILs correlateComplete responseImmune therapyCancer patientsImmune activity
2014
Multiplexed Quantitative Analysis of CD3, CD8, and CD20 Predicts Response to Neoadjuvant Chemotherapy in Breast Cancer
Brown JR, Wimberly H, Lannin DR, Nixon C, Rimm DL, Bossuyt V. Multiplexed Quantitative Analysis of CD3, CD8, and CD20 Predicts Response to Neoadjuvant Chemotherapy in Breast Cancer. Clinical Cancer Research 2014, 20: 5995-6005. PMID: 25255793, PMCID: PMC4252785, DOI: 10.1158/1078-0432.ccr-14-1622.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntigens, CD20Antineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCD3 ComplexCD8 AntigensChemotherapy, AdjuvantFemaleHumansImmunophenotypingLymphocyte SubsetsLymphocytes, Tumor-InfiltratingMiddle AgedNeoadjuvant TherapyNeoplasm GradingNeoplasm StagingPrognosisReproducibility of ResultsTreatment OutcomeTumor BurdenConceptsTumor-infiltrating lymphocytesPathologic complete responseBreast cancerTonsil specimensPredictive valueAQUA scoreQuantitative immunofluorescenceFlow cytometryFuture larger studiesPathologist estimationNeoadjuvant cohortNeoadjuvant chemotherapyNeoadjuvant therapyLymphocyte infiltratesTIL countComplete responseNodal statusLymphocyte percentageLymphocyte subpopulationsStromal expressionNuclear gradeUnivariate analysisKi-67CD8Clinical utilityQuantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab
Cheng H, Bai Y, Sikov W, Sinclair N, Bossuyt V, Abu-Khalaf MM, Harris LN, Rimm DL. Quantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab. BMC Cancer 2014, 14: 326. PMID: 24885187, PMCID: PMC4037428, DOI: 10.1186/1471-2407-14-326.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAlbuminsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCarboplatinChemotherapy, AdjuvantConnecticutFemaleFluorescent Antibody TechniqueHumansNeoadjuvant TherapyPaclitaxelPhosphorylationProteomicsReceptor, ErbB-2Rhode IslandTime FactorsTrastuzumabTreatment OutcomeConceptsLikelihood of responsePhospho-HER2Nab-paclitaxelPathologic responseHER2 levelsAdvanced HER2-positive breast cancerHER2-positive breast cancerCarboplatin combination therapyPre-surgical settingPreoperative clinical trialSingle-agent trastuzumabPathologic complete responseInitiation of treatmentWeeks of treatmentBreast cancer patientsTumor core biopsiesCore biopsy samplesMonoclonal antibody trastuzumabEvaluable patientsNeoadjuvant regimenNeoadjuvant chemotherapyNeoadjuvant therapyNeoadjuvant treatmentComplete responsePreoperative setting
2013
Prediction 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
Association between the nuclear to cytoplasmic ratio of p27 and the efficacy of adjuvant polychemotherapy in early breast cancer
Andre F, Conforti R, Moeder CB, Mauguen A, Arnedos M, Berrada N, Delaloge S, Tomasic G, Spielmann M, Esteva FJ, Rimm DL, Michiels S. Association between the nuclear to cytoplasmic ratio of p27 and the efficacy of adjuvant polychemotherapy in early breast cancer. Annals Of Oncology 2012, 23: 2059-2064. PMID: 22241898, DOI: 10.1093/annonc/mdr569.Peer-Reviewed Original ResearchConceptsAnthracycline-based chemotherapyEarly breast cancerNuclear/cytoplasmic (N/C) ratioCytoplasmic ratioAdjuvant chemotherapyHazard ratioBreast cancerP27 expressionNuclear expressionAdjusted hazard ratioNuclear p27 expressionAdjuvant polychemotherapyUntreated armPrognostic parametersTissue microarrayChemotherapyPatientsPredictive valueImmunofluorescence assaysQuantitative immunofluorescence assaysEfficacyP27CancerExpressionPolychemotherapy
2010
Multiplexed Assessment of the Southwest Oncology Group-Directed Intergroup Breast Cancer Trial S9313 by AQUA Shows that Both High and Low Levels of HER2 Are Associated with Poor Outcome
Harigopal M, Barlow WE, Tedeschi G, Porter PL, Yeh IT, Haskell C, Livingston R, Hortobagyi GN, Sledge G, Shapiro C, Ingle JN, Rimm DL, Hayes DF. Multiplexed Assessment of the Southwest Oncology Group-Directed Intergroup Breast Cancer Trial S9313 by AQUA Shows that Both High and Low Levels of HER2 Are Associated with Poor Outcome. American Journal Of Pathology 2010, 176: 1639-1647. PMID: 20150438, PMCID: PMC2843456, DOI: 10.2353/ajpath.2010.090711.Peer-Reviewed Original ResearchConceptsDisease-free survivalEstrogen receptorContinuous variablesSouthwest Oncology GroupAQUA methodAC chemotherapyMenopausal statusNegative patientsOncology GroupNode statusSequential doxorubicinPoor outcomeTumor sizeProgesterone receptorPrognostic informationWorse outcomesTissue biomarkersTissue microarrayBiphasic effectP53 expressionPatientsHER2Low expressersDiagnostic approachMultiplexed assessment