2024
The analytical and clinical validity of AI algorithms to score TILs in TNBC: can we use different machine learning models interchangeably?
Vidal J, Tsiknakis N, Staaf J, Bosch A, Ehinger A, Nimeus E, Salgado R, Bai Y, Rimm D, Hartman J, Acs B. The analytical and clinical validity of AI algorithms to score TILs in TNBC: can we use different machine learning models interchangeably? EClinicalMedicine 2024, 78: 102928. DOI: 10.1016/j.eclinm.2024.102928.Peer-Reviewed Original ResearchTriple-negative breast cancerTumor-infiltrating lymphocytesBreast Cancer Research FoundationPrognostic validityMetastatic triple-negative breast cancerDisease-free survival endpointsHazard ratioHost anti-tumor immunityScored tumor infiltrating lymphocytesTumor-infiltrating lymphocyte scoresTriple-negative breast cancer patientsYears median follow-upTumour-infiltrating lymphocyte assessmentAnti-tumor immunityMedian follow-upIndependent prospective cohortTNBC tumorsPrognostic potentialProspective cohortBreast cancerPrognostic performanceAnalytic cohortFollow-upSchool of MedicineSwedish Society for Medical ResearchQuantitative Measurement of HER2 Expression in Non–Small Cell Lung Cancer With a High-Sensitivity Assay
Liu M, Vathiotis I, Robbins C, Chan N, Moutafi M, Burela S, Xirou V, Schalper K, Herbst R, Syrigos K, Rimm D. Quantitative Measurement of HER2 Expression in Non–Small Cell Lung Cancer With a High-Sensitivity Assay. Modern Pathology 2024, 37: 100556. PMID: 38964502, PMCID: PMC11416319, DOI: 10.1016/j.modpat.2024.100556.Peer-Reviewed Original ResearchNon-small cell lung cancerCases of non-small cell lung cancerNon-small cell lung cancer casesT-DXdCell lung cancerHER2 expressionBreast cancerRare case of non-small cell lung cancerQuantitative immunofluorescenceAntibody-drug conjugate trastuzumab deruxtecanLung cancerHER2 antibody-drug conjugatesNon-small cell lung cancer patientsDetecting HER2 expressionHER2-targeted therapyMetastatic breast cancerHER2 protein expressionBreast cancer casesHER2 protein levelsAntibody-drug conjugatesProportion of casesTrastuzumab deruxtecanNSCLC casesFrequency of casesImmunohistochemistry scoreSACI-IO HR+: A randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in patients with metastatic hormone receptor-positive/HER2-negative breast cancer.
Garrido-Castro A, Kim S, Desrosiers J, Nanda R, Carey L, Clark A, Sacks R, O'Connor T, Sinclair N, Lo K, Thomas A, Wrabel E, O'Meara T, Lin N, Burstein H, He M, Rimm D, Mittendorf E, Tayob N, Tolaney S. SACI-IO HR+: A randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in patients with metastatic hormone receptor-positive/HER2-negative breast cancer. Journal Of Clinical Oncology 2024, 42: lba1004-lba1004. DOI: 10.1200/jco.2024.42.17_suppl.lba1004.Peer-Reviewed Original ResearchProgression-free survivalMetastatic breast cancerHR+/HER2- metastatic breast cancerPD-L1 expressionSacituzumab govitecanAntibody drug conjugatesOverall survivalArm BPD-L1Arm ASN-38Study therapyBreast cancerHormone receptor-positive/HER2-negative breast cancerOpen-label phase 2 studyFollow-upDeplete regulatory T cellsFrequent treatment-related toxicitiesHormone receptor-positive/HER2-negativeImproving progression-free survivalTopoisomerase I inhibitor payloadMedian progression-free survivalRandomized phase II trialUpregulated MHC class IT cell effector function
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 scoresImage analysis-based tumor infiltrating lymphocytes measurement predicts breast cancer pathologic complete response in SWOG S0800 neoadjuvant chemotherapy trial
Fanucci K, Bai Y, Pelekanou V, Nahleh Z, Shafi S, Burela S, Barlow W, Sharma P, Thompson A, Godwin A, Rimm D, Hortobagyi G, Liu Y, Wang L, Wei W, Pusztai L, Blenman K. Image analysis-based tumor infiltrating lymphocytes measurement predicts breast cancer pathologic complete response in SWOG S0800 neoadjuvant chemotherapy trial. Npj Breast Cancer 2023, 9: 38. PMID: 37179362, PMCID: PMC10182981, DOI: 10.1038/s41523-023-00535-0.Peer-Reviewed Original ResearchPathologic complete responseBreast cancerComplete responseTIL scoreBreast Cancer Pathologic Complete ResponseTumor-infiltrating lymphocyte scoresEvent-free survivalNeoadjuvant chemotherapy trialsLymphocyte measurementsLymphocyte scoreNeoadjuvant chemotherapyChemotherapy trialsMean pretreatmentResidual diseaseTIL quantificationPredictive valuePretreatment samplesResponse discriminationScoresStrong positive correlationPositive correlationAssessment of the Impact of Alternative Fixatives on HER2 Detection in Breast Cancer and Gastric Cancer Tumor Specimens
Feng W, Inoue R, Kuwata T, Niikura N, Fujii S, Kumaki N, Honda K, Xu L, Goetz A, Gaule P, Cogswell J, Rimm D, McGee R. Assessment of the Impact of Alternative Fixatives on HER2 Detection in Breast Cancer and Gastric Cancer Tumor Specimens. Applied Immunohistochemistry & Molecular Morphology 2023, 31: 339-345. PMID: 37093713, PMCID: PMC10155692, DOI: 10.1097/pai.0000000000001126.Peer-Reviewed Original ResearchConceptsNeutral buffered formalinNegative percentage agreementPositive percentage agreementOverall percentage agreementBreast cancerPercentage agreementHER2 statusHuman epidermal growth factor receptor 2 (HER2) statusEpidermal growth factor receptor 2 statusTumor samplesCell linesGastric cancer tumorsGastric cancer cell linesTumor tissue samplesClinical trial sitesCancer cell linesHER2 testingTumor specimensReal-world settingTumor tissueCancer tumorsBuffered formalinSitu hybridization assaysType of fixativeCentral laboratoryMulti-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 rangeClinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC.
Foldi J, Kahn A, Silber A, Qing T, Reisenbichler E, Fischbach N, Persico J, Adelson K, Katoch A, Chagpar A, Park T, Blanchard A, Blenman K, Rimm D, Pusztai L. Clinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC. Journal Of Clinical Oncology 2022, 40: 516-516. DOI: 10.1200/jco.2022.40.16_suppl.516.Peer-Reviewed Original ResearchImmune-related adverse eventsTriple-negative breast cancerMultivariate logistic regression analysisPD-L1 statusLogistic regression analysisAA raceOverall survivalPathologic responseClinical trialsBreast cancerEarly-stage triple-negative breast cancerIncidence of irAEsPhase I/II trialPathologic complete response rateSignificant associationPhase I/II clinical trialsBaseline body mass indexSafety of immunotherapyWeekly nab-paclitaxelCharlson Comorbidity IndexComplete response ratePrimary efficacy endpointPD-L1 expressionBody mass indexBreast cancer recurrencePrediction 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 correlationPredictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer.
Blenman KRM, Marczyk M, Karn T, Qing T, Li X, Gunasekharan V, Yaghoobi V, Bai Y, Ibrahim EY, Park T, Silber A, Wolf DM, Reisenbichler E, Denkert C, Sinn BV, Rozenblit M, Foldi J, Rimm DL, Loibl S, Pusztai L. Predictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer. Clinical Cancer Research 2022, 28: 2587-2597. PMID: 35377948, PMCID: PMC9464605, DOI: 10.1158/1078-0432.ccr-21-3215.Peer-Reviewed Original ResearchConceptsBasal-like triple-negative breast cancerPathologic complete responseResidual diseaseNeoadjuvant durvalumabDNA damage repairSomatic mutationsBreast cancerWnt/β-cateninHigh expressionTriple-negative breast cancerBasal-Like TripleDoxorubicin/cyclophosphamideDNA repairTumor mutation burdenRNA sequencingEpithelial-mesenchymal transitionFive-gene signatureB-cell markersCancer driversEnrichment analysisNegative breast cancerDamage repairGene expressionJAK-STATCell cycleExamination 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 ResearchConceptsBreast 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 expressionBiopsyIHCConcordanceImpact of a randomized weight loss trial on breast tissue markers in breast cancer survivors
Dieli-Conwright CM, Harrigan M, Cartmel B, Chagpar A, Bai Y, Li FY, Rimm DL, Pusztai L, Lu L, Sanft T, Irwin ML. Impact of a randomized weight loss trial on breast tissue markers in breast cancer survivors. Npj Breast Cancer 2022, 8: 29. PMID: 35256599, PMCID: PMC8901848, DOI: 10.1038/s41523-022-00396-z.Peer-Reviewed Original ResearchBreast cancer survivorsWeight loss interventionBreast tissue biopsiesUsual careLoss interventionCancer survivorsWeight lossBreast cancerTissue markersTissue biopsiesLifestyle behavioural interventionUsual care groupSerum insulin levelsWeight loss trialWeight loss groupBreast cancer treatmentBreast tissue markersInsulin receptor levelsInflammatory markersAdiponectin levelsSerum leptinCare groupInsulin levelsSerum biomarkersBlood drawAuthor Correction: Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
Foldi J, Silber A, Reisenbichler E, Singh K, Fischbach N, Persico J, Adelson K, Katoch A, Horowitz N, Lannin D, Chagpar A, Park T, Marczyk M, Frederick C, Burrello T, Ibrahim E, Qing T, Bai Y, Blenman K, Rimm DL, Pusztai L. Author Correction: Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer. Npj Breast Cancer 2022, 8: 17. PMID: 35115541, PMCID: PMC8814070, DOI: 10.1038/s41523-022-00392-3.Peer-Reviewed Original ResearchCECR2 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 tumorsMetastasisThe Effect of Black Cohosh on Ki67 expression and Tumor Volume: A Pilot Study of Ductal Carcinoma in Situ Patients
Trant A, Chagpar A, Wei W, Neumeister V, Rimm D, Stavris K, Lurie B, Frederick C, Andrejeva L, Raghu M, Killelea B, Horowitz N, Lannin D, Knill-Selby E, Sturrock T, Hofstatter E. The Effect of Black Cohosh on Ki67 expression and Tumor Volume: A Pilot Study of Ductal Carcinoma in Situ Patients. Integrative Cancer Therapies 2022, 21: 15347354221137290. PMID: 36444764, PMCID: PMC9716631, DOI: 10.1177/15347354221137290.Peer-Reviewed Original ResearchConceptsTumor volumeBlack cohoshSitu patientsDuctal carcinomaAnti-inflammatory effectsTumor cellular proliferationBreast cancer treatmentCellular proliferationWilcoxon signed-rank testDCIS patientsAdverse eventsEligible subjectsWindow trialsCore biopsyInvasive diseaseKi67 expressionSigned-rank testBreast cancerGrade 3Hormone changesPatientsQuantitative immunofluorescenceBC extractSignificant toxicityCancer treatment
2021
Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case–control study
Yaghoobi V, Moutafi M, Aung TN, Pelekanou V, Yaghoubi S, Blenman K, Ibrahim E, Vathiotis IA, Shafi S, Sharma A, O’Meara T, Fernandez AI, Pusztai L, Rimm DL. Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case–control study. Breast Cancer Research 2021, 23: 113. PMID: 34906209, PMCID: PMC8670126, DOI: 10.1186/s13058-021-01493-w.Peer-Reviewed Original ResearchConceptsNegative breast cancerT cellsTumor microenvironmentAA patientsImmune cellsAA tumorsBreast cancerPurposeTriple-negative breast cancerAfrican AmericansTriple-negative breast cancerCase-control studySignificant differencesActivated T cellsImmunologic biomarkersPD-L1Lymphocytic infiltrationLymphoid infiltrationImmune microenvironmentControl cohortTNBC tumorsMyeloid markersQuantitative immunofluorescenceMean expression levelPatientsTNBCThe 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 approachesImmunotherapyInterplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study
Zerdes I, Simonetti M, Matikas A, Harbers L, Acs B, Boyaci C, Zhang N, Salgkamis D, Agartz S, Moreno-Ruiz P, Bai Y, Rimm DL, Hartman J, Mezheyeuski A, Bergh J, Crosetto N, Foukakis T. Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study. Npj Breast Cancer 2021, 7: 144. PMID: 34799582, PMCID: PMC8604966, DOI: 10.1038/s41523-021-00352-3.Peer-Reviewed Original ResearchMultiplexed fluorescent immunohistochemistryPhase II trialII trialEarly breast cancer patientsSomatic copy number alterationsCopy number alterationsEarly breast cancerBreast cancer patientsAbundant immune cellsImmune cell compositionParaffin-embedded tissue samplesNumber alterationsImmune profilePD-1PD-L1Immune profilingLymphocytic infiltrationCancer patientsImmune cellsBreast cancerT cellsLarge cohortFluorescent immunohistochemistryTissue samplesPathological samplesInterobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group
Van Bockstal MR, Cooks M, Nederlof I, Brinkhuis M, Dutman A, Koopmans M, Kooreman L, van der Vegt B, Verhoog L, Vreuls C, Westenend P, Kok M, van Diest PJ, Nauwelaers I, Laudus N, Denkert C, Rimm D, Siziopikou KP, Ely S, Zardavas D, Roberts M, Floris G, Hartman J, Acs B, Peeters D, Bartlett JMS, Dequeker E, Salgado R, Giudici F, Michiels S, Horlings H, van Deurzen CHM. Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group. Cancers 2021, 13: 4910. PMID: 34638394, PMCID: PMC8507620, DOI: 10.3390/cancers13194910.Peer-Reviewed Original ResearchTumor-Infiltrating LymphocytesPD-L1 statusTNBC metastasisPrimary TNBCInterobserver agreementInternational Immuno-Oncology Biomarker Working GroupTriple-negative breast cancerBiomarker Working GroupBreast cancer benefitIndividual patient levelChance of treatmentCancer benefitDistant metastasisMetastatic TNBCImmune cellsSame pathologistPatient levelBreast cancerAnatomic localizationConsensus diagnosisMetastatic specimensMetastasisInter-pathologist agreementTNBCModerate agreement