2022
Predictive 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 cycle
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 levelPatientsTNBCCharacterization of the tumor immune microenvironment of triple-negative breast cancer (TNBC) patients who self-identify as African American (AA) or non-African American (NonAA).
Blenman K, Marczyk M, Qing T, O'Meara T, Yaghoobi V, Pelekanou V, Bai Y, Reisenbichler E, Li X, Gunasekharan V, Ibrahim E, Rimm D, Pusztai L, Cole K. Characterization of the tumor immune microenvironment of triple-negative breast cancer (TNBC) patients who self-identify as African American (AA) or non-African American (NonAA). Journal Of Clinical Oncology 2021, 39: 564-564. DOI: 10.1200/jco.2021.39.15_suppl.564.Peer-Reviewed Original ResearchTriple-negative breast cancerTumor immune microenvironmentAA patientsImmune microenvironmentWhole-exome sequencingAfrican AmericansTriple-negative breast cancer patientsYale Cancer CenterImmune checkpoint inhibitorsPD-L1 positivityPD-L1 expressionYear of diagnosisBreast cancer patientsCytokines/chemokinesImmune cell compositionTumor mutational burdenGermline whole-exome sequencingAge of diagnosisNegative breast cancerCorresponding clinical dataAllograft rejection pathwayNon-African AmericansSomatic mutationsFatty acid metabolismCheckpoint inhibitors
2020
Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers
Rozenblit M, Huang R, Danziger N, Hegde P, Alexander B, Ramkissoon S, Blenman K, Ross JS, Rimm DL, Pusztai L. Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers. Journal For ImmunoTherapy Of Cancer 2020, 8: e001558. PMID: 33239417, PMCID: PMC7689582, DOI: 10.1136/jitc-2020-001558.Peer-Reviewed Original ResearchConceptsPD-L1 positivity ratePD-L1 positivityPD-L1 expressionDifferent metastatic sitesPrimary tumorMetastatic sitesPositivity rateImmune cellsMetastatic lesionsTumor cellsPD-L1 protein expressionTriple-negative breast cancerMore primary tumorsTriple negative breast cancer tumorsPrimary breast lesionsPrimary outcome measureSoft tissueNegative breast cancerLow positivity rateBreast cancer tumorsBone metastasesFoundation MedicineLymph nodesPD-L1Spearman correlation coefficientImmunological Differences Between Immune-Rich Estrogen Receptor–Positive and Immune-Rich Triple-Negative Breast Cancers
O’Meara T, Marczyk M, Qing T, Yaghoobi V, Blenman K, Cole K, Pelekanou V, Rimm DL, Pusztai L. Immunological Differences Between Immune-Rich Estrogen Receptor–Positive and Immune-Rich Triple-Negative Breast Cancers. JCO Precision Oncology 2020, 4: po.19.00350. PMID: 32923897, PMCID: PMC7446500, DOI: 10.1200/po.19.00350.Peer-Reviewed Original ResearchER-positive breast cancerTriple-negative BCM2-like macrophagesTumor-infiltrating lymphocytesBreast cancerImmune-related genesEstrogen receptor-positive breast cancerImmuno-oncology therapeutic targetsRegulatory T cell markersReceptor-positive breast cancerTriple-negative breast cancerImmune activation markersT-cell markersImmune cell markersM1-like macrophagesDifferent immunotherapy strategiesBreast Cancer International ConsortiumNegative breast cancerImmuno-oncology trialsTGF-β pathwayAntitumor immunityCancer Genome AtlasImmunotherapy strategiesActivation markersImmune microenvironmentProspective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer
Reisenbichler ES, Han G, Bellizzi A, Bossuyt V, Brock J, Cole K, Fadare O, Hameed O, Hanley K, Harrison BT, Kuba MG, Ly A, Miller D, Podoll M, Roden AC, Singh K, Sanders MA, Wei S, Wen H, Pelekanou V, Yaghoobi V, Ahmed F, Pusztai L, Rimm DL. Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer. Modern Pathology 2020, 33: 1746-1752. PMID: 32300181, PMCID: PMC8366569, DOI: 10.1038/s41379-020-0544-x.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerNegative breast cancerOverall percent agreementPD-L1Intraclass correlation coefficientBreast cancerAdvanced triple-negative breast cancerPD-L1 positive casesImmune cell stainingMultiple pathologistsPD-L1 scoringMulti-institutional evaluationLung cancer studiesAtezolizumab therapySP142 assaySP263 assaysPatient selectionSP263SP142US FoodDrug AdministrationPathologist's assessmentPositive casesReal-world settingPercent agreementThe path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice
Gonzalez‐Ericsson P, Stovgaard ES, Sua LF, Reisenbichler E, Kos Z, Carter JM, Michiels S, Le Quesne J, Nielsen TO, Lænkholm A, Fox SB, Adam J, Bartlett JM, Rimm DL, Quinn C, Peeters D, Dieci MV, Vincent‐Salomon A, Cree I, Hida AI, Balko JM, Haynes HR, Frahm I, Acosta‐Haab G, Balancin M, Bellolio E, Yang W, Kirtani P, Sugie T, Ehinger A, Castaneda CA, Kok M, McArthur H, Siziopikou K, Badve S, Fineberg S, Gown A, Viale G, Schnitt SJ, Pruneri G, Penault‐Llorca F, Hewitt S, Thompson EA, Allison KH, Symmans WF, Bellizzi AM, Brogi E, Moore DA, Larsimont D, Dillon DA, Lazar A, Lien H, Goetz MP, Broeckx G, Bairi K, Harbeck N, Cimino‐Mathews A, Sotiriou C, Adams S, Liu S, Loibl S, Chen I, Lakhani SR, Juco JW, Denkert C, Blackley EF, Demaria S, Leon‐Ferre R, Gluz O, Zardavas D, Emancipator K, Ely S, Loi S, Salgado R, Sanders M, Group I. The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice. The Journal Of Pathology 2020, 250: 667-684. PMID: 32129476, DOI: 10.1002/path.5406.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerTumor-infiltrating lymphocytesPD-L1Breast cancerPatient selectionInter-reader reproducibilityEarly-stage triple-negative breast cancerPD-1/PD-L1 inhibitorsStage triple-negative breast cancerAdvanced triple-negative breast cancerPD-1/PD-L1High tumor-infiltrating lymphocytesImmune checkpoint inhibitor therapyAddition of atezolizumabPD-L1 assessmentSuboptimal patient selectionCheckpoint inhibitor therapyOptimal patient selectionPD-L1 expressionPD-L1 inhibitorsDaily practiceStandard of careImmuno-therapeutic approachesNegative breast cancerEosin-stained slides
2018
Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer
Altan M, Kidwell KM, Pelekanou V, Carvajal-Hausdorf DE, Schalper KA, Toki MI, Thomas DG, Sabel MS, Hayes DF, Rimm DL. Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer. Npj Breast Cancer 2018, 4: 40. PMID: 30564631, PMCID: PMC6288133, DOI: 10.1038/s41523-018-0095-1.Peer-Reviewed Original ResearchPD-L1 expressionBreast cancer intrinsic subtypesB7-H4Clinico-pathological variablesB7-H4 proteinPD-L1Breast cancerIntrinsic subtypesB7-H4 protein expressionCD28/B7 familyTumor PD-L1 expressionQuantitative immunofluorescenceTriple-negative breast cancerRelationship of tumorCo-inhibitory moleculesImmune checkpoint inhibitorsClinico-pathological characteristicsFraction of patientsNegative breast cancerTissue microarray formatBreast cancer casesPD-L1 proteinCheckpoint inhibitorsClinical benefitExclusive patternPrognostic 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 Research
2012
Hypoxia-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
2009
DNA Hypermethylation of ESR1 and PGR in Breast Cancer: Pathologic and Epidemiologic Associations
Gaudet MM, Campan M, Figueroa JD, Yang XR, Lissowska J, Peplonska B, Brinton LA, Rimm DL, Laird PW, Garcia-Closas M, Sherman ME. DNA Hypermethylation of ESR1 and PGR in Breast Cancer: Pathologic and Epidemiologic Associations. Cancer Epidemiology Biomarkers & Prevention 2009, 18: 3036-3043. PMID: 19861523, PMCID: PMC2783691, DOI: 10.1158/1055-9965.epi-09-0678.Peer-Reviewed Original ResearchConceptsBreast cancerPopulation-based case-control studyBreast cancer risk factorsPromoter CLevels of ERalphaPR-negative tumorsInvasive breast cancerCancer risk factorsCase-control studyPercentage of tumorsNegative breast cancerTumor tissue coresImproved risk predictionLower ERalphaTumor characteristicsPR expressionProgesterone receptorEpidemiologic associationRisk factorsInverse associationDNA hypermethylationPR levelsMost tumorsReceptor silencingTumors