2023
Image 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 correlation
2022
Prediction 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 cycle
2017
Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer
Dieci MV, Radosevic-Robin N, Fineberg S, van den Eynden G, Ternes N, Penault-Llorca F, Pruneri G, D’Alfonso T, Demaria S, Castaneda C, Sanchez J, Badve S, Michiels S, Bossuyt V, Rojo F, Singh B, Nielsen T, Viale G, Kim SR, Hewitt S, Wienert S, Loibl S, Rimm D, Symmans F, Denkert C, Adams S, Loi S, Salgado R, Cancer O. Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer. Seminars In Cancer Biology 2017, 52: 16-25. PMID: 29024776, DOI: 10.1016/j.semcancer.2017.10.003.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesBreast cancerResidual diseaseTIL assessmentDuctal carcinomaInternational Immuno-Oncology Biomarker Working GroupBiomarker Working GroupClinical breast cancer researchBreast cancer researchNeoadjuvant chemotherapyNeoadjuvant therapyImmunotherapeutic strategiesImmunological biomarkersInvasive carcinomaClinical trialsClinical relevanceConsensus guidanceInternational guidelinesCarcinomaWorking GroupCancerDiseaseMorphological evaluationLymphocytesCancer researchEffect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance
Pelekanou V, Carvajal-Hausdorf DE, Altan M, Wasserman B, Carvajal-Hausdorf C, Wimberly H, Brown J, Lannin D, Pusztai L, Rimm DL. Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance. Breast Cancer Research 2017, 19: 91. PMID: 28784153, PMCID: PMC5547502, DOI: 10.1186/s13058-017-0884-8.Peer-Reviewed Original ResearchConceptsStromal tumor-infiltrating lymphocytesPD-L1 expressionTumor-infiltrating lymphocytesRecurrence-free survivalNeoadjuvant chemotherapyResidual cancer tissueTIL countBreast cancerCancer tissuesDeath ligand 1 (PD-L1) protein expressionNode-positive breast cancerImproved recurrence-free survivalPD-L1 protein expressionHigher TIL countsPD-L1 statusProtein expressionBreast cancer patientsBreast cancer tissuesPost-treatment samplesPrechemotherapy samplesTIL infiltrationResidual cancerImmune markersResidual diseasePatient cohortEffects of neoadjuvant chemotherapy (NAC) on tumor infiltrating lymphocytes (TIL) and PD-L1 expression in the SWOG S0800 clinical trial.
Pelekanou V, Barlow W, von Wahlde M, Wasserman B, Lo Y, Hayes D, Hortobagyi G, Gralow J, Tripathy D, Livingston R, Porter P, Nahleh Z, Rimm D, Pusztai L. Effects of neoadjuvant chemotherapy (NAC) on tumor infiltrating lymphocytes (TIL) and PD-L1 expression in the SWOG S0800 clinical trial. Journal Of Clinical Oncology 2017, 35: 519-519. DOI: 10.1200/jco.2017.35.15_suppl.519.Peer-Reviewed Original ResearchPD-L1 expressionNeoadjuvant chemotherapyNAC armTIL countClinical trialsImmune parametersNAC samplesBaseline PD-L1 expressionPathologic complete response rateDose-dense doxorubicinComplete response ratePD-L1 immunohistochemistryHER2-negative casesMinority of casesNab-paclitaxelResidual diseaseMean changeResponse rateLogistic regressionTILsBaselineEpithelial cellsHigh PCRChemotherapyTumors
2016
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. 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 2016, 22: 1499-1509. PMID: 26515496, PMCID: PMC4794351, DOI: 10.1158/1078-0432.ccr-15-1125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-H1 AntigenBiomarkersCell Line, TumorDisease Models, AnimalDisease ProgressionFemaleGene Expression ProfilingHumansImmunomodulationImmunophenotypingLymphocytes, Tumor-InfiltratingMiceMitogen-Activated Protein KinasesMortalityPhenotypeProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsRas ProteinsSignal TransductionTranscriptomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerTumor-infiltrating lymphocytesImmune checkpoint inhibitorsResidual diseaseNeoadjuvant chemotherapyBreast cancerPD-L1Checkpoint inhibitorsMHC expressionMouse modelPD-1/PD-L1 immune checkpoint inhibitorsPD-L1 immune checkpoint inhibitorsPresence of TILsPD-1/PD-L1Low tumor-infiltrating lymphocytesPD-L1/PDAntitumor immune responseRAS/MAPK activationCell-surface MHC expressionMAPK activationImproved survivalImproved prognosisPredictive biomarkersClinical trialsImmune response