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 correlation
2021
Deep 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 standardImmunohistochemistryHematoxylinNeoadjuvant 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. Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer. Npj Breast Cancer 2021, 7: 9. PMID: 33558513, PMCID: PMC7870853, DOI: 10.1038/s41523-021-00219-7.Peer-Reviewed Original ResearchStromal tumor-infiltrating lymphocytesWeekly nab-paclitaxelTriple-negative breast cancerPD-L1Nab-paclitaxelAdverse eventsBreast cancerGrade 3/4 treatment-related adverse eventsPhase I/II trialGrade 3/4 adverse eventsTreatment-related adverse eventsDoxorubicin/cyclophosphamidePhase II studyGuillain-Barre syndromeMononuclear inflammatory cellsPathologic complete responseTumor-infiltrating lymphocytesTumor cell stainingEvaluable patientsNeoadjuvant durvalumabSP263 antibodyII trialNeoadjuvant chemotherapyNeoadjuvant therapyPrimary endpoint
2018
An 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
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 researchErratum to: Effect 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. Erratum to: Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance. Breast Cancer Research 2017, 19: 109. PMID: 28946899, PMCID: PMC5613519, DOI: 10.1186/s13058-017-0898-2.Peer-Reviewed Original 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
Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence
Balko JM, Schwarz LJ, Luo N, Estrada MV, Giltnane JM, Dávila-González D, Wang K, Sánchez V, Dean PT, Combs SE, Hicks D, Pinto JA, Landis MD, Doimi FD, Yelensky R, Miller VA, Stephens PJ, Rimm DL, Gómez H, Chang JC, Sanders ME, Cook RS, Arteaga CL. Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence. Science Translational Medicine 2016, 8: 334ra53. PMID: 27075627, PMCID: PMC5256931, DOI: 10.1126/scitranslmed.aad3001.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCell Line, TumorCell ProliferationChromosomes, Human, Pair 9Cohort StudiesFemaleGene AmplificationGene Knockdown TechniquesGenetic LociHumansJanus Kinase 2Middle AgedSignal TransductionSpheroids, CellularSTAT3 Transcription FactorSTAT6 Transcription FactorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerJAK2 amplificationBreast cancerUntreated triple-negative breast cancerEventual metastatic spreadBasal-like cancersBreast cancer subtypesTNBC cell linesAmplification of JAK2Janus kinase 2 (JAK2) geneNeoadjuvant chemotherapyOverall survivalTNBC xenograftsJAK1/2 inhibitorClinical trialsMetastatic spreadKinase 2 geneJAK2-specific inhibitorTumor growthCancer subtypesMammosphere formationPatientsPotential biomarkersTumor progressionJAK2 inhibitorsRAS/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
2015
PD-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 assessment of CD3, CD8, and CD20 in tumor-infiltrating lymphocytes and predictive value for response to neoadjuvant chemotherapy in breast cancer.
Brown J, Bai Y, Bossuyt V, Nixon C, Lannin D, Rimm D. Quantitative assessment of CD3, CD8, and CD20 in tumor-infiltrating lymphocytes and predictive value for response to neoadjuvant chemotherapy in breast cancer. Journal Of Clinical Oncology 2014, 32: 1027-1027. DOI: 10.1200/jco.2014.32.15_suppl.1027.Peer-Reviewed Original ResearchQuantitative 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 therapyPreoperative clinical trialPre-surgical settingSingle-agent trastuzumabPathologic complete responseInitiation of treatmentWeeks of treatmentBreast cancer patientsTumor core biopsiesCore biopsy samplesMonoclonal antibody trastuzumabEvaluable patientsNeoadjuvant regimenNeoadjuvant chemotherapyNeoadjuvant therapyNeoadjuvant treatmentComplete responsePreoperative setting
2013
Quantitative Ki-67 score as predictive of response to neoadjuvant chemotherapy in breast cancer.
Brown J, Lannin D, Killelea B, DiGiovanna M, Rimm D. Quantitative Ki-67 score as predictive of response to neoadjuvant chemotherapy in breast cancer. Journal Of Clinical Oncology 2013, 31: 1085-1085. DOI: 10.1200/jco.2013.31.15_suppl.1085.Peer-Reviewed Original ResearchKi-67 expressionPathological complete responseNeoadjuvant chemotherapyKi-67Consecutive invasive breast cancer patientsAQUA scoreInvasive breast cancer patientsAdditional survival benefitBreast cancer patientsKi-67 levelsPre-surgical biopsyKi-67 scoreLikelihood of responseMIB-1 antibodyPrediction of responseNeoadjuvant therapyComplete responseNodal statusSurvival benefitER statusIndependent predictorsMultivariable analysisAdvanced tumorsTumor sizeCancer patients