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 range
2021
What if the future of HER2‐positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study
Pizzamiglio S, Cosentino G, Ciniselli CM, De Cecco L, Cataldo A, Plantamura I, Triulzi T, El‐abed S, Wang Y, Bajji M, Nuciforo P, Huober J, Ellard SL, Rimm DL, Gombos A, Daidone MG, Verderio P, Tagliabue E, Di Cosimo S, Iorio MV. What if the future of HER2‐positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study. Cancer Medicine 2021, 11: 332-339. PMID: 34921525, PMCID: PMC8729061, DOI: 10.1002/cam4.4449.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancer patientsEvent-free survivalBreast cancer patientsNeoadjuvant therapyCancer patientsPathological complete response rateSingle-agent trastuzumabTwo-miRNA signatureComplete response rateDifferential clinical outcomesPredictive miRNA signatureTrastuzumab armBaseline biopsiesClinical outcomesPathological variablesPrognostic valueUnivariate analysisAgent trastuzumabPrognostic signatureResponse ratePatientsTissue miRNAsMiRNA expression profilesMiRNA signatureMultivariate modelInterplay 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 samplesCharacterization 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
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
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. 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 cohort
2015
High level PHGDH expression in breast is predominantly associated with keratin 5‐positive cell lineage independently of malignancy
Gromova I, Gromov P, Honma N, Kumar S, Rimm D, Talman ML, Wielenga VT, Moreira JM. High level PHGDH expression in breast is predominantly associated with keratin 5‐positive cell lineage independently of malignancy. Molecular Oncology 2015, 9: 1636-1654. PMID: 26026368, PMCID: PMC5528790, DOI: 10.1016/j.molonc.2015.05.003.Peer-Reviewed Original ResearchConceptsOverexpression of PhgdhPHGDH expressionMammary epithelial cellsTriple-negative breast cancer patientsNegative breast cancer patientsEpithelial cellsBreast cancer patientsNormal breast tissueCell lineagesMammary tissue samplesHigh-level expressionExpression of PHGDHProspective cohortCancer patientsCK5-positive cellsBasal phenotypeProteomic profilingTNBC samplesIHC analysisQuantitative IHC analysisCancer typesBreast tissueMalignancyCandidate oncogeneOncogenic functionPD-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
Quantitative assessment of miR34a as an independent prognostic marker in breast cancer
Agarwal S, Hanna J, Sherman ME, Figueroa J, Rimm DL. Quantitative assessment of miR34a as an independent prognostic marker in breast cancer. British Journal Of Cancer 2014, 112: 61-68. PMID: 25474246, PMCID: PMC4453614, DOI: 10.1038/bjc.2014.573.Peer-Reviewed Original ResearchConceptsDisease-specific survivalBreast cancer cohortPoor disease-specific survivalDisease-specific deathIndependent breast cancer cohortsBreast cancerCancer cohortPoor outcomeCohort 1Multivariate Cox proportional hazards analysisCox proportional hazards analysisNode-positive populationX-tile softwareNode-negative patientsProportional hazards analysisTumor suppressorBreast cancer patientsIndependent prognostic markerExpression of miR34aReceptor statusNode statusPreclinical observationsTumor sizeCancer patientsCohort 2In Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients
Vassilakopoulou M, Togun T, Dafni U, Cheng H, Bordeaux J, Neumeister VM, Bobos M, Pentheroudakis G, Skarlos DV, Pectasides D, Kotoula V, Fountzilas G, Rimm DL, Psyrri A. In Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients. PLOS ONE 2014, 9: e99131. PMID: 24968015, PMCID: PMC4072595, DOI: 10.1371/journal.pone.0099131.Peer-Reviewed Original ResearchConceptsBreast cancer patientsMetastatic breast cancer patientsFISH HER2Cancer patientsHER2 mRNAPrognostic factorsTrastuzumab-treated metastatic breast cancer patientsMultivariate Cox regression modelECD HER2Log rank pMetastatic breast cancerStrong prognostic factorCox regression modelKaplan-Meier estimatesHER2 mRNA levelsHER2-ICDChemotherapy regimensMetastatic cohortTrastuzumab treatmentBreast cancerTissue microarrayMRNA statusPerformance of markersHER2 receptorPredictive valueQuantitative 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
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 patientsQuantitative 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 patientsA pilot chemoprevention study of isopropanolic black cohosh extract in women with ductal carcinoma in situ.
Hofstatter E, Stavris K, Horowitz N, Killelea B, Tsangaris T, Lannin D, Andrejeva L, Cong X, Yao X, Rimm D, Chagpar A. A pilot chemoprevention study of isopropanolic black cohosh extract in women with ductal carcinoma in situ. Journal Of Clinical Oncology 2013, 31: tps1609-tps1609. DOI: 10.1200/jco.2013.31.15_suppl.tps1609.Peer-Reviewed Original ResearchIsopropanolic black cohosh extractBlack cohosh extractBlack cohoshDuctal carcinomaBreast cancerBreast epithelial cell proliferationPre-operative courseTwo-sided significance levelDisease-free survivalLiver function testsBreast cancer preventionSerum hormone levelsAnti-inflammatory effectsBreast cancer patientsPost-menopausal womenCohort of womenRecent preclinical dataSignificant protective effectKi-67 stainingBreast core biopsyLevels of Ki67Years of ageEpithelial cell proliferationWilcoxon signed-rank testEligible subjects
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 recombinationIn situ quantitative measurement of mRNA to predict response to trastuzumab in a cohort of metastatic breast cancer patients.
Vassilakopoulou M, Bordeaux J, Neumeister V, Cheng H, Schalper K, Skarlos D, Pectasides D, Pavlidis N, Koutras A, Linardou H, Razis E, Bobos M, Kotoula V, Rimm D, Fountzilas G, Psyrri A. In situ quantitative measurement of mRNA to predict response to trastuzumab in a cohort of metastatic breast cancer patients. Journal Of Clinical Oncology 2012, 30: 573-573. DOI: 10.1200/jco.2012.30.15_suppl.573.Peer-Reviewed Original ResearchBreast cancer patientsMetastatic breast cancer patientsCancer patientsHER2 mRNA levelsHER2 mRNAHistological gradeTrastuzumab-treated metastatic breast cancer patientsMultivariate analysisCox proportional hazards modelHormone receptor statusMetastatic breast cancerKaplan-Meier analysisOverall survival timeMRNA levelsProportional hazards modelHER2 extracellular domainAssessment of HER2Extracellular domainTrastuzumab initiationChemotherapy regimensPrimary endpointReceptor statusTrastuzumab therapyMetastatic cohortTrastuzumab treatmentCan primary tumor markers of cancer-initiating cells predict lymph node positivity in breast cancer patients?
Chagpar A, Neumeister V, Lannin D, Rimm D. Can primary tumor markers of cancer-initiating cells predict lymph node positivity in breast cancer patients? Journal Of Clinical Oncology 2012, 30: 1121-1121. DOI: 10.1200/jco.2012.30.15_suppl.1121.Peer-Reviewed Original ResearchBreast cancer patientsLN statusCancer patientsLymphovascular invasionTumor sizeTumor markersPositive LNsPoor prognosisMedian numberPrimary tumor markersMedian patient ageMedian tumor sizeLymph node positivityLN-positive patientsLymph node statusOnly factorCancer initiating cellsCancer-initiating cellsLevels of CD44Axillary surgeryLN positivityNode positivityPatient agePositive patientsClinicopathologic dataLow levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes
Peck AR, Witkiewicz AK, Liu C, Klimowicz AC, Stringer GA, Pequignot E, Freydin B, Yang N, Ertel A, Tran TH, Girondo MA, Rosenberg AL, Hooke JA, Kovatich AJ, Shriver CD, Rimm DL, Magliocco AM, Hyslop T, Rui H. Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes. Breast Cancer Research 2012, 14: r130. PMID: 23036105, PMCID: PMC4053108, DOI: 10.1186/bcr3328.Peer-Reviewed Original ResearchConceptsPoor prognosisBreast cancerClinical outcomesIndependent markerNode-negative breast cancer patientsNode-negative breast cancerLower tumor levelsPrimary breast cancerUnfavorable clinical outcomeBreast cancer patientsClinical outcome dataProtein levelsRandomized clinical trialsPredictors of responseNew independent markerBreast cancer progressionTherapy-naïveFourfold riskCancer patientsTherapy failureTumor levelsArchival cohortUnfavorable outcomeClinical trialsStat5a/bQuantitative assessment of invasive mena isoforms (Menacalc) as an independent prognostic marker in breast cancer
Agarwal S, Gertler FB, Balsamo M, Condeelis JS, Camp RL, Xue X, Lin J, Rohan TE, Rimm DL. Quantitative assessment of invasive mena isoforms (Menacalc) as an independent prognostic marker in breast cancer. Breast Cancer Research 2012, 14: r124. PMID: 22971274, PMCID: PMC3962029, DOI: 10.1186/bcr3318.Peer-Reviewed Original ResearchConceptsBreast cancer cohortBreast cancerPoor outcomeTumor cellsCancer cohortPoor disease-specific survivalDisease-specific deathDisease-specific survivalBreast cancer patientsIndependent prognostic markerIndependent breast cancer cohortsNon-invasive tumor cellsInvasive tumor cellsReceptor statusNode statusTumor sizeCancer patientsPrognostic markerSignificant associationCohortCancerIsoform expressionPatientsMetastasisOutcomes
2011
P1-06-24: Nuclear Localization of Stat5a Predicts Response to Antiestrogen Therapy and Prognosis of Clinical Breast Cancer Outcome.
Peck A, Witkiewicz A, Liu C, Klimowicz A, Stringer G, Pequignot E, Freydin B, Yang N, Tran T, Rosenberg A, Hooke J, Kovatich A, Shriver C, Rimm D, Magliocco A, Hyslop T, Rui H. P1-06-24: Nuclear Localization of Stat5a Predicts Response to Antiestrogen Therapy and Prognosis of Clinical Breast Cancer Outcome. Cancer Research 2011, 71: p1-06-24-p1-06-24. DOI: 10.1158/0008-5472.sabcs11-p1-06-24.Peer-Reviewed Original ResearchCancer-specific survivalBreast cancer outcomesBreast cancer patientsAntiestrogen therapyClinical featuresCancer outcomesCancer patientsBreast cancerStandard immunohistochemistryNode-negative breast cancer patientsPathologist scoringPoor breast cancer outcomesBreast cancer-specific survivalQuantitative immunofluorescencePoor breast cancer prognosisInvasive breast cancer tissuesHormone receptor statusPredictors of responseFavorable prognostic markerBreast cancer prognosisBreast cancer tissuesNormal mammary developmentUseful clinical toolWhole tissue sectionsAntiestrogen response