2023
Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis
Loi S, Salgado R, Schmid P, Cortes J, Cescon D, Winer E, Toppmeyer D, Rugo H, De Laurentiis M, Nanda R, Iwata H, Awada A, Tan A, Sun Y, Karantza V, Wang A, Huang L, Saadatpour A, Cristescu R, Yearley J, Lunceford J, Jelinic P, Adams S. Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis. JCO Precision Oncology 2023, 7: e2200317. PMID: 37099733, DOI: 10.1200/po.22.00317.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorHumansTriple Negative Breast NeoplasmsConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerClinical outcomesPembrolizumab monotherapyPD-L1Metastatic diseaseGEP signaturesBreast cancerStromal tumor-infiltrating lymphocytesT-cell-inflamed gene expression profileExploratory biomarker analysisMore systemic therapiesPD-L1 CPSTumor PD-L1PD-L1 statusTumor-infiltrating lymphocytesImproved clinical outcomesTumor mutational burdenSignature 3Mutational signature 3Cohort BDifferentiation 8Systemic therapyCohort ACombined cohort
2021
Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial
Tolaney SM, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Briccetti F, Schneider B, Garrett AM, Marcom K, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu M, Ruddy K, Zheng Y, Rosenberg SM, Gelber RD, Trippa L, Barry W, DeMeo M, Burstein H, Partridge A, Winer EP, Krop I. Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial. Journal Of Clinical Oncology 2021, 39: 2375-2385. PMID: 34077270, DOI: 10.1200/jco.20.03398.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDisease-Free SurvivalFemaleHumansMiddle AgedNeoplasm StagingPaclitaxelTrastuzumabConceptsInvasive disease-free survivalT-DM1Breast cancerStage IStage I HER2-positive breast cancerHER2-positive breast cancerHuman epidermal growth factor receptorAdjuvant T-DM1Co-primary objectivesDisease-free survivalPatient-reported outcomesEpidermal growth factor receptorGrowth factor receptorProtocol therapyAnalysis populationTrastuzumab emtansineClinical trialsRelevant toxicityPatientsFactor receptorLess toxicityWeeksTrastuzumabCancerPaclitaxelUpdated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological Complete Response to Pertuzumab and Trastuzumab in Breast Cancer
Connolly RM, Leal JP, Solnes L, Huang CY, Carpenter A, Gaffney K, Abramson V, Carey LA, Liu MC, Rimawi M, Specht J, Storniolo AM, Valero V, Vaklavas C, Krop IE, Winer EP, Camp M, Miller RS, Wolff AC, Cimino-Mathews A, Park BH, Wahl RL, Stearns V. Updated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological Complete Response to Pertuzumab and Trastuzumab in Breast Cancer. Journal Of Clinical Oncology 2021, 39: 2247-2256. PMID: 33999652, PMCID: PMC8260904, DOI: 10.1200/jco.21.00280.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantFemaleFluorodeoxyglucose F18HumansMiddle AgedNeoadjuvant TherapyPositron Emission Tomography Computed TomographyPredictive Value of TestsRadiopharmaceuticalsReceptor, ErbB-2Time FactorsTrastuzumabTreatment OutcomeUnited StatesConceptsPositron emission tomography-computed tomographyFluorodeoxyglucose positron emission tomography-computed tomographyHER2-positive breast cancerEmission tomography-computed tomographyPathologic complete responseTomography-computed tomographyStandardized uptake valueBreast cancerComplete responseUptake valuePercent changeOne-sided type ITumor maximum standardized uptake valueHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Maximum standardized uptake valuePathological complete responseGrowth factor receptor 2Median percent reductionPositive breast cancerTailoring of therapyLean body massReceiver operator characteristic analysisFactor receptor 2Operator characteristic analysisImpact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab
Filho OM, Viale G, Stein S, Trippa L, Yardley DA, Mayer IA, Abramson VG, Arteaga CL, Spring LM, Waks AG, Wrabel E, DeMeo MK, Bardia A, Dell'Orto P, Russo L, King TA, Polyak K, Michor F, Winer EP, Krop IE. Impact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab. Cancer Discovery 2021, 11: candisc.1557.2020. PMID: 33941592, PMCID: PMC8598376, DOI: 10.1158/2159-8290.cd-20-1557.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFemaleHumansMiddle AgedNeoadjuvant TherapyReceptor, ErbB-2TrastuzumabTreatment OutcomeConceptsHER2-positive breast cancerHER2 heterogeneityBreast cancerEarly-stage HER2-positive breast cancerHER2-positive early-stage breast cancerTherapeutic resistancePathologic complete response rateEarly-stage breast cancerNeoadjuvant clinical trialsComplete response rateSubset of patientsHER2 therapyPretreatment biopsiesEvaluable casesCure rateT-DM1Trastuzumab emtansineClinical trialsTreatment strategiesTreatment responseTreatment selectionResponse rateRelated commentaryTherapyIssue featureThe impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2-positive breast cancer
Janiszewska M, Stein S, Filho O, Eng J, Kingston NL, Harper NW, Rye IH, Alečković M, Trinh A, Murphy KC, Marangoni E, Cristea S, Oakes B, Winer EP, Krop I, Russnes HG, Spellman PT, Bucher E, Hu Z, Chin K, Gray JW, Michor F, Polyak K. The impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2-positive breast cancer. JCI Insight 2021, 6: e147617. PMID: 33886505, PMCID: PMC8262355, DOI: 10.1172/jci.insight.147617.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDNA Copy Number VariationsDrug Resistance, NeoplasmEpithelial CellsFemaleFibroblastsHumansMacrophagesMiddle AgedMutationNeoplasm TransplantationReceptor, ErbB-2TrastuzumabTumor MicroenvironmentVesicular Transport ProteinsConceptsBreast cancerTherapeutic resistanceHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Patient-derived xenograft modelsLymphatic vessel endothelial hyaluronan receptorHER2-targeted therapiesGrowth factor receptor 2Impact of tumorFibroblastic reticular cellsFactor receptor 2Tumor epithelial cellsIntratumor heterogeneityDivergent cellular phenotypesResistance-conferring mutationsClinical outcomesPIK3CA mutationsTreatment responseClinical challengeDifferent therapiesFrequency of cellsXenograft modelReceptor 2Stromal determinantsPhysical Activity, Weight, and Outcomes in Patients Receiving Chemotherapy for Metastatic Breast Cancer (C40502/Alliance)
Ligibel JA, Huebner L, Rugo HS, Burstein HJ, Toppmeyer DL, Anders CK, Ma C, Barry WT, Suman V, Carey LA, Partridge AH, Hudis CA, Winer EP. Physical Activity, Weight, and Outcomes in Patients Receiving Chemotherapy for Metastatic Breast Cancer (C40502/Alliance). JNCI Cancer Spectrum 2021, 5: pkab025-. PMID: 33981951, PMCID: PMC8103727, DOI: 10.1093/jncics/pkab025.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBody HeightBody Mass IndexBody WeightBreast NeoplasmsEpothilonesExerciseFemaleHumansMiddle AgedObesityPaclitaxelProgression-Free SurvivalProportional Hazards ModelsTreatment OutcomeYoung AdultConceptsProgression-free survivalMetastatic breast cancerBody mass indexOverall survivalPhysical activityBreast cancerMass indexMET hoursFirst-line taxane-based chemotherapyHormone receptor-positive cancersBaseline body mass indexFirst-line chemotherapyTaxane-based chemotherapyReceptor-positive cancersRecreational physical activityRates of obesityMetastatic diseaseCox modelingMedian ageOverall mortalityRandomized trialsTask hoursMetabolic equivalentsPatientsCancer
2020
A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer
Barroso-Sousa R, Krop IE, Trippa L, Tan-Wasielewski Z, Li T, Osmani W, Andrews C, Dillon D, Richardson ET, Pastorello RG, Winer EP, Mittendorf EA, Bellon JR, Schoenfeld JD, Tolaney SM. A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer. Clinical Breast Cancer 2020, 20: 238-245. PMID: 32113750, DOI: 10.1016/j.clbc.2020.01.012.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBiomarkers, TumorBreastBreast NeoplasmsCarcinoma, Ductal, BreastChemoradiotherapyDrug Administration ScheduleFemaleHumansInfusions, IntravenousMiddle AgedPalliative CareProgrammed Cell Death 1 ReceptorProgression-Free SurvivalReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneResponse Evaluation Criteria in Solid TumorsConceptsMetastatic breast cancerHormone receptor-positive metastatic breast cancerProgression-free survivalRadiation therapyObjective responseOverall survivalBreast cancerResponse rateMedian progression-free survivalCause adverse eventsGrade 3 eventsMedian prior linesMedian overall survivalObjective response ratePalliative radiation therapyPhase II studyTumor-infiltrating lymphocytesLymph node lesionsOverall response rateEpidermal growth factor receptorEligible patientsExploratory endpointsGrowth factor receptorPalliative radiotherapyPrimary endpoint
2016
Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer
Varadan V, Gilmore H, Miskimen KL, Tuck D, Parsai S, Awadallah A, Krop IE, Winer EP, Bossuyt V, Somlo G, Abu-Khalaf MM, Fenton MA, Sikov W, Harris L. Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer. Clinical Cancer Research 2016, 22: 3249-3259. PMID: 26842237, PMCID: PMC5439498, DOI: 10.1158/1078-0432.ccr-15-2021.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminsAntineoplastic Agents, ImmunologicalBiomarkers, TumorB-LymphocytesBreast NeoplasmsFemaleGene Expression ProfilingHumansImmunity, InnateLymphocyte ActivationMacrophagesMiddle AgedNeoadjuvant TherapyPaclitaxelProgrammed Cell Death 1 ReceptorReceptor, ErbB-2T-Lymphocytes, Helper-InducerTrastuzumabTreatment OutcomeConceptsPathologic complete responseBreast cancerImmune indicesBrief exposureFollicular helper T (Tfh) cell signatureHER2-positive breast cancerPD-1 positivitySingle-agent trastuzumabTrastuzumab-based therapyT cell activityT-cell signatureImmune cell infiltrationTumor core biopsiesImmune cell activationPreoperative trastuzumabNab-paclitaxelAntitumor immunityImmune signaturesPCR rateComplete responseMulticenter trialPD-1Cell infiltrationCore biopsyIntrinsic subtypes