2023
Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer
Tarantino P, Gupta H, Hughes M, Files J, Strauss S, Kirkner G, Feeney A, Li Y, Garrido-Castro A, Barroso-Sousa R, Bychkovsky B, DiLascio S, Sholl L, MacConaill L, Lindeman N, Johnson B, Meyerson M, Jeselsohn R, Qiu X, Li R, Long H, Winer E, Dillon D, Curigliano G, Cherniack A, Tolaney S, Lin N. Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer. Nature Communications 2023, 14: 7496. PMID: 37980405, PMCID: PMC10657399, DOI: 10.1038/s41467-023-43324-w.Peer-Reviewed Original ResearchConceptsHER2-low tumorsBreast cancerHER2-negative metastatic breast cancerMetastatic breast cancerTumor mutational burdenHigh rateComprehensive genomic characterizationHER2 0Mutational burdenBreast tumorsTumorsHER2Genomic alterationsNext-generation sequencingSignificant differencesGenomic findingsCancerGenomic landscapeMolecular underpinningsHemideletionGenomic characterizationHigher numberPatientsCopy countsAssociation 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 ResearchConceptsMetastatic 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
2022
Multidimensional Molecular Profiling of Metastatic Triple-Negative Breast Cancer and Immune Checkpoint Inhibitor Benefit.
Barroso-Sousa R, Forman J, Collier K, Weber ZT, Jammihal TR, Kao KZ, Richardson ET, Keenan T, Cohen O, Manos MP, Brennick RC, Ott PA, Hodi FS, Dillon DA, Attaya V, O'Meara T, Lin NU, Van Allen EM, Rodig S, Winer EP, Mittendorf EA, Wu CJ, Wagle N, Stover DG, Shukla SA, Tolaney SM. Multidimensional Molecular Profiling of Metastatic Triple-Negative Breast Cancer and Immune Checkpoint Inhibitor Benefit. JCO Precision Oncology 2022, 6: e2100413. PMID: 35797509, PMCID: PMC9848556, DOI: 10.1200/po.21.00413.Peer-Reviewed Original ResearchConceptsGene expression pathwaysMetastatic triple-negative breast cancerExpression pathwaysWhole-exome sequencingFollicular helper T cellsDNA damage repair pathwaysTriple-negative breast cancerProgression-free survivalMemory T cellsDamage repair pathwaysHelper T cellsTumor mutational burdenT cellsClonal evolutionOverall survivalDNA whole-exome sequencingTranscriptomic landscapeHomologous recombinationRepair pathwaysRNA sequencingM1 macrophagesBreast cancerDefective repairMutational burdenDNA damage
2021
Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study
Barroso-Sousa R, Keenan TE, Li T, Tayob N, Trippa L, Pastorello RG, Richardson III ET, Dillon D, Amoozgar Z, Overmoyer B, Schnitt SJ, Winer EP, Mittendorf EA, Van Allen E, Duda DG, Tolaney SM. Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study. Npj Breast Cancer 2021, 7: 110. PMID: 34433812, PMCID: PMC8387440, DOI: 10.1038/s41523-021-00287-9.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerTumor-infiltrating lymphocytesTriple-negative breast cancerObjective response ratePD-L1Primary endpointBreast cancerSingle-arm phase II studyHigh tumor-infiltrating lymphocytesLow tumor mutational burdenSafety of cabozantinibPhase II studyImmune checkpoint moleculesHigher pretreatment levelsTumor mutational burdenImmune gene expressionRECIST 1.1Checkpoint moleculesII studyImmunosuppressive cytokinesPartial responseNegative tumorsPositive tumorsTumor immunosuppressionRapid progression
2020
Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer
Tolaney SM, Barroso-Sousa R, Keenan T, Li T, Trippa L, Vaz-Luis I, Wulf G, Spring L, Sinclair NF, Andrews C, Pittenger J, Richardson ET, Dillon D, Lin NU, Overmoyer B, Partridge AH, Van Allen E, Mittendorf EA, Winer EP, Krop IE. Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer. JAMA Oncology 2020, 6: 1598-1605. PMID: 32880602, PMCID: PMC7489368, DOI: 10.1001/jamaoncol.2020.3524.Peer-Reviewed Original ResearchConceptsProgression-free survivalObjective response rateTumor-infiltrating lymphocytesTumor mutational burdenPD-L1 statusOverall survivalHormonal therapyPrior linesPD-L1Clinical trialsMedian numberDay 1Cell death ligand 1 (PD-L1) inhibitorsERBB2-negative metastatic breast cancerMedian progression-free survivalDeath ligand 1 (PD-L1) inhibitorsEnd pointCause adverse eventsEfficacy of eribulinHormone receptor positiveMulticenter phase 2PD-L1 22C3Treatment-related deathsLines of chemotherapyPrimary end pointTumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer
Barroso-Sousa R, Keenan TE, Pernas S, Exman P, Jain E, Garrido-Castro AC, Hughes M, Bychkovsky B, Umeton R, Files JL, Lindeman NI, MacConaill LE, Hodi FS, Krop IE, Dillon D, Winer EP, Wagle N, Lin NU, Mittendorf EA, Van Allen EM, Tolaney SM. Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer. Clinical Cancer Research 2020, 26: 2565-2572. PMID: 32019858, PMCID: PMC7269810, DOI: 10.1158/1078-0432.ccr-19-3507.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerHigh tumor mutational burdenProgression-free survivalTumor mutational burdenObjective response rateImmune checkpoint inhibitorsAnti-PD-1/L1 therapyTriple-negative breast cancerOverall survivalL1 therapyPD-L1Breast cancerMutational burdenLow objective response rateLonger progression-free survivalShorter progression-free survivalDana-Farber Cancer InstituteTumor genomic featuresShorter overall survivalMutations/megabaseCheckpoint inhibitorsVisceral metastasesL1 blockadePerformance statusPrior linesAssociation of tumor mutational burden (TMB) and clinical outcomes with pembrolizumab (pembro) versus chemotherapy (chemo) in patients with metastatic triple-negative breast cancer (mTNBC) from KEYNOTE-119.
Winer E, Lipatov O, Im S, Goncalves A, Muñoz-Couselo E, Lee K, Schmid P, Testa L, Witzel I, Ohtani S, Lunceford J, Karantza V, Mejia J, Cristescu R, Aurora-Garg D, Jelinic P, Huang L, Cortes J. Association of tumor mutational burden (TMB) and clinical outcomes with pembrolizumab (pembro) versus chemotherapy (chemo) in patients with metastatic triple-negative breast cancer (mTNBC) from KEYNOTE-119. Journal Of Clinical Oncology 2020, 38: 1013-1013. DOI: 10.1200/jco.2020.38.15_suppl.1013.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerTumor mutational burdenMut/MbClinical outcomesTriple-negative breast cancerChemo-treated patientsPrior systemic treatmentThird-line settingOverall study populationNumber of patientsTwo-sided p valuePD-L1 enrichmentReceiver operator characteristic analysisEstimates of efficacyOperator characteristic analysisP-valueFoundationOne CDxBaseline characteristicsMetastatic diseaseSystemic treatmentPotential positive associationTreatment armsClinical benefitCox regressionBreast cancer
2019
Nimbus: A phase II study of nivolumab plus ipilimumab in metastatic hypermutated HER2-negative breast cancer.
Barroso-Sousa R, Trippa L, Lange P, Andrews C, McArthur H, Haley B, Rugo H, Emens L, Winer E, Mittendorf E, Tolaney S. Nimbus: A phase II study of nivolumab plus ipilimumab in metastatic hypermutated HER2-negative breast cancer. Journal Of Clinical Oncology 2019, 37: tps1115-tps1115. DOI: 10.1200/jco.2019.37.15_suppl.tps1115.Peer-Reviewed Original ResearchMetastatic breast cancerTumor mutational burdenHER2-negative breast cancerBreast cancerResponse rateObjective responseTrue response rateMetastatic HER2-negative breast cancerHER2-negative metastatic breast cancerFurther studiesCombination of nivolumabEfficacy of nivolumabPhase 2 studyPhase II studyProgression-free survivalOverall response rateMut/MbMutations/megabaseCancer gene panelRECIST 1.1II studyOverall survivalPrior linesPeripheral bloodDisease progressionTUMOR MUTATIONAL BURDEN (TMB) IS A POTENTIAL PREDICTOR OF RESPONSE TO IMMUNE CHECKPOINT INHIBITORS (ICI) IN METASTATIC TRIPLE-NEGATIVE BREAST CANCER (MTNBC)
Sousa R, Tyekucheva S, Exman P, Umeton R, Hodi F, Winer E, Lin N, Tolaney S. TUMOR MUTATIONAL BURDEN (TMB) IS A POTENTIAL PREDICTOR OF RESPONSE TO IMMUNE CHECKPOINT INHIBITORS (ICI) IN METASTATIC TRIPLE-NEGATIVE BREAST CANCER (MTNBC). 2019, 5-5. DOI: 10.29289/259453942019v29s1g04.Peer-Reviewed Original Research