2021
Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer
Keenan TE, Guerriero JL, Barroso-Sousa R, Li T, O’Meara T, Giobbie-Hurder A, Tayob N, Hu J, Severgnini M, Agudo J, Vaz-Luis I, Anderson L, Attaya V, Park J, Conway J, He MX, Reardon B, Shannon E, Wulf G, Spring LM, Jeselsohn R, Krop I, Lin NU, Partridge A, Winer EP, Mittendorf EA, Liu D, Van Allen EM, Tolaney SM. Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer. Nature Communications 2021, 12: 5563. PMID: 34548479, PMCID: PMC8455578, DOI: 10.1038/s41467-021-25769-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntigen PresentationAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBreast NeoplasmsCytokinesDrug Resistance, NeoplasmEstrogensFemaleFuransGene Expression ProfilingGenetic HeterogeneityGenome, HumanGenomicsHumansImmune Checkpoint InhibitorsKetonesLymphocytes, Tumor-InfiltratingMaleMiddle AgedMutationNeoplasm MetastasisReceptors, EstrogenReceptors, ProgesteroneSignal TransductionSurvival RateTreatment OutcomeConceptsImmune checkpoint inhibitorsBreast cancerHormone receptor-positive metastatic breast cancerHormone receptor-positive breast cancerFinal overall survival resultsRandomized phase 2 trialReceptor-positive breast cancerMinimal therapeutic effectPhase 2 trialMetastatic breast cancerOverall survival resultsPre-treatment tumorsCheckpoint inhibitorsCytokine changesICI responseCombination therapyImmune infiltrationImmunoregulatory cytokinesSurvival resultsAntigen presentationTherapeutic effectTherapeutic validationCancerMolecular correlatesTumor heterogeneity
2018
Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis
Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, Tolaney SM. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncology 2018, 4: 173-182. PMID: 28973656, PMCID: PMC5838579, DOI: 10.1001/jamaoncol.2017.3064.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsCTLA-4 inhibitorsPD-L1 inhibitorsPrimary adrenal insufficiencyInsulin-deficient diabetesAdverse eventsCombination therapyEndocrine dysfunctionSystematic reviewAdrenal insufficiencyPD-1Clinical trialsDifferent immune checkpoint inhibitorsIncidence of AEsImmune checkpoint inhibitorsAdvanced solid tumorsEndocrine adverse eventsRisk of hyperthyroidismSuch adverse eventsPreferred Reporting ItemsRandom-effects modelGrade hypothyroidismInhibitor regimensMDX-010Checkpoint inhibitors
2017
CMET-25. PROGRESSION-FREE SURVIVAL (PFS) AND SITE OF FIRST PROGRESSION IN HER2+ METASTATIC BREAST CANCER PATIENTS WITH OR WITHOUT BRAIN METASTASES: A POOLED ANALYSIS OF TUCATINIB PHASE I STUDIES
Hamilton E, Moulder S, Ferrario C, Conlin A, Krop I, Chamberlain M, Gray T, Borges V. CMET-25. PROGRESSION-FREE SURVIVAL (PFS) AND SITE OF FIRST PROGRESSION IN HER2+ METASTATIC BREAST CANCER PATIENTS WITH OR WITHOUT BRAIN METASTASES: A POOLED ANALYSIS OF TUCATINIB PHASE I STUDIES. Neuro-Oncology 2017, 19: vi44-vi44. PMCID: PMC5692086, DOI: 10.1093/neuonc/nox168.173.Peer-Reviewed Original ResearchProgression-free survivalBaseline brain metastasesMetastatic breast cancerBrain metastasesMedian progression-free survivalMetastatic breast cancer patientsPhase 1b studyProgressive brain metastasesStable brain metastasesSite of relapseIncidence of progressionSignificant neurologic morbidityUntreated brain metastasesBreast cancer patientsTyrosine kinase inhibitorsBM cohortHER2 therapyHER2CLIMB trialPrior HER2Neurologic morbidityDurable responsesFirst progressionSystemic metastasesCombination therapyPatient cohort
2015
PIK3CAH1047R- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling
Cheng H, Liu P, Ohlson C, Xu E, Symonds L, Isabella A, Muller WJ, Lin NU, Krop IE, Roberts TM, Winer EP, Arteaga CL, Zhao JJ. PIK3CAH1047R- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling. Oncogene 2015, 35: 2961-2970. PMID: 26640141, PMCID: PMC4896860, DOI: 10.1038/onc.2015.377.Peer-Reviewed Original ResearchConceptsBreast cancerPIK3CA mutationsMammary tumorsHER2 amplification/overexpressionHER2-positive breast cancerHER2-positive cancersPrimary mammary tumorsHER2/HER3PIK3CA-activating mutationsHER2/neuHuman breast cancerEffective treatment approachAmplification/overexpressionCompound mouse modelMEK-ERK signalingMouse mammary glandWorse prognosisCombination therapyMammary tumorigenesisMouse modelMutant PIK3CATreatment approachesHER2Combined inhibitionCompensatory activationRole of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients
Tolaney SM, Boucher Y, Duda DG, Martin JD, Seano G, Ancukiewicz M, Barry WT, Goel S, Lahdenrata J, Isakoff SJ, Yeh ED, Jain SR, Golshan M, Brock J, Snuderl M, Winer EP, Krop IE, Jain RK. Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 14325-14330. PMID: 26578779, PMCID: PMC4655544, DOI: 10.1073/pnas.1518808112.Peer-Reviewed Original ResearchConceptsPathologic complete responseBreast cancer patientsMicrovascular densityInterstitial fluid pressureNeoadjuvant bevacizumabBevacizumab monotherapyPathologic responseCancer patientsImproved pathologic responsePhase II studyPotential predictive biomarkersHER2-negative BCBasal-like subtypePreoperative bevacizumabPaclitaxel chemotherapyII studyComplete responseCombination therapyPredictive biomarkersPlasma biomarkersVascular normalizationBevacizumabVascular densityNew therapiesTissue biopsies