2024
Endocrine-Sensitive Disease Rate in Postmenopausal Patients With Estrogen Receptor–Rich/ERBB2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, or Their Combination
X. C, Suman V, Sanati S, Vij K, Anurag M, Leitch A, Unzeitig G, Hoog J, Fernandez-Martinez A, Fan C, Gibbs R, Watson M, Dockter T, Hahn O, Guenther J, Caudle A, Crouch E, Tiersten A, Mita M, Razaq W, Hieken T, Wang Y, Rimawi M, Weiss A, Winer E, Hunt K, Perou C, Ellis M, Partridge A, Carey L. Endocrine-Sensitive Disease Rate in Postmenopausal Patients With Estrogen Receptor–Rich/ERBB2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, or Their Combination. JAMA Oncology 2024, 10: 362-371. PMID: 38236590, PMCID: PMC10797521, DOI: 10.1001/jamaoncol.2023.6038.Peer-Reviewed Original ResearchConceptsNeoadjuvant endocrine therapyBreast cancerWeek 4Neoadjuvant chemotherapyPostmenopausal womenPAM50 subtypesNonluminal tumorsClinical stage II to IIIRate of pathological complete responseClinical trialsHER2)-negative breast cancerPhase 3 randomized clinical trialLuminal B tumorsPathological complete responseLuminal A tumorsEarly-stage diseaseRandomized clinical trialsStage II to IIIAnastrozole armNeoadjuvant anastrozoleTumor Ki67Postmenopausal patientsB tumorsComplete responseA tumors
2022
The Phase II MutHER Study of Neratinib Alone and in Combination with Fulvestrant in HER2-Mutated, Non-amplified Metastatic Breast CancerNeratinib and Fulvestrant in HER2-Mutated Breast Cancer
X. C, Luo J, Freedman RA, Pluard TJ, Nangia JR, Lu J, Valdez-Albini F, Cobleigh M, Jones JM, Lin NU, Winer EP, Marcom PK, Thomas S, Anderson J, Haas B, Bucheit L, Bryce R, Lalani AS, Carey LA, Goetz MP, Gao F, Kimmick G, Pegram MD, Ellis MJ, Bose R. The Phase II MutHER Study of Neratinib Alone and in Combination with Fulvestrant in HER2-Mutated, Non-amplified Metastatic Breast CancerNeratinib and Fulvestrant in HER2-Mutated Breast Cancer. Clinical Cancer Research 2022, 28: 1258-1267. PMID: 35046057, DOI: 10.1158/1078-0432.ccr-21-3418.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerER cohortEstrogen receptor-positive breast cancerReceptor-positive breast cancerClinical benefit rateDual HER2 blockadePhase II trialEfficacy of neratinibHER2 blockadeNeratinib monotherapyStable diseaseII trialHER2 mutationsLobular histologyPartial responseEndocrine resistanceBenefit ratePatientsFurther evaluationCancerFulvestrantHER2NeratinibProgression
2020
Acquired FGFR and FGF Alterations Confer Resistance to Estrogen Receptor (ER) Targeted Therapy in ER+ Metastatic Breast Cancer
Mao P, Cohen O, Kowalski KJ, Kusiel JG, Buendia-Buendia JE, Cuoco MS, Exman P, Wander SA, Waks AG, Nayar U, Chung J, Freeman S, Rozenblatt-Rosen O, Miller VA, Piccioni F, Root DE, Regev A, Winer EP, Lin NU, Wagle N. Acquired FGFR and FGF Alterations Confer Resistance to Estrogen Receptor (ER) Targeted Therapy in ER+ Metastatic Breast Cancer. Clinical Cancer Research 2020, 26: 5974-5989. PMID: 32723837, DOI: 10.1158/1078-0432.ccr-19-3958.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBreast NeoplasmsCell Line, TumorDrug Resistance, NeoplasmExome SequencingFemaleFibroblast Growth Factor 3FulvestrantGene Expression Regulation, NeoplasticHumansMCF-7 CellsMiddle AgedMutationNeoplasm MetastasisPiperazinesProtein Kinase InhibitorsPyridinesReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 2Receptors, EstrogenXenograft Model Antitumor AssaysConceptsMetastatic breast cancerEstrogen receptorBreast cancerFGFR pathwaySelective estrogen receptor degraderCDK4/6 inhibitor palbociclibBreast cancer cellsMAPK pathwayWhole-exome sequencingResistant cell linesMAPK pathway inhibitorsFulvestrant resistanceInhibitor palbociclibDrug combinationsFGFR inhibitorsTherapyPathway inhibitorMEK inhibitorsConfer resistanceCancer cellsCancerInsulin receptorGenes/pathwaysBiopsyCell lines
2019
A phase II feasibility study of palbociclib in combination with adjuvant endocrine therapy for hormone receptor-positive invasive breast carcinoma
Mayer EL, DeMichele A, Rugo HS, Miller K, Waks AG, Come SE, Mulvey T, Jeselsohn R, Overmoyer B, Guo H, Barry WT, Bartlett C, Koehler M, Winer EP, Burstein HJ. A phase II feasibility study of palbociclib in combination with adjuvant endocrine therapy for hormone receptor-positive invasive breast carcinoma. Annals Of Oncology 2019, 30: 1514-1520. PMID: 31250880, DOI: 10.1093/annonc/mdz198.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalEstradiolFeasibility StudiesFemaleFulvestrantHumansMiddle AgedNeoplasm InvasivenessNeoplasm StagingPiperazinesProtein Kinase InhibitorsPyridinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneConceptsEarly breast cancerEndocrine therapyAdjuvant palbociclibBreast cancerHormone receptor-positive/HER2-negative metastatic breast cancerHER2-negative metastatic breast cancerPhase II feasibility studyProlong progression-free survivalRandomized phase III trialAdjuvant endocrine therapyPrimary end pointStage III diseasePhase II trialPhase III trialsProgression-free survivalMetastatic breast cancerYears of therapyStart of treatmentInvasive breast carcinomaEligible patientsFebrile neutropeniaPrior chemotherapyWeeks on/1II trialCumulative incidenceEvaluating the addition of bevacizumab to endocrine therapy as first-line treatment for hormone receptor–positive metastatic breast cancer: a pooled analysis from the LEA (GEICAM/2006-11_GBG51) and CALGB 40503 (Alliance) trials
Martín M, Loibl S, Hyslop T, De la Haba-Rodríguez J, Aktas B, Cirrincione CT, Mehta K, Barry WT, Morales S, Carey LA, Garcia-Saenz JA, Partridge A, Martinez-Jañez N, Hahn O, Winer E, Guerrero-Zotano A, Hudis C, Casas M, Rodriguez-Martin C, Furlanetto J, Carrasco E, Dickler MN, Group G, GBG, Oncology A. Evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for hormone receptor–positive metastatic breast cancer: a pooled analysis from the LEA (GEICAM/2006-11_GBG51) and CALGB 40503 (Alliance) trials. European Journal Of Cancer 2019, 117: 91-98. PMID: 31276981, PMCID: PMC6718694, DOI: 10.1016/j.ejca.2019.06.002.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBone NeoplasmsBreast NeoplasmsEvaluation Studies as TopicFemaleFollow-Up StudiesFulvestrantHumansLetrozoleMiddle AgedNeoplasm Recurrence, LocalPrognosisReceptors, EstrogenReceptors, ProgesteroneSoft Tissue NeoplasmsSurvival RateTamoxifenConceptsProgression-free survivalClinical benefit rateObjective response rateEndocrine therapyMetastatic breast cancerOverall survivalGrade IIIBreast cancerHormone receptor-positive metastatic breast cancerMedian progression-free survivalAddition of BevSignificant additional toxicityStandard endocrine therapyDe novo diseaseAddition of bevacizumabFirst-line treatmentPredictors of efficacyNovo diseaseRecurrent diseaseLiver eventsEndocrine sensitivityBenefit rateAdditional toxicityPatientsResponse rate
2018
Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to estrogen receptor–directed therapies
Nayar U, Cohen O, Kapstad C, Cuoco MS, Waks AG, Wander SA, Painter C, Freeman S, Persky NS, Marini L, Helvie K, Oliver N, Rozenblatt-Rosen O, Ma CX, Regev A, Winer EP, Lin NU, Wagle N. Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to estrogen receptor–directed therapies. Nature Genetics 2018, 51: 207-216. PMID: 30531871, DOI: 10.1038/s41588-018-0287-5.Peer-Reviewed Original ResearchConceptsHER2 mutationsEstrogen receptorBreast cancerClinical resistance mechanismsMainstay of treatmentMetastatic breast cancerReceptor-directed therapyCDK6 inhibitor palbociclibPre-existing mutationsMetastatic settingEstrogen independenceInhibitor palbociclibPrimary tumorMetastatic biopsiesInhibitor neratinibTherapyPatientsER mutationsCancerTamoxifenResistance mechanismsDistinct mechanismsMutationsConfer resistanceBiopsy
2017
18F-Fluoroestradiol PET/CT Measurement of Estrogen Receptor Suppression during a Phase I Trial of the Novel Estrogen Receptor-Targeted Therapeutic GDC-0810: Using an Imaging Biomarker to Guide Drug Dosage in Subsequent Trials
Wang Y, Ayres KL, Goldman DA, Dickler MN, Bardia A, Mayer IA, Winer E, Fredrickson J, Arteaga CL, Baselga J, Manning HC, Mahmood U, Ulaner GA. 18F-Fluoroestradiol PET/CT Measurement of Estrogen Receptor Suppression during a Phase I Trial of the Novel Estrogen Receptor-Targeted Therapeutic GDC-0810: Using an Imaging Biomarker to Guide Drug Dosage in Subsequent Trials. Clinical Cancer Research 2017, 23: 3053-3060. PMID: 28011460, PMCID: PMC5474190, DOI: 10.1158/1078-0432.ccr-16-2197.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiomarkers, PharmacologicalBreast NeoplasmsCinnamatesDose-Response Relationship, DrugEstradiolEstrogen Receptor alphaFemaleFulvestrantHumansIndazolesMiddle AgedMolecular ImagingMolecular Targeted TherapyPositron Emission Tomography Computed TomographyReceptors, EstrogenTamoxifenConceptsFES-PET/CTPET/CTClinical trialsER-positive metastatic breast cancerPhase IPhase I clinical trialEstrogen receptor occupancyPhase II trialMetastatic breast cancerSubsequent clinical trialsClin Cancer ResER downregulationFulvestrant therapyAntagonist/Escalation trialII trialTarget lesionsBreast cancerER occupancyUseful biomarkerPatientsReceptor occupancyDay 3Uptake valueDrug dosage
2016
TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer
Jeselsohn R, Barry WT, Migliaccio I, Biagioni C, Zhao J, De Tribolet-Hardy J, Guarducci C, Bonechi M, Laing N, Winer EP, Brown M, Di Leo A, Malorni L. TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer. Clinical Cancer Research 2016, 22: 5755-5764. PMID: 27185372, PMCID: PMC5124409, DOI: 10.1158/1078-0432.ccr-16-0148.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalBreast NeoplasmsDisease-Free SurvivalDouble-Blind MethodEpidermal Growth FactorEstradiolFemaleFulvestrantGene Expression ProfilingHepatocyte Nuclear Factor 3-alphaHumansMiddle AgedPostmenopauseReceptors, EstrogenSignal TransductionTranscription Factor AP-2TranscriptomeConceptsProgression-free survivalBreast cancerPredictive biomarkersCONFIRM studyMetastatic estrogen receptor-positive breast cancerEstrogen receptor-positive breast cancerReceptor-positive breast cancerGene signatureBiologic pathwaysAdvanced breast cancerMetastatic breast cancerMultivariate Cox modelPotential new therapeutic targetEstrogen receptor antagonistNew therapeutic targetsNegative predictive valuePrimary tumor samplesNovel gene signatureMetastatic ERPrimary ERReceptor antagonistFulvestrant treatmentDecreased responseCox modelER levelsPictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial
Krop IE, Mayer IA, Ganju V, Dickler M, Johnston S, Morales S, Yardley DA, Melichar B, Forero-Torres A, Lee SC, de Boer R, Petrakova K, Vallentin S, Perez EA, Piccart M, Ellis M, Winer E, Gendreau S, Derynck M, Lackner M, Levy G, Qiu J, He J, Schmid P. Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Oncology 2016, 17: 811-821. PMID: 27155741, PMCID: PMC5524539, DOI: 10.1016/s1470-2045(16)00106-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBreast NeoplasmsDouble-Blind MethodDrug Resistance, NeoplasmEstradiolEstrogen Receptor AntagonistsFemaleFollow-Up StudiesFulvestrantHumansMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPrognosisReceptor, ErbB-2Receptors, EstrogenSalvage TherapySurvival RateConceptsProgression-free survivalSerious adverse eventsTreatment-related serious adverse eventsWorse adverse eventsPlacebo groupAdverse eventsNon-measurable diseaseAromatase inhibitor treatmentPIK3CA mutationsBreast cancerDay 1Grade 3Inhibitor treatmentDay 15Cycle 1Median progression-free survivalHER2-negative breast cancerEndocrine-resistant breast cancerPIK3CA-mutated tumorsPhase 2 studyPhase 2 trialMetastatic breast cancerWeeks of treatmentAromatase inhibitor resistanceF Hoffmann-La Roche
2014
Endocrine Therapy With or Without Inhibition of Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib for Postmenopausal Women With Hormone Receptor–Positive Advanced Breast Cancer—CALGB 40302 (Alliance)
Burstein HJ, Cirrincione CT, Barry WT, Chew HK, Tolaney SM, Lake DE, Ma C, Blackwell KL, Winer EP, Hudis CA. Endocrine Therapy With or Without Inhibition of Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib for Postmenopausal Women With Hormone Receptor–Positive Advanced Breast Cancer—CALGB 40302 (Alliance). Journal Of Clinical Oncology 2014, 32: 3959-3966. PMID: 25348000, PMCID: PMC4251959, DOI: 10.1200/jco.2014.56.7941.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalDouble-Blind MethodEstradiolFemaleFulvestrantHormonesHumansLapatinibMiddle AgedPostmenopauseProportional Hazards ModelsQuinazolinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneTreatment OutcomeConceptsMedian progression-free survivalProgression-free survivalOverall survivalBreast cancerHormone receptor-positive advanced breast cancerHormone receptor-positive metastatic breast cancerAdvanced ER-positive breast cancerHuman epidermal growth factor receptor 2 (HER2) statusLonger median progression-free survivalEpidermal growth factor receptor 2 statusProgesterone receptor-positive tumorsHuman epidermal growth factor receptor 2ER-positive breast cancerEpidermal growth factor receptor 2Advanced breast cancerPhase III trialsGrowth factor receptor 2Metastatic breast cancerReceptor-positive tumorsHER2-positive tumorsAromatase inhibitor treatmentFactor receptor 2Epidermal growth factor receptorDifferential treatment effectsGrowth factor receptor