2024
Barriers to and facilitators of improving physical activity and nutrition behaviors during chemotherapy for breast cancer: a sequential mixed methods study
Puklin L, Irwin M, Sanft T, Ferrucci L, Harrigan M, McGowan C, Cartmel B, Zupa M, Winer E, Deyling M, Ligibel J, Basen-Engquist K, Spiegelman D, Sharifi M. Barriers to and facilitators of improving physical activity and nutrition behaviors during chemotherapy for breast cancer: a sequential mixed methods study. Supportive Care In Cancer 2024, 32: 590. PMID: 39141176, DOI: 10.1007/s00520-024-08789-5.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBreast NeoplasmsExerciseFemaleHealth BehaviorHumansLife StyleMiddle AgedQualitative ResearchSurveys and QuestionnairesConceptsPhysical activityLifestyle interventionSelf-reported PA questionnaireSelf-reported diet qualityBreast cancerHealthy Eating Index-2015Stage I-III breast cancerBenefits of PASequential mixed methods studyI-III breast cancerChemotherapy-related symptomsMixed methods studyThematic content analysisBehavioral goalsSense of controlBody mass indexPA questionnaireSemi-structured interviewsMean body mass indexTranscribed verbatimIntervention armTailored educationDiet qualityNutritional behaviorMental benefits
2022
p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
Ni J, Kabraji S, Xie S, Wang Y, Pan P, He X, Liu Z, Leone JP, Long HW, Brown MA, Winer EP, Dillon DAR, Lin NU, Zhao JJ. p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases. Nature Communications 2022, 13: 1473. PMID: 35304445, PMCID: PMC8933392, DOI: 10.1038/s41467-022-29081-2.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBrain NeoplasmsBreast NeoplasmsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase Inhibitor p16FemaleHumansReceptor, ErbB-2ConceptsPatient-derived xenograftsBrain metastasesMetastatic HER2-positive breast cancerBiomarker-driven clinical trialsBreast cancer brain metastasesHER2-positive breast cancerOrthotopic patient-derived xenograftsMajority of HER2Cancer brain metastasesCDK4/6 inhibitionProtein immunohistochemistryClinical trialsBreast cancerHER2Tumor suppressor p16INK4aPatientsMetastasisBCBMAbemaciclibTucatinibXenograftsImmunohistochemistryCancerCDK4/6Trials
2021
Utility of the 21-Gene Recurrence Score in Node-Positive Breast Cancer.
Laws A, Garrido-Castro A, Poorvu P, Winer E, Mittendorf E, King T. Utility of the 21-Gene Recurrence Score in Node-Positive Breast Cancer. Oncology 2021, 35: 77-84. PMID: 33577165, DOI: 10.46883/onc.2021.3502.0077.Peer-Reviewed Original ResearchConceptsRecurrence scorePositive nodesClinical trialsBreast cancerHER2-negative breast cancerNode-positive breast cancerLarge population-based registryNode-positive populationAdjuvant chemotherapy useChemotherapy-treated patientsClinical practice guidelinesCurrent practice patternsPopulation-based registryMultiple clinical trialsPotential predictive valueADAPT trialAdjuvant chemotherapyChemotherapy useEndocrine therapyPostmenopausal patientsChemotherapy benefitExcellent outcomesPractice patternsPractice guidelinesRetrospective analysis
2020
Road Map to Safe and Well-Designed De-escalation Trials of Systemic Adjuvant Therapy for Solid Tumors.
Piccart MJ, Hilbers FS, Bliss JM, Caballero C, Frank ES, Renault P, Naït Kaoudjt R, Schumacher E, Spears PA, Regan MM, Gelber RD, Davidson NE, Norton L, Winer EP. Road Map to Safe and Well-Designed De-escalation Trials of Systemic Adjuvant Therapy for Solid Tumors. Journal Of Clinical Oncology 2020, 38: 4120-4129. PMID: 33052755, DOI: 10.1200/jco.20.01382.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsChemotherapy, AdjuvantHumansNeoplasmsRandomized Controlled Trials as TopicConceptsDe-escalation trialsNorth American Breast Cancer GroupBreast International GroupTreatment de-escalation trialsSystemic adjuvant therapySystemic adjuvant treatmentBreast cancer groupNoninferiority trial designAdjuvant trialsAdjuvant therapyAdjuvant treatmentCancer groupDifferent cancer typesPatient insightPatient's perspectiveEffective treatmentConsensus articleTrial designSolid tumorsField of cancerEnd pointFinancial toxicityCancer typesTrialsAdverse effectsThe Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer
Wander SA, Cohen O, Gong X, Johnson GN, Buendia-Buendia JE, Lloyd MR, Kim D, Luo F, Mao P, Helvie K, Kowalski KJ, Nayar U, Waks AG, Parsons SH, Martinez R, Litchfield LM, Ye XS, Yu C, Jansen VM, Stille JR, Smith PS, Oakley GJ, Chu QS, Batist G, Hughes ME, Kremer JD, Garraway LA, Winer EP, Tolaney SM, Lin NU, Buchanan SG, Wagle N. The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer. Cancer Discovery 2020, 10: 1174-1193. PMID: 32404308, PMCID: PMC8815415, DOI: 10.1158/2159-8290.cd-19-1390.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBiopsyBreast NeoplasmsCell Cycle ProteinsCell Line, TumorCheckpoint Kinase 1Drug Resistance, NeoplasmExome SequencingFemaleGenomicsHumansProtein Kinase InhibitorsProto-Oncogene Proteins c-aktProto-Oncogene Proteins p21(ras)Receptors, SteroidRetinoblastoma Binding ProteinsUbiquitin-Protein LigasesConceptsCyclin-dependent kinase 4/6 inhibitorsMetastatic breast cancerBreast cancerResistant tumorsHormone receptor-positive metastatic breast cancerHormone receptor-positive breast cancerReceptor-positive breast cancerEstrogen receptor expressionCandidate resistance mechanismsWhole-exome sequencingPrecision-based approachesCDK4/6i resistanceMechanisms of resistanceReceptor expressionTherapeutic strategiesCDK4/6iTherapeutic opportunitiesPatient samplesTumorsIssue featurePatientsCancerAcquired ResistanceCancer cellsAlterationsPhase II Single-Arm Study of Preoperative Letrozole for Estrogen Receptor-Positive Postmenopausal Ductal Carcinoma In Situ: CALGB 40903 (Alliance).
Hwang ES, Hyslop T, Hendrix LH, Duong S, Bedrosian I, Price E, Caudle A, Hieken T, Guenther J, Hudis CA, Winer E, Lyss AP, Dickson-Witmer D, Hoefer R, Ollila DW, Hardman T, Marks J, Chen YY, Krings G, Esserman L, Hylton N. Phase II Single-Arm Study of Preoperative Letrozole for Estrogen Receptor-Positive Postmenopausal Ductal Carcinoma In Situ: CALGB 40903 (Alliance). Journal Of Clinical Oncology 2020, 38: 1284-1292. PMID: 32125937, PMCID: PMC7164489, DOI: 10.1200/jco.19.00510.Peer-Reviewed Original ResearchConceptsER-positive DCISMagnetic resonance imagingPreoperative letrozoleEndocrine therapyDuctal carcinomaInvasive cancerH-scorePhase II single-arm studyExtended endocrine therapyMonths of letrozolePrimary endocrine therapyPrimary nonoperative treatmentPrimary end pointBreast magnetic resonance imagingCooperative group trialsSingle-arm studyER H-scoreShort-term coursePositive DCISNonoperative treatmentPostmenopausal patientsPostmenopausal womenFuture trialsStudy protocolBiomarker changes
2019
Personalized Management of Chemotherapy‐Induced Peripheral Neuropathy Based on a Patient Reported Outcome: CALGB 40502 (Alliance)
Sharma MR, Mehrotra S, Gray E, Wu K, Barry WT, Hudis C, Winer EP, Lyss AP, Toppmeyer DL, Moreno‐Aspitia A, Lad TE, Velasco M, Overmoyer B, Rugo HS, Ratain MJ, Gobburu JV. Personalized Management of Chemotherapy‐Induced Peripheral Neuropathy Based on a Patient Reported Outcome: CALGB 40502 (Alliance). The Journal Of Clinical Pharmacology 2019, 60: 444-452. PMID: 31802506, PMCID: PMC7064382, DOI: 10.1002/jcph.1559.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminsAlgorithmsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsComputer SimulationDrug Administration ScheduleDrug TaperingEpothilonesFemaleHumansModels, BiologicalPaclitaxelPatient Reported Outcome MeasuresPeripheral Nervous System DiseasesPrecision MedicineConceptsDose-adjustment algorithmPatient-reported outcome dataEarly time pointsNeuropathy scoreDose adjustmentNanoparticle albuminIndividual patientsTime pointsOutcome dataChemotherapy-induced peripheral neuropathyRandomized phase III trialFirst-line chemotherapyMetastatic breast cancerPhase III trialsPatient-reported outcomesBreast Cancer Treatment
Waks AG, Winer EP. Breast Cancer Treatment. JAMA 2019, 321: 316-316. PMID: 30667503, DOI: 10.1001/jama.2018.20751.Peer-Reviewed Original ResearchBreast Cancer Treatment
Waks AG, Winer EP. Breast Cancer Treatment. JAMA 2019, 321: 288-300. PMID: 30667505, DOI: 10.1001/jama.2018.19323.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerNonmetastatic breast cancerTriple-negative tumorsBreast cancerSystemic therapyTumor subtypesMetastatic triple-negative breast cancerHormone receptor-positive tumorsBreast cancer-specific survivalHuman epidermal growth factor 2Epidermal growth factor 2Small-molecule inhibitor therapyMajor tumor subtypesCancer-specific survivalMedian overall survivalProgesterone receptor expressionMetastatic breast cancerTime of diagnosisReceptor-positive tumorsBreast cancer treatmentErbB2-positive tumorsPreoperative treatment responseERBB2 gene amplificationDistinct risk profilesPalliating symptoms
2018
Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: ASCO Clinical Practice Guideline Update
Giordano SH, Temin S, Chandarlapaty S, Crews JR, Esteva FJ, Kirshner JJ, Krop IE, Levinson J, Lin NU, Modi S, Patt DA, Perlmutter J, Ramakrishna N, Winer EP, Davidson NE. Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: ASCO Clinical Practice Guideline Update. Journal Of Clinical Oncology 2018, 36: jco.2018.79.269. PMID: 29939838, DOI: 10.1200/jco.2018.79.2697.Peer-Reviewed Original ResearchConceptsAdvanced breast cancerBreast cancerSystemic therapyTrastuzumab emtansineEstrogen receptor-positive/progesterone receptor-positive breast cancerAdvanced human epidermal growth factor receptorASCO Clinical Practice Guideline UpdateHER2-positive advanced breast cancerProgesterone receptor-positive breast cancerClinical congestive heart failureClinical Practice Guideline UpdateEvidence-based guideline recommendationsStandard first-line therapyPositive advanced breast cancerLeft ventricular ejection fractionReceptor-positive breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Human epidermal growth factor receptorThird-line settingSecond-line treatmentFirst-line therapyFirst-line treatmentProgression-free survivalTime of progressionHomologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer
Telli ML, Stover DG, Loi S, Aparicio S, Carey LA, Domchek SM, Newman L, Sledge GW, Winer EP. Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer. Breast Cancer Research And Treatment 2018, 171: 21-31. PMID: 29736741, DOI: 10.1007/s10549-018-4807-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsB7-H1 AntigenBiomarkers, TumorDisease SusceptibilityDNA DamageDNA RepairFemaleGene Expression Regulation, NeoplasticGenes, BRCA1Genes, BRCA2Germ-Line MutationHomologous RecombinationHumansImmunityImmunomodulationMolecular Targeted TherapyProgrammed Cell Death 1 ReceptorTriple Negative Breast NeoplasmsConceptsHost anti-tumor immunityAnti-tumor immunityHomologous recombination deficiencyBreast cancerPurposeTriple-negative breast cancerAnti-tumor immune cellsRecombination deficiencyTriple-negative breast cancerCare systemic therapyImmune-directed therapiesImmune cell subsetsHomologous recombination DNA repair deficiencyBRCA2 mutation carriersBiomarker-driven approachBreast cancer subtypesPARP inhibitor olaparibHR-deficient tumorsDNA repair capacityMetastatic diseaseSystemic therapyImmune infiltratesImproved prognosisCell subsetsImmune cellsWorse outcomesEnzalutamide for the Treatment of Androgen Receptor–Expressing Triple-Negative Breast Cancer
Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O'Shaughnessy J, Gradishar W, Schmid P, Winer E, Kelly C, Nanda R, Gucalp A, Awada A, Garcia-Estevez L, Trudeau ME, Steinberg J, Uppal H, Tudor IC, Peterson A, Cortes J. Enzalutamide for the Treatment of Androgen Receptor–Expressing Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2018, 36: jco.2016.71.349. PMID: 29373071, PMCID: PMC5858523, DOI: 10.1200/jco.2016.71.3495.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerClinical benefit rateAR-positive triple-negative breast cancerProgression-free survivalAndrogen receptorNuclear androgen receptorEvaluable subgroupITT populationBreast cancerEnd pointAdverse eventsAdvanced triple-negative breast cancerMedian progression-free survivalTreatment-related grade 3Safety of enzalutamideHigher adverse eventsMedian overall survivalPhase II studyPrimary end pointSecondary end pointsSubset of patientsII studyOverall survivalPostbaseline assessmentSafety profile
2017
Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials
Group E, Asselain B, Barlow W, Bartlett J, Bergh J, Bergsten-Nordström E, Bliss J, Boccardo F, Boddington C, Bogaerts J, Bonadonna G, Bradley R, Brain E, Braybrooke J, Broet P, Bryant J, Burrett J, Cameron D, Clarke M, Coates A, Coleman R, Coombes R, Correa C, Costantino J, Cuzick J, Danforth D, Davidson N, Davies C, Davies L, Di Leo A, Dodwell D, Dowsett M, Duane F, Evans V, Ewertz M, Fisher B, Forbes J, Ford L, Gazet J, Gelber R, Gettins L, Gianni L, Gnant M, Godwin J, Goldhirsch A, Goodwin P, Gray R, Hayes D, Hill C, Ingle J, Jagsi R, Jakesz R, James S, Janni W, Liu H, Liu Z, Lohrisch C, Loibl S, MacKinnon L, Makris A, Mamounas E, Mannu G, Martín M, Mathoulin S, Mauriac L, McGale P, McHugh T, Morris P, Mukai H, Norton L, Ohashi Y, Olivotto I, Paik S, Pan H, Peto R, Piccart M, Pierce L, Poortmans P, Powles T, Pritchard K, Ragaz J, Raina V, Ravdin P, Read S, Regan M, Robertson J, Rutgers E, Scholl S, Slamon D, Sölkner L, Sparano J, Steinberg S, Sutcliffe R, Swain S, Taylor C, Tutt A, Valagussa P, van de Velde C, van der Hage J, Viale G, von Minckwitz G, Wang Y, Wang Z, Wang X, Whelan T, Wilcken N, Winer E, Wolmark N, Wood W, Zambetti M, Zujewski J. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. The Lancet Oncology 2017, 19: 27-39. PMID: 29242041, PMCID: PMC5757427, DOI: 10.1016/s1470-2045(17)30777-5.Peer-Reviewed Original ResearchConceptsBreast-conserving therapyEarly breast cancerNeoadjuvant chemotherapyAdjuvant chemotherapyIndividual patient dataLocal recurrenceBreast cancerSame chemotherapyDistant recurrenceTumor characteristicsTumor responsePartial clinical responseYear local recurrencePatient dataBreast cancer deathsHigher local recurrenceBreast-conserving surgeryClinical tumor responseUK Medical Research CouncilBreast cancer mortalityLong-term outcomesFrequent local recurrenceLog-rank methodBritish Heart FoundationThird of womenDe-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017
Curigliano G, Burstein HJ, Winer EP, Gnant M, Dubsky P, Loibl S, Colleoni M, Regan MM, Piccart-Gebhart M, Senn H, Thürlimann B, André F, Baselga J, Bergh J, Bonnefoi H, Brucker S, Cardoso F, Carey L, Ciruelos E, Cuzick J, Denkert C, Di Leo A, Ejlertsen B, Francis P, Galimberti V, Garber J, Gulluoglu B, Goodwin P, Harbeck N, Hayes D, Huang C, Huober J, Khaled H, Jassem J, Jiang Z, Karlsson P, Morrow M, Orecchia R, Osborne K, Pagani O, Partridge A, Pritchard K, Ro J, Rutgers E, Sedlmayer F, Semiglazov V, Shao Z, Smith I, Toi M, Tutt A, Viale G, Watanabe T, Whelan T, Xu B. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Annals Of Oncology 2017, 28: 1700-1712. PMID: 28838210, PMCID: PMC6246241, DOI: 10.1093/annonc/mdx308.Peer-Reviewed Original ResearchConceptsLow-risk patientsBreast cancerNeoadjuvant therapyPostmenopausal womenEarly-stage breast cancerER-positive breast cancerAvoidance of chemotherapyDe-escalate therapyAdjuvant endocrine treatmentRegional nodal irradiationHigh-risk patientsEarly breast cancerSentinel node biopsyHigh-risk tumorsPositive breast cancerBreast cancer recurrenceExpert consensus conferenceSubstantial new evidenceNodal irradiationBisphosphonate useEndocrine treatmentNeoadjuvant treatmentOvarian suppressionPremenopausal womenPrimary therapyKinetic-Pharmacodynamic Model of Chemotherapy-Induced Peripheral Neuropathy in Patients with Metastatic Breast Cancer Treated with Paclitaxel, Nab-Paclitaxel, or Ixabepilone: CALGB 40502 (Alliance)
Mehrotra S, Sharma MR, Gray E, Wu K, Barry WT, Hudis C, Winer EP, Lyss AP, Toppmeyer DL, Moreno-Aspitia A, Lad TE, Valasco M, Overmoyer B, Rugo H, Ratain MJ, Gobburu JV. Kinetic-Pharmacodynamic Model of Chemotherapy-Induced Peripheral Neuropathy in Patients with Metastatic Breast Cancer Treated with Paclitaxel, Nab-Paclitaxel, or Ixabepilone: CALGB 40502 (Alliance). The AAPS Journal 2017, 19: 1411-1423. PMID: 28620884, PMCID: PMC5711539, DOI: 10.1208/s12248-017-0101-9.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyProportion of patientsMetastatic breast cancerKinetic-pharmacodynamic modelIndirect response modelNab-paclitaxelDose modificationPeripheral neuropathyBreast cancerDrug effectsRandomized phase III trialLinear drug effectFirst-line chemotherapyPhase III trialsTime pointsDose-limiting toxicityLater time pointsEarly time pointsCALGB 40502Neurotoxicity ScaleIII trialsFunctional assessmentChemotherapeutic agentsPatientsCancer
2016
The Role of Proliferation in Determining Response to Neoadjuvant Chemotherapy in Breast Cancer: A Gene Expression–Based Meta-Analysis
Stover DG, Coloff JL, Barry WT, Brugge JS, Winer EP, Selfors LM. The Role of Proliferation in Determining Response to Neoadjuvant Chemotherapy in Breast Cancer: A Gene Expression–Based Meta-Analysis. Clinical Cancer Research 2016, 22: 6039-6050. PMID: 27330058, PMCID: PMC5161615, DOI: 10.1158/1078-0432.ccr-16-0471.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerNeoadjuvant chemotherapyPathologic complete responseBreast cancerGene expression signaturesComplete responseExpression signaturesPrimary breast cancer biopsiesImmune activation signatureBreast cancer biopsiesRole of proliferationClinicopathologic characteristicsSignature scoreImmune activityCancer biopsiesPAM50 subtypesBreast tumorsProliferation differencesCancerActivation signatureNeoadjuvant chemosensitivityChemosensitivityTumorsDNA damageScores3rd ESO–ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3)
Cardoso F, Costa A, Senkus E, Aapro M, André F, Barrios C, Bergh J, Bhattacharyya G, Biganzoli L, Cardoso M, Carey L, Corneliussen-James D, Curigliano G, Dieras V, Saghir N, Eniu A, Fallowfield L, Fenech D, Francis P, Gelmon K, Gennari A, Harbeck N, Hudis C, Kaufman B, Krop I, Mayer M, Meijer H, Mertz S, Ohno S, Pagani O, Papadopoulos E, Peccatori F, Pernault-Llorca F, Piccart M, Pierga J, Rugo H, Shockney L, Sledge G, Swain S, Thomssen C, Tutt A, Vorobiof D, Xu B, Norton L, Winer E. 3rd ESO–ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3). The Breast 2016, 31: 244-259. PMID: 27927580, DOI: 10.1016/j.breast.2016.10.001.Peer-Reviewed Original ResearchCabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study
Tolaney SM, Nechushtan H, Ron IG, Schöffski P, Awada A, Yasenchak CA, Laird AD, O’Keeffe B, Shapiro GI, Winer EP. Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study. Breast Cancer Research And Treatment 2016, 160: 305-312. PMID: 27714541, PMCID: PMC5065609, DOI: 10.1007/s10549-016-4001-y.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalOverall survivalStable diseaseMBC patientsWeek 12Common grade 3/4 adverse eventsOverall median progression-free survivalGrade 3/4 adverse eventsMedian progression-free survivalSolid Tumors version 1.0Metastatic breast cancer patientsOral tyrosine kinase inhibitorResultsForty-five patientsDisease control rateMedian overall survivalPalmar-plantar erythrodysesthesiaResponse Evaluation CriteriaMetastatic breast carcinomaBreast cancer patientsTyrosine kinase inhibitorsCabozantinib monotherapyDiscontinuation studyPrimary endpointRespiratory failureCombination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases
Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nature Medicine 2016, 22: 723-726. PMID: 27270588, PMCID: PMC4938731, DOI: 10.1038/nm.4120.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAminopyridinesAnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsBreast NeoplasmsCarrier ProteinsCaspase 3Cell Cycle ProteinsDNA RepairDrug Resistance, NeoplasmDrug Therapy, CombinationEukaryotic Initiation FactorsEverolimusFemaleGene Expression ProfilingGenomic InstabilityHumansImmunohistochemistryKi-67 AntigenMagnetic Resonance ImagingMechanistic Target of Rapamycin Complex 1MiceMice, SCIDMolecular Targeted TherapyMorpholinesMultiprotein ComplexesNeoplasm TransplantationPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationReceptor, ErbB-2Remission InductionTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesCancer brain metastasesBrain metastasesHER2-positive breast cancer brain metastasesOrthotopic patient-derived xenograftsPI3KPatient-derived xenograftsDurable remissionsTherapeutic responseMouse modelCombined inhibitionCombination inhibitionMetastasisInhibitionRemissionXenograftsMicePhase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor–Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance)
Dickler MN, Barry WT, Cirrincione CT, Ellis MJ, Moynahan ME, Innocenti F, Hurria A, Rugo HS, Lake DE, Hahn O, Schneider BP, Tripathy D, Carey LA, Winer EP, Hudis CA. Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor–Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance). Journal Of Clinical Oncology 2016, 34: 2602-2609. PMID: 27138575, PMCID: PMC5012690, DOI: 10.1200/jco.2015.66.1595.Peer-Reviewed Original ResearchConceptsProlong progression-free survivalHormone receptor-positive metastatic breast cancerMetastatic breast cancerAddition of bevacizumabMedian PFSMeasurable diseaseOverall survivalGrade 3Breast cancerAnti-vascular endothelial growth factor therapyBevacizumab prolongs progression-free survivalDe novo metastatic breast cancerEndothelial growth factor therapyNovo metastatic breast cancerRole of bevacizumabTrial of letrozoleMedian overall survivalTreatment-related toxicityDisease-free intervalPhase III trialsProgression-free survivalGrowth factor therapyStage breast cancerHazard of progressionLine endocrine therapy