2024
Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update
Loibl S, Jassem J, Sonnenblick A, Parlier D, Winer E, Bergh J, Gelber R, Restuccia E, Im Y, Huang C, Dalenc F, Calvo I, Procter M, Caballero C, Clark E, Raimbault A, McConnell R, Monturus E, de Azambuja E, Gomez H, Bliss J, Viale G, Bines J, Piccart M, Aebi S, Andersson M, Bergh J, Bines J, Bliss J, Bonnefoi H, Caballero C, Cameron D, Cardoso F, Clark E, de Azambuja E, de Haas S, Dent S, Fein L, Frank E, Gelber R, Gnant M, Gomez Moreno H, Im S, Jackisch C, Janni W, Jassem J, Krop I, Kümmel S, Liu T, Loi S, Loibl S, Masuda N, Nili Gam-Yal E, Nyawira B, Pascual T, Piccart M, Pienkowski T, Procter M, Restuccia E, Rodríguez-Lescure Á, Suter T, Thomssen C, Tjan-Heijnen V, Tomasello G, Torres Ulloa M, Twelves C, Viale G, Walshe J, Wilcken N, Winer E. Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update. Journal Of Clinical Oncology 2024, 42: 3643-3651. PMID: 39259927, DOI: 10.1200/jco.23.02505.Peer-Reviewed Original ResearchInvasive disease-free survivalNode-negative cohortNode-positive cohortOverall survivalBreast cancerAPHINITY trialHuman epidermal growth factor receptor 2-positiveEpidermal growth factor receptor 2-positiveInvasive disease-free survival benefitHER2+) breast cancerHuman epidermal growth factor receptor 2-positive breast cancerInterim overall survival analysisYears of median follow-upIntent-to-treat populationInterim analysisHormone receptor-negativeDisease-free survivalMedian follow-upPrimary end pointOverall survival analysisAdjuvant pertuzumabAdjuvant trastuzumabReceptor-negativePlacebo groupClinical trial updateA Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer
Giordano A, Kumthekar P, Jin Q, Kurt B, Ren S, Li T, Leone J, Mittendorf E, Pereslete A, Sharp L, Davis R, DiLullo M, Tayob N, Mayer E, Winer E, Tolaney S, Lin N. A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer. Clinical Cancer Research 2024, 30: of1-of10. PMID: 39226397, PMCID: PMC11528201, DOI: 10.1158/1078-0432.ccr-24-1161.Peer-Reviewed Original ResearchHER2-positive breast cancer brain metastasesBreast cancer brain metastasesClinical benefit rateCancer brain metastasesCentral nervous systemCNS responseBrain metastasesOverall response rateOverall survivalAny-grade adverse eventsEffective systemic therapy optionsNeuro-Oncology Brain MetastasesHER2-positive breast cancerIntracranial partial responseSystemic therapy optionsPhase II studyPhase II trialCNS ORRRANO-BMDose delaysPartial responseII studyPrimary endpointHigh-doseBenefit rateAnalysis of HER2 expression changes from breast primary to brain metastases and the impact of HER2-low expression on overall survival
Pereslete A, Hughes M, Martin A, Files J, Nguyen K, Buckley L, Patel A, Moore A, Winer E, Dillon D, Li T, Tolaney S, Lin N, Sammons S. Analysis of HER2 expression changes from breast primary to brain metastases and the impact of HER2-low expression on overall survival. Neuro-Oncology 2024, noae163. PMID: 39211994, DOI: 10.1093/neuonc/noae163.Peer-Reviewed Original ResearchHER2-low expressionHER2-lowMetastatic breast cancerHER2-positiveHER2 expressionHER2-0Primary tumorBrain metastasesEstrogen receptorBreast cancerHER2-positive primary tumorsASCO-CAP guidelinesNCI-designated centersMultivariate survival analysisCox proportional hazards modelsAntibody-drug conjugatesProportional hazards modelActive antibody-drug conjugateASCO-CAPHER2 gainHER2 statusInferior survivalOverall survivalIntracranial activityRetrospective analysisNeratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022 ☆
Freedman R, Heiling H, Li T, Trapani D, Tayob N, Smith K, Davis R, Pereslete A, DeMeo M, Cotter C, Chen W, Parsons H, Santa-Maria C, Van Poznak C, Moy B, Brufsky A, Melisko M, O’Sullivan C, Ashai N, Rauf Y, Nangia J, Burns R, Savoie J, Wolff A, Winer E, Rimawi M, Krop I, Lin N. Neratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022 ☆. Annals Of Oncology 2024, 35: 993-1002. PMID: 38977064, DOI: 10.1016/j.annonc.2024.07.245.Peer-Reviewed Original ResearchHER2-positive breast cancer brain metastasesBreast cancer brain metastasesT-DM1Ado-trastuzumab emtansineCentral nervous systemOverall survivalCNS objective response rateEfficacy of neratinibT-DM1 exposureObjective response rateCancer brain metastasesPhase II studyMedian OSRANO-BMBrain MetastasesSlow accrualIntracranial activityII studyPrimary endpointPreclinical dataCohort 4Response assessmentTreatment optionsNeratinibPatientsAssociation of higher baseline stress and pain with clinical outcomes: Secondary analysis from Alliance A011502.
Gandhi S, Ballman K, Holmes M, Visvanathan K, Symington B, Carvan M, Matyka C, Weiss A, Winer E, Razaq W, Carey L, Partridge A, Chen W. Association of higher baseline stress and pain with clinical outcomes: Secondary analysis from Alliance A011502. Journal Of Clinical Oncology 2024, 42: 11016-11016. DOI: 10.1200/jco.2024.42.16_suppl.11016.Peer-Reviewed Original ResearchInvasive disease-free survivalBrief Pain InventoryPerceived Stress ScaleOverall survivalPittsburgh Sleep Quality IndexMultivariate Cox modelClinical outcomesBreast cancerCESD-RClinical trialsAssociated with worse clinical outcomesDouble-blind clinical trialCox modelBrief Pain Inventory scoresHormone receptor statusDisease-free survivalEpidemiologic Studies Depression Scale-RevisedCenter for Epidemiologic Studies Depression Scale-RevisedHigher Perceived Stress ScaleBody mass indexNonmetastatic breast cancerSleep qualityCESD-R scoresPerceived Stress Scale scoresPittsburgh Sleep Quality Index scoreOutcomes with trastuzumab deruxtecan (T-DXd) by HER2 status and line of treatment in a large real-world database of patients with metastatic breast cancer.
Tarantino P, Lee D, Foldi J, Soulos P, Gross C, Grinda T, Winer E, Lin N, Krop I, Tolaney S, Lustberg M, Sammons S. Outcomes with trastuzumab deruxtecan (T-DXd) by HER2 status and line of treatment in a large real-world database of patients with metastatic breast cancer. Journal Of Clinical Oncology 2024, 42: 1077-1077. DOI: 10.1200/jco.2024.42.16_suppl.1077.Peer-Reviewed Original ResearchReal-world progression-free survivalLines of therapyMetastatic breast cancerMedian real-world progression-free survivalT-DXdHER2+Overall survivalHER2-lowHER2- patientsBreast cancerHER2- metastatic breast cancerTreat metastatic breast cancerProgression-free survivalKaplan-Meier methodLines of treatmentDatabase of patientsRetrospective observational studyClinical trial settingHER2 casesIHC 0Trastuzumab deruxtecanHR statusHER2 statusTriple-negativeMedian ageAspirin vs Placebo as Adjuvant Therapy for Breast Cancer
Chen W, Ballman K, Partridge A, Hahn O, Briccetti F, Irvin W, Symington B, Visvanathan K, Pohlmann P, Openshaw T, Weiss A, Winer E, Carey L, Holmes M. Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer. JAMA 2024, 331: 1714-1721. PMID: 38683596, PMCID: PMC11059055, DOI: 10.1001/jama.2024.4840.Peer-Reviewed Original ResearchSurvivors of breast cancerInvasive disease-free survival eventsDisease-free survival eventsNonmetastatic breast cancerBreast cancer recurrenceBreast cancerFollow-upRisk of breast cancer recurrenceHazard ratioInvasive cancer eventOverall survivalPrevent breast cancer recurrenceCancer recurrenceBreast cancer survivalInvasive disease-free survivalRates of grade 3Adjuvant breast cancer treatmentTrial of aspirinSurvival eventsDisease-free survivalMedian follow-upDouble-blind trialDaily aspirin therapyStudies of aspirinBreast cancer treatmentContribution of tumour and immune cells to PD‐L1 expression as a predictive biomarker in metastatic triple‐negative breast cancer: exploratory analysis from KEYNOTE‐119
Cortes J, Winer E, Lipatov O, Im S, Gonçalves A, Muñoz‐Couselo E, Lee K, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Hund S, Kulangara K, Karantza V, Mejia J, Ma J, Jelinic P, Huang L, Pruitt S, Emancipator K. Contribution of tumour and immune cells to PD‐L1 expression as a predictive biomarker in metastatic triple‐negative breast cancer: exploratory analysis from KEYNOTE‐119. The Journal Of Pathology Clinical Research 2024, 10: e12371. PMID: 38627977, PMCID: PMC11021797, DOI: 10.1002/2056-4538.12371.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerPD-L1 expressionTriple-negative breast cancerPD-L1 CPSPD-L1Breast cancerTreated metastatic triple-negative breast cancerIncreased programmed death ligand 1PD-L1 IHC 22C3 pharmDxEfficacy of pembrolizumab monotherapyPD-L1 expression assessmentProgrammed death-1 blockadeExpression of PD-L1Objective response rateProgression-free survivalTumor proportion scoreDeath-ligand 1Contribution of tumorImmune cell densityReceiver operating characteristic curveArea under the receiver operating characteristic curvePredictive of responsePembrolizumab monotherapyOverall survivalUniform scoring system
2023
A randomized phase II study of metronomic cyclophosphamide and methotrexate (CM) with or without bevacizumab in patients with advanced breast cancer
Mayer E, Tayob N, Ren S, Savoie J, Spigel D, Burris H, Ryan P, Harris L, Winer E, Burstein H. A randomized phase II study of metronomic cyclophosphamide and methotrexate (CM) with or without bevacizumab in patients with advanced breast cancer. Breast Cancer Research And Treatment 2023, 204: 123-132. PMID: 38019444, DOI: 10.1007/s10549-023-07167-9.Peer-Reviewed Original ResearchObjective response rateProgression-free survivalAdvanced breast cancerPhase II studyMetastatic breast cancerOverall survivalArm ABreast cancerArm BII studyMetronomic chemotherapyRandomized phase II studyGrade adverse eventsMetronomic oral cyclophosphamideOral metronomic chemotherapyMedian overall survivalStandard-dose chemotherapyFurther clinical evaluationMetronomic cyclophosphamideOral cyclophosphamideArm B.Primary endpointSecondary endpointsAdverse eventsDose chemotherapyImpact of pembrolizumab versus chemotherapy on health-related quality of life in patients with metastatic triple-negative breast cancer: results from the phase 3 randomised KEYNOTE-119 study
Schmid P, Lipatov O, Im S, Goncalves A, Muñoz-Couselo E, Lee K, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Mejia J, Zhou X, Haiderali A, Nguyen A, Cortes J, Winer E. Impact of pembrolizumab versus chemotherapy on health-related quality of life in patients with metastatic triple-negative breast cancer: results from the phase 3 randomised KEYNOTE-119 study. European Journal Of Cancer 2023, 195: 113393. PMID: 37976633, DOI: 10.1016/j.ejca.2023.113393.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerCombined positive scoreMetastatic triple-negative breast cancerPD-L1 combined positive scoreHealth-related qualityBreast cancerQLQ-C30 functional scalesTumor PD-L1 expressionGHS/QoLNausea/vomitingPD-L1 expressionStart of treatmentHRQoL resultsEligible patientsHRQoL analysisOverall survivalSystemic therapyClinical outcomesFunctional scalesPhysician's choicePatientsChemotherapyFirst onsetCountry guidelinesMedian TTDCorrelation of SUV on Early Interim PET with Recurrence-Free Survival and Overall Survival in Primary Operable HER2-Positive Breast Cancer (the TBCRC026 Trial)
Hennessy M, Leal J, Huang C, Solnes L, Denbow R, Abramson V, Carey L, Liu M, Rimawi M, Specht J, Storniolo A, Valero V, Vaklavas C, Winer E, Krop I, Wolff A, Cimino-Mathews A, Wahl R, Stearns V, Connolly R. Correlation of SUV on Early Interim PET with Recurrence-Free Survival and Overall Survival in Primary Operable HER2-Positive Breast Cancer (the TBCRC026 Trial). Journal Of Nuclear Medicine 2023, 64: jnumed.123.265853. PMID: 37652539, DOI: 10.2967/jnumed.123.265853.Peer-Reviewed Original ResearchConceptsF-FDG PET/CTHER2-positive breast cancerRecurrence-free survivalPET/CTPathologic complete responseOverall survivalBreast cancerOperable HER2-positive breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Growth factor receptor 2Kaplan-Meier methodStatistical significanceLean body massFactor receptor 2Imaging-based biomarkersCorrelation of SUVHER2 therapyNeoadjuvant trastuzumabNeoadjuvant therapyAdjuvant therapyComplete responsePhysician's discretionOS outcomesCox regressionTucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases
Lin N, Murthy R, Abramson V, Anders C, Bachelot T, Bedard P, Borges V, Cameron D, Carey L, Chien A, Curigliano G, DiGiovanna M, Gelmon K, Hortobagyi G, Hurvitz S, Krop I, Loi S, Loibl S, Mueller V, Oliveira M, Paplomata E, Pegram M, Slamon D, Zelnak A, Ramos J, Feng W, Winer E. Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases. JAMA Oncology 2023, 9: 197-205. PMID: 36454580, PMCID: PMC9716438, DOI: 10.1001/jamaoncol.2022.5610.Peer-Reviewed Original ResearchConceptsErbB2-positive metastatic breast cancerMetastatic breast cancerPlacebo-combination groupPositive metastatic breast cancerNew brain lesionsBrain metastasesOverall survivalSubgroup analysisBrain lesionsBreast cancerIntracranial progression-free survivalPlacebo-controlled clinical trialIntracranial objective response rateStable brain metastasesMedian overall survivalObjective response rateProgression-free survivalExploratory subgroup analysisGreater clinical benefitCNS-PFSHER2CLIMB trialIntracranial outcomesFirst progressionMedian ageClinical benefit
2022
Survival in male breast cancer over the past 3 decades
Leone J, Freedman R, Leone J, Tolaney S, Vallejo C, Leone B, Winer E, Lin N, Hassett M. Survival in male breast cancer over the past 3 decades. Journal Of The National Cancer Institute 2022, 115: 421-428. PMID: 36583555, PMCID: PMC10086618, DOI: 10.1093/jnci/djac241.Peer-Reviewed Original ResearchConceptsBreast cancer-specific survivalMale breast cancerOverall survivalBreast cancerMultivariable Cox regressionCancer-specific survivalEnd Results registryYear of diagnosisBreast cancer mortalityStage of diseaseLog-rank testCox regressionCancer mortalityKaplan-MeierIndependent associationCox modelSignificant improvementSignificant associationCancerLife expectancyDiagnosisSurvivalSignificant differencesPatientsMenAdjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials
Pagani O, Walley B, Fleming G, Colleoni M, Láng I, Gomez H, Tondini C, Burstein H, Goetz M, Ciruelos E, Stearns V, Bonnefoi H, Martino S, Geyer C, Chini C, Puglisi F, Spazzapan S, Ruhstaller T, Winer E, Ruepp B, Loi S, Coates A, Gelber R, Goldhirsch A, Regan M, Francis P, Group F. Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials. Journal Of Clinical Oncology 2022, 41: 1376-1382. PMID: 36521078, PMCID: PMC10419413, DOI: 10.1200/jco.22.01064.Peer-Reviewed Original ResearchConceptsDistant recurrence-free intervalOvarian function suppressionDisease-free survivalPrimary end pointOverall survivalAdjuvant exemestaneEnd pointBreast cancerReceptor-positive early breast cancerHuman epidermal growth factor receptorClinical trial updateYears of exemestaneOverall survival benefitHigh-risk patientsPremenopausal breast cancerRecurrence-free intervalEarly breast cancerGrade 3 tumorsRisk of recurrenceEpidermal growth factor receptorGrowth factor receptorSOFT trialTreat populationOvarian suppressionPremenopausal womenAdjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT
Francis P, Fleming G, Láng I, Ciruelos E, Bonnefoi H, Bellet M, Bernardo A, Climent M, Martino S, Bermejo B, Burstein H, Davidson N, Geyer C, Walley B, Ingle J, Coleman R, Müller B, Le Du F, Loibl S, Winer E, Ruepp B, Loi S, Colleoni M, Coates A, Gelber R, Goldhirsch A, Regan M, Group F. Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT. Journal Of Clinical Oncology 2022, 41: 1370-1375. PMID: 36493334, PMCID: PMC10419521, DOI: 10.1200/jco.22.01065.Peer-Reviewed Original ResearchConceptsOvarian function suppressionDisease-free survivalAdjuvant endocrine therapyPrimary end pointOverall survivalAdjuvant tamoxifenEndocrine therapyEnd pointBreast cancerHuman epidermal growth factor receptor-2-negative tumoursTamoxifen plus ovarian function suppressionHormone receptor-positive breast cancerReceptor-positive breast cancerClinical trial updateOvarian Function TrialPremenopausal breast cancerHigher baseline riskPrior chemotherapyPremenopausal womenTrial updateClinical trialsBaseline riskMultiple end pointsTamoxifenExemestaneMultidimensional 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 damageEfficacy of neoadjuvant chemotherapy in male breast cancer compared with female breast cancer
Leone JP, Hassett MJ, Leone J, Tolaney SM, Vallejo CT, Leone BA, Winer EP, Lin NU. Efficacy of neoadjuvant chemotherapy in male breast cancer compared with female breast cancer. Cancer 2022, 128: 3796-3803. PMID: 36069365, PMCID: PMC9826058, DOI: 10.1002/cncr.34448.Peer-Reviewed Original ResearchConceptsPathologic complete responseFive-year OSNeoadjuvant chemotherapyMale breast cancerBreast cancerTumor subtypesOverall survivalIndependent associationEfficacy of NACInitiation of NACHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2National Cancer DatabaseGrowth factor receptor 2Multivariable logistic regressionFemale breast cancerFactor receptor 2HR-/HER2Complete responseMedian timeMultivariable analysisKaplan-MeierCancer DatabaseReceptor 2Logistic regression191P Correlation of early change in standardized uptake value (SUV) on positron emission tomography (PET/CT) with recurrence-free survival (RFS) and overall survival (OS) in patients with primary operable HER2-positive breast cancer (TBCRC026)
Hennessy M, Leal J, Huang C, Solnes L, Denbow R, Abramson V, Carey L, Liu M, Rimawi M, Specht J, Storniolo A, Valero V, Vaklavas C, Winer E, Krop I, Wolff A, Cimino-Mathews A, Wahl R, Stearns V, Connolly R. 191P Correlation of early change in standardized uptake value (SUV) on positron emission tomography (PET/CT) with recurrence-free survival (RFS) and overall survival (OS) in patients with primary operable HER2-positive breast cancer (TBCRC026). Annals Of Oncology 2022, 33: s623-s624. DOI: 10.1016/j.annonc.2022.07.226.Peer-Reviewed Original ResearchAiming at a Tailored Cure for ERBB2-Positive Metastatic Breast Cancer
Tarantino P, Curigliano G, Parsons HA, Lin NU, Krop I, Mittendorf EA, Waks A, Winer EP, Tolaney SM. Aiming at a Tailored Cure for ERBB2-Positive Metastatic Breast Cancer. JAMA Oncology 2022, 8: 629-635. PMID: 35024766, DOI: 10.1001/jamaoncol.2021.6597.Peer-Reviewed Original ResearchConceptsErbB2-positive metastatic breast cancerMetastatic breast cancerPopulation of patientsBreast cancerDe novo metastaticErb-b2 receptor tyrosine kinase 2High ERBB2 expressionCurrent treatment algorithmsHigh-dose chemotherapyLong-term respondersFraction of patientsAntitumor immune activationReceptor tyrosine kinase 2Quality of lifeOverall survivalSystemic treatmentTrastuzumab deruxtecanPathologic featuresTreatment algorithmFrontline treatmentImmune activationBiologic treatmentPathologic termsDisease burdenLong-term benefitsOverall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer
Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, Campone M, Petrakova K, Winer EP, Janni W, Conte P, Cameron DA, André F, Arteaga CL, Zarate JP, Chakravartty A, Taran T, Le Gac F, Serra P, O'Shaughnessy J. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. New England Journal Of Medicine 2022, 386: 942-950. PMID: 35263519, DOI: 10.1056/nejmoa2114663.Peer-Reviewed Original ResearchConceptsAdvanced breast cancerSignificant overall survival benefitMedian overall survivalOverall survival benefitProgression-free survivalOverall survivalBreast cancerSurvival benefitHER2-negative advanced breast cancerKey secondary end pointProtocol-specified final analysisLonger progression-free survivalHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Negative advanced breast cancerStratified log-rank testFirst-line ribociclibSecondary end pointsFirst-line therapyNew safety signalsPhase 3 trialGrowth factor receptor 2Kaplan-Meier methodLog-rank testFactor receptor 2