2024
Phase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor–Positive, Early-Stage Breast Cancer
Chavez-MacGregor M, Miao J, Pusztai L, Goetz M, Rastogi P, Ganz P, Mamounas E, Paik S, Bandos H, Razaq W, O'Dea A, Kaklamani V, Silber A, Flaum L, Andreopoulou E, Wendt A, Carney J, Sharma P, Gralow J, Lew D, Barlow W, Hortobagyi G. Phase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor–Positive, Early-Stage Breast Cancer. Journal Of Clinical Oncology 2024, 42: 3012-3021. PMID: 38833643, DOI: 10.1200/jco.23.02344.Peer-Reviewed Original ResearchInvasive disease-free survivalHormone receptor-positiveEndocrine therapyOverall survivalBreast cancerHazard ratioReceptor-positiveHigh riskSubset analysisHormone receptor-positive metastatic breast cancerRisk groupsHormone receptor-positive BCEarly-stage breast cancerStratified log-rank testProgression-free survivalEfficacy of everolimusDisease-free survivalMetastatic breast cancerPlacebo-controlled trialSecondary end pointsLog-rank testHighest grade 3Treatment completion ratesPhase IIIEverolimus armDevelopment and validation of RSClin N+ tool for hormone receptor-positive (HR+), HER2-negative (HER2-), node-positive breast cancer.
Pusztai L, Hoag J, Albain K, Barlow W, Stemmer S, Meisner A, Hortobagyi G, Shak S, Hayes D, Rae J, Baehner F, Sharma P, Kalinsky K. Development and validation of RSClin N+ tool for hormone receptor-positive (HR+), HER2-negative (HER2-), node-positive breast cancer. Journal Of Clinical Oncology 2024, 42: 508-508. DOI: 10.1200/jco.2024.42.16_suppl.508.Peer-Reviewed Original ResearchChemoendocrine therapyRecurrence scoreClinicopathological factorsBreast cancerPostmenopausal patientsNode-negative breast cancerNode-positive breast cancerHormone receptor-positiveNode-positive diseaseHR+/HER2- breast cancerRisk estimatesHigh-risk patientsEstimating 5-year riskEstimation of recurrence riskLikelihood ratioPremenopausal patientsHER2-negativeReceptor-positiveChemotherapy benefitEndocrine therapyMenopausal statusRisk patientsInvasive diseasePrognostic informationPostmenopausal model
2023
Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy
Licata L, Barreca M, Galbardi B, Dugo M, Viale G, Győrffy B, Karn T, Pusztai L, Gianni L, Callari M, Bianchini G. Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy. British Journal Of Cancer 2023, 129: 2025-2033. PMID: 37935787, PMCID: PMC10703787, DOI: 10.1038/s41416-023-02477-7.Peer-Reviewed Original ResearchConceptsNeoadjuvant chemotherapyPoor prognosisBreast cancerTreatment responseHigher pathological complete response rateResponse rateHigh pathological response ratePathological complete response ratePathological response rateComplete response rateHigher proliferationHigh recurrence riskMolecular featuresEndocrine therapyLower ERHigh TMBDismal outcomePIK3CA mutationsMethodsGene expression dataClinical dataT cellsPotential therapyRecurrence riskTumorsUnique molecular featuresLBA20 A randomized, double-blind trial of nivolumab (NIVO) vs placebo (PBO) with neoadjuvant chemotherapy (NACT) followed by adjuvant endocrine therapy (ET) ± NIVO in patients (pts) with high-risk, ER+ HER2− primary breast cancer (BC)
Loi S, Curigliano G, Salgado R, Diaz R, Delaloge S, Rojas C, Kok M, Manich C, Harbeck N, Mittendorf E, Yardley D, Pusztai L, Zaizar A, Ungureanu A, Ades F, Chandra R, Nathani R, Pacius M, Wu J, McArthur H. LBA20 A randomized, double-blind trial of nivolumab (NIVO) vs placebo (PBO) with neoadjuvant chemotherapy (NACT) followed by adjuvant endocrine therapy (ET) ± NIVO in patients (pts) with high-risk, ER+ HER2− primary breast cancer (BC). Annals Of Oncology 2023, 34: s1259-s1260. DOI: 10.1016/j.annonc.2023.10.010.Peer-Reviewed Original ResearchEffects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226
Rutherford D, Medley S, Henderson N, Gersch C, Vandenberg T, Albain K, Dakhil S, Tirumali N, Gralow J, Hortobagyi G, Pusztai L, Mehta R, Hayes D, Kidwell K, Henry N, Barlow W, Rae J, Hertz D. Effects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226. Pharmacogenomics 2023, 24: 665-673. PMID: 37615099, PMCID: PMC10565537, DOI: 10.2217/pgs-2023-0097.Peer-Reviewed Original ResearchRadiotherapy Use and Incidence of Locoregional Recurrence in Patients With Favorable-Risk, Node-Positive Breast Cancer Enrolled in the SWOG S1007 Trial
Jagsi R, Barlow W, Woodward W, Connolly E, Mahtani R, Shumway D, Speers C, Stecklein S, Zeidan Y, Zhang H, Sharma P, Pusztai L, Hortobagyi G, Kalinsky K. Radiotherapy Use and Incidence of Locoregional Recurrence in Patients With Favorable-Risk, Node-Positive Breast Cancer Enrolled in the SWOG S1007 Trial. JAMA Oncology 2023, 9: 1083-1089. PMID: 37410451, PMCID: PMC10326730, DOI: 10.1001/jamaoncol.2023.1984.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalDisease-free survivalLocoregional recurrenceBreast-conserving surgeryBreast cancerLocoregional therapyCumulative incidenceRecurrence scoreRadiotherapy informationERBB2-negative breast cancerPredictors of LRRRate of LRRSecondary analysisNode-positive breast cancerBreast Recurrence ScoreLimited nodal diseaseLower locoregional recurrenceOmission of chemotherapyAxillary surgeryRadiotherapy receiptEndocrine therapyN1 diseaseNodal diseaseLocoregional treatmentMenopausal statusPersistence to extended adjuvant endocrine therapy following Breast Cancer Index (BCI) testing in women with early-stage hormone receptor-positive (HR +) breast cancer
Foldi J, Tsagianni A, Salganik M, Schnabel C, Brufsky A, van Londen G, Pusztai L, Sanft T. Persistence to extended adjuvant endocrine therapy following Breast Cancer Index (BCI) testing in women with early-stage hormone receptor-positive (HR +) breast cancer. BMC Cancer 2023, 23: 606. PMID: 37391697, PMCID: PMC10314405, DOI: 10.1186/s12885-023-11104-w.Peer-Reviewed Original ResearchConceptsAdjuvant endocrine therapyEarly-stage hormone receptor-positive breast cancerHormone receptor-positive breast cancerReceptor-positive breast cancerEndocrine therapyBreast cancerLate breast cancer recurrenceExtended endocrine therapyNon-persistence ratesIntolerable side effectsBone density scanBreast cancer recurrenceHigher likelihoodRate of persistenceElectronic health recordsConclusionsIn patientsMedication persistenceTreatment persistenceLow patientsMetastatic recurrenceCancer recurrenceCommon reasonSide effectsPatientsStage IComparing the prognostic and predictive utility of serum thymidine kinase 1 and CA 15-3 in patients with hormone receptor positive metastatic breast cancer starting first-line endocrine therapy in SWOG S0226.
Cobain E, Barlow W, Paoletti C, Bergqvist M, Williams A, Ritzen H, Mehta R, Gralow J, Hortobagyi G, Albain K, Pusztai L, Sharma P, Godwin A, Thompson A, Hayes D, Rae J. Comparing the prognostic and predictive utility of serum thymidine kinase 1 and CA 15-3 in patients with hormone receptor positive metastatic breast cancer starting first-line endocrine therapy in SWOG S0226. Journal Of Clinical Oncology 2023, 41: 1076-1076. DOI: 10.1200/jco.2023.41.16_suppl.1076.Peer-Reviewed Original ResearchProgression-free survivalMetastatic breast cancerThymidine kinase 1 activityHormone receptor-positive metastatic breast cancerPositive metastatic breast cancerOverall survivalEndocrine therapyCA 15Breast cancerCA15-3Predictors of PFSFirst-line endocrine therapySubsequent progression-free survivalWorse progression-free survivalSerum thymidine kinase 1Systemic endocrine therapyMultivariable Cox modelCox regression analysisWorse overall survivalHypothesis-generating dataCycles of treatmentTamoxifen useSystemic therapySerum levelsMultivariable analysisThymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226)
Bergqvist M, Nordmark A, Williams A, Paoletti C, Barlow W, Cobain E, Mehta R, Gralow J, Hortobagyi G, Albain K, Pusztai L, Sharma P, Godwin A, Thompson A, Hayes D, Rae J. Thymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226). Biomarkers 2023, 28: 313-322. PMID: 36647745, PMCID: PMC10681159, DOI: 10.1080/1354750x.2023.2168063.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerNegative predictive valueEndocrine therapyThymidine kinase activityLower riskSingle-agent endocrine therapyMetastatic breast cancer patientsLonger progression-free survivalHigh negative predictive valueProgression-free survivalBreast cancer patientsSerum thymidine kinase activityAdditional therapyOverall survivalSuch patientsCancer patientsBlood drawEarly progressionDisease progressionRapid progressionBreast cancerPatientsSubsequent timepointsPredictive valuePotential biomarkersEvaluation of the Sensitivity to Endocrine Therapy Index and 21-Gene Breast Recurrence Score in the SWOG S8814 Trial
Speers C, Symmans W, Barlow W, Trevarton A, The S, Du L, Rae J, Shak S, Baehner R, Sharma P, Pusztai L, Hortobagyi G, Hayes D, Albain K, Godwin A, Thompson A. Evaluation of the Sensitivity to Endocrine Therapy Index and 21-Gene Breast Recurrence Score in the SWOG S8814 Trial. Journal Of Clinical Oncology 2023, 41: 1841-1848. PMID: 36649570, PMCID: PMC10082279, DOI: 10.1200/jco.22.01499.Peer-Reviewed Original ResearchConceptsBreast Recurrence ScoreAnthracycline-based chemotherapyDisease-free survivalRecurrence scoreEndocrine therapyTherapy indexAdjuvant anthracycline-based chemotherapyNode-positive breast cancerAdjuvant endocrine therapyPrimary end pointSubset of patientsPostmenopausal patientsChemotherapy benefitTreatment armsPrognostic indexPrognostic informationBreast cancerPrognostic assessmentPrognostic performancePatientsEnd pointTumor samplesChemotherapyClinical validationProportional hazards assumption
2022
The mutational profile of ER-, PR+, HER2- metastatic breast cancer.
Fischbach N, Huang R, Lustberg M, Pelletier M, Pusztai L, Sivakumar S, Sokol E, Ross J, Levy M. The mutational profile of ER-, PR+, HER2- metastatic breast cancer. Journal Of Clinical Oncology 2022, 40: 1025-1025. DOI: 10.1200/jco.2022.40.16_suppl.1025.Peer-Reviewed Original ResearchTriple-negative breast cancerComprehensive genomic profilingMetastatic breast cancerBreast cancerClinical trialsPathology reportsMutational profileHER2- metastatic breast cancerConsecutive breast cancersAnti-estrogen therapyNegative breast cancerPD-L1 IHCPotential therapeutic implicationsHigh rateEndocrine therapyEstrogen therapyPatient ageFoundation MedicineKRAS alterationsRare subtypeHER2 expressionClinical behaviorReceptor phenotypeBreast carcinomaTreatment strategiesBiomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update
Andre F, Ismaila N, Allison KH, Barlow WE, Collyar DE, Damodaran S, Henry NL, Jhaveri K, Kalinsky K, Kuderer NM, Litvak A, Mayer EL, Pusztai L, Raab R, Wolff AC, Stearns V. Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update. Journal Of Clinical Oncology 2022, 40: 1816-1837. PMID: 35439025, DOI: 10.1200/jco.22.00069.Peer-Reviewed Original ResearchConceptsBreast Cancer IndexEarly-stage breast cancerHER2- breast cancerAdjuvant endocrinePositive nodesBreast cancerEndocrine therapyPostmenopausal patientsPremenopausal patientsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Early-stage estrogen receptorTriple-negative breast cancerAdjuvant therapy decisionsASCO Guideline UpdateExtended endocrine therapyProspective-retrospective studyEvidence of recurrenceGrowth factor receptor 2Recurrence-free survivalGenomic testsNegative breast cancerEvidence-based recommendationsFactor receptor 2Outcomes of interest
2021
A Randomized Trial of Fulvestrant, Everolimus, and Anastrozole for the Front-line Treatment of Patients with Advanced Hormone Receptor–positive Breast Cancer, SWOG S1222SWOG S1222
Moore HCF, Barlow WE, Somlo G, Gralow JR, Schott AF, Hayes DF, Kuhn P, Hicks JB, Welter L, Dy PA, Yeon CH, Conlin AK, Balcueva E, Lew DL, Tripathy D, Pusztai L, Hortobagyi GN. A Randomized Trial of Fulvestrant, Everolimus, and Anastrozole for the Front-line Treatment of Patients with Advanced Hormone Receptor–positive Breast Cancer, SWOG S1222SWOG S1222. Clinical Cancer Research 2021, 28: 611-617. PMID: 34844978, PMCID: PMC9782801, DOI: 10.1158/1078-0432.ccr-21-3131.Peer-Reviewed Original ResearchConceptsProgression-free survivalHER2-negative breast cancerFirst-line treatmentBreast cancerAdvanced hormone receptor-positive breast cancerAdvanced hormone-sensitive breast cancerHER2-negative advanced breast cancerHormone receptor-positive breast cancerHormone-sensitive breast cancerRandomized placebo-controlled trialReceptor-positive breast cancerCombination endocrine therapyMetastatic hormone receptorPlacebo-controlled trialAdvanced breast cancerMainstay of treatmentFront-line treatmentBaseline CTCsEndocrine therapyEndocrine treatmentPostmenopausal womenMetastatic diseaseOverall survivalPrognostic impactSystemic therapyEvaluating Serum Thymidine Kinase 1 in Hormone Receptor Positive Metastatic Breast Cancer Patients Receiving First Line Endocrine Therapy in the SWOG S0226 Trial
Paoletti C, Barlow WE, Cobain EF, Bergqvist M, Mehta RS, Gralow JR, Hortobagyi GN, Albain KS, Pusztai L, Sharma P, Godwin AK, Thompson AM, Hayes DF, Rae JM. Evaluating Serum Thymidine Kinase 1 in Hormone Receptor Positive Metastatic Breast Cancer Patients Receiving First Line Endocrine Therapy in the SWOG S0226 Trial. Clinical Cancer Research 2021, 27: clincanres.1562.2021. PMID: 34521624, PMCID: PMC8595696, DOI: 10.1158/1078-0432.ccr-21-1562.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials as TopicFemaleHumansKaplan-Meier EstimateMiddle AgedPrognosisReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRetrospective StudiesThymidine KinaseTreatment OutcomeConceptsProgression-free survivalMetastatic breast cancerFirst-line endocrine therapyOverall survivalEndocrine therapyHormone receptor-positive metastatic breast cancer patientsHormone receptor-positive metastatic breast cancerPositive metastatic breast cancer patientsSubsequent progression-free survivalMetastatic breast cancer patientsWorse progression-free survivalCombination endocrine therapySerum thymidine kinase 1Trial of anastrozoleThymidine kinase 1 activityBreast cancer patientsLog-rank testLine endocrine therapyDu/LAdjuvant tamoxifenPrognostic effectCox regressionPoor prognosisWorse prognosisKaplan-MeierHow did the COVID crisis affect use of neoadjuvant therapy for patients with breast cancer?
Chagpar A, Lannin D, Mougalian S, Berger E, Gross C, Horowitz N, Sanft T, DiGiovanna M, Golshan M, Pusztai L. How did the COVID crisis affect use of neoadjuvant therapy for patients with breast cancer? Journal Of Clinical Oncology 2021, 39: e18708-e18708. DOI: 10.1200/jco.2021.39.15_suppl.e18708.Peer-Reviewed Original ResearchUse of NTNeoadjuvant therapyEarly pandemic periodBreast cancerNon-metastatic breast cancerPractice settingsEarly pandemicFlatiron Health databaseNeoadjuvant endocrine therapyTechnology-enabled abstractionSame period one yearSimilar clinicopathologic featuresLongitudinal electronic health recordsPeriod one yearElectronic health recordsTNBC subsetEndocrine therapyPatient ageTN patientsClinicopathologic featuresContemporary cohortClinical stageCancer clinicCancer managementHigh riskEndocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis
Schettini F, Giuliano M, Giudici F, Conte B, De Placido P, Venturini S, Rognoni C, Di Leo A, Locci M, Jerusalem G, Del Mastro L, Puglisi F, Conte P, De Laurentiis M, Pusztai L, Rimawi MF, Schiff R, Arpino G, De Placido S, Prat A, Generali D. Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis. Cancers 2021, 13: 1458. PMID: 33810205, PMCID: PMC8004645, DOI: 10.3390/cancers13061458.Peer-Reviewed Original ResearchMetastatic breast cancerSingle-agent endocrine therapyNegative metastatic breast cancerEndocrine therapyTarget therapyBreast cancerHormone receptor positive/HER2Phase II/IIIEndocrine-resistant tumorsPIK3CA-mutant tumorsOverall survival benefitValid therapeutic optionInternational treatment guidelinesRisk of relapseLine endocrine therapySystematic literature searchEffective regimenSurvival benefitTreatment guidelinesTherapeutic optionsComparable efficacyPooled resultsClinical trialsClinical subgroupsSensitive diseaseNeoadjuvant endocrine therapy use in early stage breast cancer during the covid-19 pandemic
Park KU, Gregory M, Bazan J, Lustberg M, Rosenberg S, Blinder V, Sharma P, Pusztai L, Shen C, Partridge A, Thompson A. Neoadjuvant endocrine therapy use in early stage breast cancer during the covid-19 pandemic. Breast Cancer Research And Treatment 2021, 188: 249-258. PMID: 33651271, PMCID: PMC7921279, DOI: 10.1007/s10549-021-06153-3.Peer-Reviewed Original ResearchConceptsAxillary lymph node dissectionNeoadjuvant endocrine therapyMedical oncologistsRadiation oncologistsOmission of ALNDEstrogen positive breast cancer patientsPositive breast cancer patientsEarly-stage breast cancerEndocrine therapy useMetastatic axillary diseaseLymph node dissectionBreast cancer patientsMultidisciplinary tumor boardStage breast cancerClinical trial organizationsPercent of practicesUS medical oncologistsCOVID-19 pandemicPre-pandemic timesRegional COVID-19 casesAxillary diseaseMicrometastatic nodesSurgery 2Endocrine therapyLocoregional managementPatterns of treatment with everolimus exemestane in hormone receptor-positive HER2-negative metastatic breast cancer in the era of targeted therapy
Rozenblit M, Mun S, Soulos P, Adelson K, Pusztai L, Mougalian S. Patterns of treatment with everolimus exemestane in hormone receptor-positive HER2-negative metastatic breast cancer in the era of targeted therapy. Breast Cancer Research 2021, 23: 14. PMID: 33514405, PMCID: PMC7844919, DOI: 10.1186/s13058-021-01394-y.Peer-Reviewed Original ResearchConceptsPrior endocrine therapyEndocrine therapyMetastatic breast cancerEffective treatment optionTreatment optionsBreast cancerMedian treatmentMedian OSEE therapyHormone receptor-positive HER2-negative metastatic breast cancerMultivariable Cox proportional hazards regression analysisHER2-negative metastatic breast cancerPrior treatmentCox proportional hazards regression analysisFirst-line therapy initiationProportional hazards regression analysisPrior treatment optionsLines of therapyProportion of patientsKaplan-Meier methodHazards regression analysisPatterns of treatmentElectronic health record-derived dataClinical trial dataOS benefit
2020
Text Messaging to Increase Compliance with Adjuvant Endocrine Therapy in Breast Cancer
Pusztai L, Taylor R, Mougalian SS. Text Messaging to Increase Compliance with Adjuvant Endocrine Therapy in Breast Cancer. Cancer Cell 2020, 38: 323-325. PMID: 32931742, DOI: 10.1016/j.ccell.2020.08.006.Peer-Reviewed Original ResearchAdherence to extended adjuvant endocrine therapy following Breast Cancer Index (BCI) testing in women with early-stage hormone receptor (HR)-positive breast cancers.
Foldi J, Schnabel C, Salganik M, Pusztai L, Sanft T. Adherence to extended adjuvant endocrine therapy following Breast Cancer Index (BCI) testing in women with early-stage hormone receptor (HR)-positive breast cancers. Journal Of Clinical Oncology 2020, 38: 527-527. DOI: 10.1200/jco.2020.38.15_suppl.527.Peer-Reviewed Original ResearchLate distant recurrenceAdjuvant endocrine therapyEndocrine therapyDistant recurrenceDXA scansBreast cancerHigh riskStage IEarly-stage hormone receptorExtended endocrine therapyIntolerable side effectsOsteopenia/osteoporosisPositive breast cancerRate of adherenceSerious adverse effectsBreast cancer recurrenceMajority of ptsHigher likelihoodElectronic health recordsLocal recurrenceMedian ageLate recurrenceMetastatic recurrenceTumor characteristicsMedication adherence