2024
The Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer
Dugo M, Huang C, Egle D, Bermejo B, Zamagni C, Seitz R, Nielsen T, Thill M, Antón-Torres A, Russo S, Ciruelos E, Schweitzer B, Ross D, Galbardi B, Greil R, Semiglazov V, Gyorffy B, Colleoni M, Kelly C, Mariani G, Del Mastro L, Blasi O, Callari M, Pusztai L, Valagussa P, Viale G, Gianni L, Bianchini G. The Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer. Clinical Cancer Research 2024, 30: of1-of10. PMID: 39308141, PMCID: PMC11528202, DOI: 10.1158/1078-0432.ccr-24-0149.Peer-Reviewed Original ResearchPathologic complete response ratePathological complete responseTriple-negative breast cancerRNA-seqI-SPY2Immuno-oncologyBreast cancerPatients treated with pembrolizumabTumor-infiltrating lymphocyte countsPublicly available microarray dataPretreatment core biopsiesImmune checkpoint therapyRNA-seq dataPer-protocol populationAvailable microarray dataI-SPY2 trialPDL1 protein expressionNeoadjuvant atezolizumabNeoadjuvant immunotherapyPlus chemotherapyCheckpoint therapyComplete responseTriple-negativeCore biopsyRT-qPCR dataOverall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer
Schmid P, Cortes J, Dent R, McArthur H, Pusztai L, Kümmel S, Denkert C, Park Y, Hui R, Harbeck N, Takahashi M, Im S, Untch M, Fasching P, Mouret-Reynier M, Foukakis T, Ferreira M, Cardoso F, Zhou X, Karantza V, Tryfonidis K, Aktan G, O'Shaughnessy J. Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer. New England Journal Of Medicine 2024 PMID: 39282906, DOI: 10.1056/nejmoa2409932.Peer-Reviewed Original ResearchEarly-stage triple-negative breast cancerTriple-negative breast cancerPembrolizumab-chemotherapy groupPlacebo-chemotherapy groupCycles of pembrolizumabPathological complete responseEvent-free survivalOverall survivalBreast cancerAdjuvant pembrolizumabComplete responseSafety profile of pembrolizumabData cutoff dateUntreated stage IIPlatinum-containing chemotherapyMedian follow-upEstimate overall survivalSecondary end pointsEpirubicin-cyclophosphamideNeoadjuvant pembrolizumabNeoadjuvant therapyDoxorubicin-cyclophosphamideNeoadjuvant chemotherapyDefinitive surgeryPembrolizumabPhosphoenolpyruvate carboxykinase-2 (PCK2) is a therapeutic target in triple-negative breast cancer
Gunasekharan V, Lin H, Marczyk M, Rios-Hoyo A, Campos G, Shan N, Ahmed M, Umlauf S, Gareiss P, Raaisa R, Williams R, Cardone R, Siebel S, Kibbey R, Surovtseva Y, Pusztai L. Phosphoenolpyruvate carboxykinase-2 (PCK2) is a therapeutic target in triple-negative breast cancer. Breast Cancer Research And Treatment 2024, 208: 657-671. PMID: 39177932, DOI: 10.1007/s10549-024-07462-z.Peer-Reviewed Original ResearchMetabolic fluxTriple-negative breast cancerReduced metabolic fluxMDA-MB-231 cellsCell growth in vitroEnzyme assays in vitroMDA-MB-231Potential small molecule inhibitorsPyruvate carboxylaseGrowth in vitroSmall molecule inhibitorsIn silico screeningEnzyme assaysAssay in vitroEnzymatic assayCell lines in vitroEnzyme activityGrowth inhibitory activityBT-549Breast cancerIn vitro screeningBreast cell lines in vitroPhosphoenolpyruvateSignificant growth inhibitory activityLines in vitroAcademic Uphill Battle to Personalize Treatment for Patients With Stage II/III Triple-Negative Breast Cancer
Kok M, Gielen R, Adams S, Lennerz J, Sharma P, Loibl S, Reardon E, Sonke G, Linn S, Delaloge S, Lacombe D, Robinson T, Badve S, Martin M, Balko J, Ignatiadis M, Curigliano G, Wolff A, Mittendorf E, Loi S, Pusztai L, Tolaney S, Salgado R. Academic Uphill Battle to Personalize Treatment for Patients With Stage II/III Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2024, 42: 3523-3529. PMID: 39038259, DOI: 10.1200/jco.24.00372.Peer-Reviewed Original ResearchPeripheral blood immune parameters, response, and adverse events after neoadjuvant chemotherapy plus durvalumab in early-stage triple-negative breast cancer
Foldi J, Blenman K, Marczyk M, Gunasekharan V, Polanska A, Gee R, Davis M, Kahn A, Silber A, Pusztai L. Peripheral blood immune parameters, response, and adverse events after neoadjuvant chemotherapy plus durvalumab in early-stage triple-negative breast cancer. Breast Cancer Research And Treatment 2024, 208: 369-377. PMID: 39002068, DOI: 10.1007/s10549-024-07426-3.Peer-Reviewed Original ResearchImmune-related adverse eventsTriple-negative breast cancerAssociated with pathological responsePathological complete responseNeoadjuvant chemotherapyCytokine levelsPathological responseAdverse eventsBreast cancerEarly-stage triple-negative breast cancerPatients treated with immune checkpoint inhibitorsB cell clonal expansionMeasured serum cytokine levelsImmune checkpoint inhibitorsGM-CSF levelsPeripheral blood cytokine levelsBlood cytokine levelsSerum cytokine levelsB cell receptorMagnetic bead panelBenjamini-Hochberg correctionSample of patientsImmunoSEQ platformCheckpoint inhibitorsComplete responseNeoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study
Dent R, Cortés J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park Y, Hui R, Harbeck N, Takahashi M, Untch M, Fasching P, Cardoso F, Haiderali A, Jia L, Nguyen A, Pan W, O'Shaughnessy J, Schmid P. Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study. Journal Of The National Cancer Institute 2024, 116: 1654-1663. PMID: 38913881, PMCID: PMC11461162, DOI: 10.1093/jnci/djae129.Peer-Reviewed Original ResearchEarly-stage triple-negative breast cancerTriple-negative breast cancerLS mean changeBaseline to weekPatient-reported outcomesAdjuvant pembrolizumabBetween-group differencesKEYNOTE-522Neoadjuvant phaseAdjuvant phaseBreast cancerMean changePathological complete responseEvent-free survivalQuality-of-life resultsNeoadjuvant pembrolizumabPatient-reported outcome assessmentsComplete responseNeoadjuvant chemotherapyEORTC QLQ-30PembrolizumabQuality-of-lifeSecondary objectivesQLQ-30PlaceboIncidence and time to onset of immunotherapy-related adrenal insufficiency in the I-SPY2 trial.
Nanda R, Cohen R, Quandt Z, Basu A, Yau C, Chien A, Pusztai L, Han H, Stringer-Reasor E, Isaacs C, Hershman D, Shatsky R, Perlmutter J, Yee D, DeMichele A, van 't Veer L, Hylton N, Esserman L, Rugo H. Incidence and time to onset of immunotherapy-related adrenal insufficiency in the I-SPY2 trial. Journal Of Clinical Oncology 2024, 42: 584-584. DOI: 10.1200/jco.2024.42.16_suppl.584.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune checkpoint inhibitorsEarly breast cancerIncidence of AIAdrenal insufficiencyI-SPY2Advanced diseaseBreast cancerRisk of immune-related adverse eventsHigh-risk early breast cancerImmune checkpoint inhibitor doseTriple-negative breast cancerAnti-LAG-3Approval of pembrolizumabEvaluate novel agentsICI-based therapyWeekly x 4Rate of adrenal insufficiencyPhase 2 trialI-SPY2 trialTime to onsetAge of ptsCheckpoint inhibitorsNeoadjuvant settingWeekly paclitaxelNavigating practical challenges in immunotherapy for metastatic triple negative breast cancer
Licata L, Dieci M, De Angelis C, Marchiò C, Miglietta F, Cortesi L, Fabi A, Schmid P, Cortes J, Pusztai L, Bianchini G, Curigliano G. Navigating practical challenges in immunotherapy for metastatic triple negative breast cancer. Cancer Treatment Reviews 2024, 128: 102762. PMID: 38776613, DOI: 10.1016/j.ctrv.2024.102762.Peer-Reviewed Original ResearchTriple-negative breast cancerBreast cancerMetastatic triple negative breast cancerManagement of breast cancer patientsTriple negative breast cancerApproval of immunotherapyImmune checkpoint inhibitorsNegative breast cancerBreast cancer patientsEveryday clinical practiceCheckpoint inhibitorsTumor typesCancer patientsClinical trialsCancer therapyImmunotherapyCancerClinical practicePositive resultsCliniciansTumorTherapyPatientsTrialsInhibitorsEvent-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522☆
Pusztai L, Denkert C, O’Shaughnessy J, Cortes J, Dent R, McArthur H, Kümmel S, Bergh J, Park Y, Hui R, Harbeck N, Takahashi M, Untch M, Fasching P, Cardoso F, Zhu Y, Pan W, Tryfonidis K, Schmid P. Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522☆. Annals Of Oncology 2024, 35: 429-436. PMID: 38369015, DOI: 10.1016/j.annonc.2024.02.002.Peer-Reviewed Original ResearchTriple-negative breast cancerEvent-free survivalPathological complete responseResidual cancer burdenEarly-stage triple-negative breast cancerEvent-free survival eventsPembrolizumab groupRCB-2KEYNOTE-522Neoadjuvant pembrolizumabRCB-0Central nervous system recurrenceCancer burdenCycles of paclitaxelIncreased pCR ratePembrolizumab to chemotherapyCycles of doxorubicinCox regression modelsRCB-1Adjuvant pembrolizumabDistant recurrencePCR rateResidual diseaseSystemic recurrenceComplete responseTROPION-Breast03: a randomized phase III global trial of datopotamab deruxtecan ± durvalumab in patients with triple-negative breast cancer and residual invasive disease at surgical resection after neoadjuvant therapy
Bardia A, Pusztai L, Albain K, Ciruelos E, Im S, Hershman D, Kalinsky K, Isaacs C, Loirat D, Testa L, Tokunaga E, Wu J, Dry H, Barlow W, Kozarski R, Maxwell M, Harbeck N, Sharma P. TROPION-Breast03: a randomized phase III global trial of datopotamab deruxtecan ± durvalumab in patients with triple-negative breast cancer and residual invasive disease at surgical resection after neoadjuvant therapy. Therapeutic Advances In Medical Oncology 2024, 16: 17588359241248336. PMID: 38686016, PMCID: PMC11057345, DOI: 10.1177/17588359241248336.Peer-Reviewed Original ResearchInvasive disease-free survivalResidual invasive diseasePathological complete responseTriple-negative breast cancerDisease-free survivalNeoadjuvant therapyInvasive diseaseSurgical resectionBreast cancerHigh risk of disease recurrenceTopoisomerase I inhibitor payloadRisk of disease recurrenceStandard-of-care therapyAdjuvant treatment approachesPhase III studyTreatment of patientsWritten informed consentAntibody-drug conjugatesAged 18-yearsComplete responseNeoadjuvant treatmentInstitutional review boardOverall survivalDisease recurrenceIII studies
2023
Core Needle Biopsies as an Alternative Source for Ex Vivo Expanded TIL for Adoptive Cell Therapy in Triple-Negative Breast Cancer
Coman M, Pusztai L, Hooley R, Andreveja L, Kim L, Joshi N, Bersenev A, Krause D, Park T. Core Needle Biopsies as an Alternative Source for Ex Vivo Expanded TIL for Adoptive Cell Therapy in Triple-Negative Breast Cancer. Journal Of Immunotherapy 2023, 47: 49-53. PMID: 37991241, DOI: 10.1097/cji.0000000000000495.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesCore needle biopsyTriple-negative breast cancerNeedle biopsyBreast cancerEx vivoT-cell receptor clonalityUltrasound-guided core needle biopsyTriple negative breast cancer tumorsMorbidity of surgeryAdoptive cell therapyBreast cancer tumorsTIL generationAdoptive transferTIL culturesMultiple lesionsCytokine secretionMetastatic cancerSame patientTumor tissueCell therapyPatientsCancer tumorsCancerSurgeryPembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer
Takahashi M, Cortés J, Dent R, Pusztai L, McArthur H, Kümmel S, Denkert C, Park Y, Im S, Ahn J, Mukai H, Huang C, Chen S, Kim M, Jia L, Li X, Tryfonidis K, Karantza V, Iwata H, Schmid P. Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer. JAMA Network Open 2023, 6: e2342107. PMID: 37966841, PMCID: PMC10652156, DOI: 10.1001/jamanetworkopen.2023.42107.Peer-Reviewed Original ResearchConceptsEarly triple-negative breast cancerTriple-negative breast cancerEvent-free survivalPathologic complete responseChemotherapy groupNeoadjuvant chemotherapyBreast cancerNeoadjuvant pembrolizumabDefinitive surgeryComplete responseMAIN OUTCOMEEastern Cooperative Oncology Group performance statusCell death ligand 1 (PD-L1) statusDeath ligand 1 (PD-L1) statusTreatment-related adverse eventsNonmetastatic triple-negative breast cancerCycles of pembrolizumabPembrolizumab Plus ChemotherapyTumor PD-L1Unacceptable toxic effectsPD-L1 statusOverall survival analysisAdjuvant pembrolizumabEFS eventsEFS ratesLBA3 Phase III study of neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for early-stage triple-negative breast cancer (TNBC): KEYNOTE-522 Korean subgroup analysis
Park Y, Im S, Ahn J, Kim M, Cortés J, Dent R, Pusztai L, McArthur H, Kummel S, Denkert C, O'Shaughnessy J, Mouret-Reynier M, Ferreira M, Cortes M, Boileau J, Hui R, Zhu Y, Pan W, Karantza V, Schmid P. LBA3 Phase III study of neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for early-stage triple-negative breast cancer (TNBC): KEYNOTE-522 Korean subgroup analysis. Annals Of Oncology 2023, 34: s1467-s1468. DOI: 10.1016/j.annonc.2023.10.132.Peer-Reviewed Original ResearchDual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency
Stecklein S, Barlow W, Pusztai L, Timms K, Kennedy R, Logan G, Seitz R, Badve S, Gökmen-Polar Y, Porter P, Linden H, Tripathy D, Hortobagyi G, Godwin A, Thompson A, Hayes D, Sharma P. Dual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency. JCO Precision Oncology 2023, 7: e2300197. PMID: 37972336, PMCID: PMC10681491, DOI: 10.1200/po.23.00197.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerHomologous recombination deficiencyBreast cancerAdjuvant anthracycline-based chemotherapyTherapeutic vulnerabilitiesRecombination deficiencyDistinct therapeutic vulnerabilitiesAnthracycline-based chemotherapyImmune response signaturesDNA-damaging therapiesFavorable prognosisIntermediate prognosisWorse prognosisImmunologic microenvironmentImmune responseChemoresistant tumorsPrognostic classificationHeterogeneous diseasePrognosisHeterogeneous groupDistinct subgroupsTumorsCancerResponse signatureSimultaneous assessmentPitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer
Thagaard J, Broeckx G, Page D, Jahangir C, Verbandt S, Kos Z, Gupta R, Khiroya R, Abduljabbar K, Haab G, Acs B, Akturk G, Almeida J, Alvarado‐Cabrero I, Amgad M, Azmoudeh‐Ardalan F, Badve S, Baharun N, Balslev E, Bellolio E, Bheemaraju V, Blenman K, Fujimoto L, Bouchmaa N, Burgues O, Chardas A, Cheang M, Ciompi F, Cooper L, Coosemans A, Corredor G, Dahl A, Portela F, Deman F, Demaria S, Hansen J, Dudgeon S, Ebstrup T, Elghazawy M, Fernandez‐Martín C, Fox S, Gallagher W, Giltnane J, Gnjatic S, Gonzalez‐Ericsson P, Grigoriadis A, Halama N, Hanna M, Harbhajanka A, Hart S, Hartman J, Hauberg S, Hewitt S, Hida A, Horlings H, Husain Z, Hytopoulos E, Irshad S, Janssen E, Kahila M, Kataoka T, Kawaguchi K, Kharidehal D, Khramtsov A, Kiraz U, Kirtani P, Kodach L, Korski K, Kovács A, Laenkholm A, Lang‐Schwarz C, Larsimont D, Lennerz J, Lerousseau M, Li X, Ly A, Madabhushi A, Maley S, Narasimhamurthy V, Marks D, McDonald E, Mehrotra R, Michiels S, Minhas F, Mittal S, Moore D, Mushtaq S, Nighat H, Papathomas T, Penault‐Llorca F, Perera R, Pinard C, Pinto‐Cardenas J, Pruneri G, Pusztai L, Rahman A, Rajpoot N, Rapoport B, Rau T, Reis‐Filho J, Ribeiro J, Rimm D, Roslind A, Vincent‐Salomon A, Salto‐Tellez M, Saltz J, Sayed S, Scott E, Siziopikou K, Sotiriou C, Stenzinger A, Sughayer M, Sur D, Fineberg S, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson E, Tramm T, Tran W, van der Laak J, van Diest P, Verghese G, Viale G, Vieth M, Wahab N, Walter T, Waumans Y, Wen H, Yang W, Yuan Y, Zin R, Adams S, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Salgado R, Stovgaard E. Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer. The Journal Of Pathology 2023, 260: 498-513. PMID: 37608772, PMCID: PMC10518802, DOI: 10.1002/path.6155.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesTriple-negative breast cancerBreast cancerTIL assessmentHER2-positive breast cancerRoutine clinical managementTIL evaluationTumor-immune interactionsClinical managementDiscordant assessmentsClinical significancePrognostic biomarkerTIL quantificationCancerDaily practicePatientsTrialsTissue patternsAssessmentLymphocytesBiomarkersASO Visual Abstract: Neoadjuvant Immunotherapy in Early Triple-Negative Breast Cancers—Catching up with the Rest
Kim L, Coman M, Pusztai L, Park T. ASO Visual Abstract: Neoadjuvant Immunotherapy in Early Triple-Negative Breast Cancers—Catching up with the Rest. Annals Of Surgical Oncology 2023, 30: 6452-6453. DOI: 10.1245/s10434-023-13842-4.Peer-Reviewed Original ResearchConceptsEarly triple-negative breast cancerTriple-negative breast cancerNeoadjuvant immunotherapyBreast cancerImmunotherapyCancerIntratumor spatial heterogeneity in programmed death-ligand 1 (PD-L1) protein expression in early-stage breast cancer
Kahn A, Golestani R, Harigopal M, Pusztai L. Intratumor spatial heterogeneity in programmed death-ligand 1 (PD-L1) protein expression in early-stage breast cancer. Breast Cancer Research And Treatment 2023, 201: 289-298. PMID: 37378695, DOI: 10.1007/s10549-023-06977-1.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPD-L1 expressionBreast cancerPD-L1Metastatic triple-negative breast cancerPD-L1 positive casesEarly-stage breast cancerPD-L1 protein expressionImmune checkpoint inhibitorsPD-L1 positivityPD-L1 statusProtein expressionWhole study populationPrimary breast tumorsNegative breast cancerConcordant negative resultsCheckpoint inhibitorsMultiple biopsiesPositive cancersCohen's kappa coefficientStudy populationE1L3N antibodyDiscordance rateBreast tumorsPositive casesNeoadjuvant Immunotherapy in Early, Triple-Negative Breast Cancers: Catching Up with the Rest
Kim L, Coman M, Pusztai L, Park T. Neoadjuvant Immunotherapy in Early, Triple-Negative Breast Cancers: Catching Up with the Rest. Annals Of Surgical Oncology 2023, 30: 6441-6449. PMID: 37349612, DOI: 10.1245/s10434-023-13714-x.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerTumor mutational burdenBreast cancerAdjuvant therapyPathological complete response rateImmune checkpoint modulationComplete response rateExcellent clinical outcomesCombination immunochemotherapyNeoadjuvant immunotherapyNeoadjuvant settingNeoadjuvant chemotherapyOverall survivalPD-L1Checkpoint modulationClinical outcomesMajor trialsMutational burdenResponse rateCancer typesCancerTherapyBiomarkersOutcomesExciting advancesP018 TROPION-Breast03: Datopotamab deruxtecan (Dato-DXd) ± durvalumab vs investigator’s choice of therapy (ICT) for triple-negative breast cancer (TNBC) with residual disease following neoadjuvant therapy
Bardia A, Pusztai L, Albain K, Kalinsky K, Hershman D, Barlow W, Tokunaga E, Ciruelos E, Loirat D, Isaacs C, Testa L, Dry H, Kozarski R, Maxwell M, Harbeck N, Sharma P. P018 TROPION-Breast03: Datopotamab deruxtecan (Dato-DXd) ± durvalumab vs investigator’s choice of therapy (ICT) for triple-negative breast cancer (TNBC) with residual disease following neoadjuvant therapy. The Breast 2023, 68: s23. DOI: 10.1016/s0960-9776(23)00137-6.Peer-Reviewed Original ResearchTriple-negative breast cancerNeoadjuvant therapyResidual diseaseBreast cancerInvestigator's choiceTherapyDurvalumabCancerDiseaseResponse to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer
Liedtke C, Mazouni C, Hess K, André F, Tordai A, Mejia J, Symmans W, Gonzalez-Angulo A, Hennessy B, Green M, Cristofanilli M, Hortobagyi G, Pusztai L. Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2023, 41: 1809-1815. PMID: 36989609, DOI: 10.1200/jco.22.02572.Peer-Reviewed Original ResearchTriple-negative breast cancerPathologic complete response rateNeoadjuvant chemotherapyResidual diseaseBreast cancerProgesterone receptorEstrogen receptorHuman epidermal growth factor receptor 2 (HER2) expressionSurvival rateEpidermal growth factor receptor 2 expressionProgression-free survival ratesM.D. Anderson Cancer CenterComplete response rateOverall survival rateAnderson Cancer CenterReceptor 2 expressionLong-term survivalBone recurrenceNeoadjuvant therapyPostrecurrence survivalVisceral metastasesWorse OSWorse survivalRelapse rateCancer Center