2024
Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for PIK3CA-Mutated, Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced or Metastatic Breast Cancer
Jhaveri K, Accordino M, Bedard P, Cervantes A, Gambardella V, Hamilton E, Italiano A, Kalinsky K, Krop I, Oliveira M, Schmid P, Saura C, Turner N, Varga A, Cheeti S, Hilz S, Hutchinson K, Jin Y, Royer-Joo S, Peters U, Shankar N, Schutzman J, Juric D. Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for PIK3CA-Mutated, Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced or Metastatic Breast Cancer. Journal Of Clinical Oncology 2024, 42: 3947-3956. PMID: 39236276, PMCID: PMC11575912, DOI: 10.1200/jco.24.00110.Peer-Reviewed Original ResearchTreatment-related adverse eventsDrug-drug interactionsPreliminary antitumor activityEndocrine therapyStudy treatmentHuman epidermal growth factor receptor 2-negativeBreast cancerTreatment-related adverse event ratesLack of drug-drug interactionsConfirmed objective response rateLocally advanced/metastatic breast cancerCirculating tumor DNA analysisEffect of study treatmentPK drug-drug interactionsAntitumor activityObjective response ratePhase I/Ib studyHormone receptor-positiveProgression-free survivalAdvanced/metastatic breast cancerTumor DNA analysisBiomarkers of responseMetastatic breast cancerYears of ageReceptor-positiveA Pooled Analysis of Trastuzumab Deruxtecan in Patients With HER2-Positive Metastatic Breast Cancer With Brain Metastases
André F, Cortés J, Curigliano G, Modi S, Li W, Park Y, Chung W, Kim S, Yamashita T, Pedrini J, Im S, Tseng L, Harbeck N, Krop I, Nakatani S, Tecson K, Ashfaque S, Egorov A, Hurvitz S. A Pooled Analysis of Trastuzumab Deruxtecan in Patients With HER2-Positive Metastatic Breast Cancer With Brain Metastases. Annals Of Oncology 2024 PMID: 39241960, DOI: 10.1016/j.annonc.2024.08.2347.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerBlinded independent central reviewMetastatic breast cancerBrain metastasesT-DXdOverall survivalCNS-PFSTrastuzumab deruxtecanBreast cancerCentral nervous system progression-free survivalIntracranial responsePooled analysisIntracranial objective response rateSafety of trastuzumab deruxtecanSystemic progression-free survivalObjective response rateORR of patientsProgression-free survivalDuration of responseFood and Drug Administration criteriaIndependent central reviewUS Food and Drug Administration criteriaCompare treatmentsExploratory pooled analysisBM statusPooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03.
Saura C, Cortés J, Modi S, Kim S, Hamilton E, Hurvitz S, Krop I, Curigliano G, Iwata H, Im S, Herbolsheimer P, Karnoub M, Gambhire D, Egorov A, Andre F. Pooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03. Journal Of Clinical Oncology 2024, 42: 1023-1023. DOI: 10.1200/jco.2024.42.16_suppl.1023.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsHER2+ metastatic breast cancerProgression-free survivalMetastatic breast cancerComplete responsePartial responseT-DXdOverall survivalPooled analysisInterstitial lung disease (ILD)/pneumonitisStable disease (SD)/progressive diseaseProlonged progression-free survivalDuration of responseIndependent central reviewNumerically lower ratesLonger treatment durationMetastatic settingRECIST v1.1Trastuzumab deruxtecanOS outcomesCentral reviewAdverse eventsBreast cancerTreatment durationDrug-relatedOutcomes 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 ageTBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients (pts) with metastatic breast cancer (MBC) with germline (g) mutations in PALB2 or somatic (s) mutations in BRCA1 or BRCA2.
Tung N, Robson M, Nanda R, Li T, Vinayak S, Shah P, Khoury K, Kimmick G, Santa-Maria C, Brufsky A, DeMeo M, Vieira J, Carey L, Wulf G, Domchek S, Krop I, Wolff A, Winer E, Garber J. TBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients (pts) with metastatic breast cancer (MBC) with germline (g) mutations in PALB2 or somatic (s) mutations in BRCA1 or BRCA2. Journal Of Clinical Oncology 2024, 42: 1021-1021. DOI: 10.1200/jco.2024.42.16_suppl.1021.Peer-Reviewed Original ResearchProgression-free survivalDuration of responseMetastatic breast cancerClinical benefit rateTriple-negative breast cancerMedian duration of responseMedian progression-free survivalMutant allele frequencyExpansion cohortHER2-negativeHER2-positiveCohort 2aNon-respondersBreast cancerEarly due to slow enrollmentMetastatic chemotherapy regimensResponse to olaparibPhase 2 studyPhase II trialKaplan-Meier methodPredictors of responseCohort of womenWilcoxon rank sum testRank sum testBRCA1mTrastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial
Fehm T, Cottone F, Dunton K, André F, Krop I, Park Y, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego M, Yerushalmi R, Duhoux F, Takano T, Lu W, Egorov A, Kim S. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. The Lancet Oncology 2024, 25: 614-625. PMID: 38697155, DOI: 10.1016/s1470-2045(24)00128-1.Peer-Reviewed Original ResearchConceptsTreatment of physician's choiceMetastatic breast cancerTreatment of physician's choice groupPatient-reported outcomesPhysician's choice groupTrastuzumab deruxtecan groupTrastuzumab deruxtecanPhase 3 trialHER2-positiveBreast cancerGlobal health statusPhysician's choiceEORTC QLQ-C30 global health statusPatient-reported outcome variablesOpen-labelQLQ-C30 global health statusTrastuzumab emtansineDefinitive deteriorationMedian time to definitive deteriorationHER2-positive metastatic breast cancerEastern Cooperative Oncology Group performance statusTreatment durationBlinded independent central reviewQuality of lifeProgression-free survival186P Exploratory pooled safety analysis of trastuzumab deruxtecan (T-DXd) in patients With HER2+ or HER2-low unresectable and/or metastatic breast cancer (mBC) in DESTINY-Breast trials
Park Y, Jacot W, Hurvitz S, Modi S, Yamashita T, Xu B, Tokunaga E, Wang X, Lee K, Iwata H, Krop I, André F, Harbeck N, Rugo H, Mathias E, Pasteiner W, Karnoub M, Ashfaque S, Cheng Y, Kim S. 186P Exploratory pooled safety analysis of trastuzumab deruxtecan (T-DXd) in patients With HER2+ or HER2-low unresectable and/or metastatic breast cancer (mBC) in DESTINY-Breast trials. ESMO Open 2024, 9: 103208. DOI: 10.1016/j.esmoop.2024.103208.Peer-Reviewed Original Research188P A health-related quality-of-life (HRQoL) analysis from DESTINY-Breast04: Trastuzumab deruxtecan (T-DXd) vs capecitabine (CAP) in patients (Pts) with hormone receptor-positive (HR+), HER2-low metastatic breast cancer (mBC)
Ueno N, Cottone F, Dunton K, Cardoso F, Yamashita T, Losada M, Niikura N, Zagouri F, Sohn J, Gombos A, Im S, Pierga J, Krop I, Hashimoto Y, Kim J, Gori S, Jacot W, Bauer R, Aguilar C, Modi S. 188P A health-related quality-of-life (HRQoL) analysis from DESTINY-Breast04: Trastuzumab deruxtecan (T-DXd) vs capecitabine (CAP) in patients (Pts) with hormone receptor-positive (HR+), HER2-low metastatic breast cancer (mBC). ESMO Open 2024, 9: 103210. DOI: 10.1016/j.esmoop.2024.103210.Peer-Reviewed Original Research182MO Trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2+ metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1): Updated overall survival (OS) results of the randomized phase III DESTINY-breast (DB-)02 study
Kim S, André F, Takano T, Fehm T, Park Y, Lee J, Borges G, Kaplan M, Kaczmarek E, Guarneri V, Yonemori K, Pluard T, Prat A, Paterson F, Oakman C, Nakatani S, Ashfaque S, Lu W, Egorov A, Krop I. 182MO Trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2+ metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1): Updated overall survival (OS) results of the randomized phase III DESTINY-breast (DB-)02 study. ESMO Open 2024, 9: 103204. DOI: 10.1016/j.esmoop.2024.103204.Peer-Reviewed Original ResearchThe HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results
Lewis G, Li G, Guo J, Yu S, Fields C, Lee G, Zhang D, Dragovich P, Pillow T, Wei B, Sadowsky J, Leipold D, Wilson T, Kamath A, Mamounas M, Lee M, Saad O, Choeurng V, Ungewickell A, Monemi S, Crocker L, Kalinsky K, Modi S, Jung K, Hamilton E, LoRusso P, Krop I, Schutten M, Commerford R, Sliwkowski M, Cho E. The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results. Nature Communications 2024, 15: 466. PMID: 38212321, PMCID: PMC10784567, DOI: 10.1038/s41467-023-44533-z.Peer-Reviewed Original ResearchConceptsHER2 antibody-drug conjugatesAntibody-drug conjugatesMetastatic breast cancerPhase 1 trialBreast cancerHER2-positive metastatic breast cancerHER2-positive breast cancerObjective response rateDose-escalation studyDuration of responseModel of HER2Anti-tumor activityMechanism of actionTrastuzumab deruxtecanPulmonary toxicityTrastuzumab emtansinePreclinical characterizationResponse rateHigh dosesVivo efficacySecondary objectiveEarly signsPotent cytotoxic agentCytotoxic agentsCancer
2023
Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01) ☆
Saura C, Modi S, Krop I, Park Y, Kim S, Tamura K, Iwata H, Tsurutani J, Sohn J, Mathias E, Liu Y, Cathcart J, Singh J, Yamashita T. Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01) ☆. Annals Of Oncology 2023, 35: 302-307. PMID: 38092229, PMCID: PMC11322859, DOI: 10.1016/j.annonc.2023.12.001.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerTreatment-emergent adverse eventsMetastatic breast cancerObjective response rateProgression-free survivalDuration of responseIndependent central reviewT-DXdAdverse eventsOverall survivalTrastuzumab deruxtecanCentral reviewBreast cancerDrug-related treatment-emergent adverse eventsInterstitial lung disease/pneumonitisResponse rateMedian progression-free survivalPositive metastatic breast cancerHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Sustained antitumor activityAntitumor activityMedian overall survivalPrimary end pointPS2-4 Phase 1/2 study of HER3-DXd in HER3-expressing metastatic breast cancer: Subgroup analysis by HER2 expression
Iwata H, Krop I, Masuda N, Mukohara T, Takahashi S, Nakayama T, Inoue K, Toyama T, Yamamoto Y, Alvarez R, Takahashi M, Osaki A, Ohwada S, Mostillo J, Tanaka Y, Sternberg D, Sellami D. PS2-4 Phase 1/2 study of HER3-DXd in HER3-expressing metastatic breast cancer: Subgroup analysis by HER2 expression. Annals Of Oncology 2023, 34: s1379. DOI: 10.1016/j.annonc.2023.09.107.Peer-Reviewed Original ResearchPatritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3–Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3–Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial
Krop I, Masuda N, Mukohara T, Takahashi S, Nakayama T, Inoue K, Iwata H, Yamamoto Y, Alvarez R, Toyama T, Takahashi M, Osaki A, Saji S, Sagara Y, O'Shaughnessy J, Ohwada S, Koyama K, Inoue T, Li L, Patel P, Mostillo J, Tanaka Y, Sternberg D, Sellami D, Yonemori K. Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3–Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3–Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial. Journal Of Clinical Oncology 2023, 41: 5550-5560. PMID: 37801674, PMCID: PMC10730028, DOI: 10.1200/jco.23.00882.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsHuman epidermal growth factor receptor 3Epidermal growth factor receptor 3Metastatic breast cancerGrowth factor receptor 3Breast cancerReceptor 3Dose expansionPrevious therapyClinical subtypesCommon treatment-emergent adverse eventsPhase I/II trialHER2-positive breast cancerTriple-negative breast cancerDose-escalation partDose-expansion partManageable safety profileAdvanced breast cancerEpidermal growth factor receptorAntibody-drug conjugatesGrowth factor receptorAdvanced diseaseHematologic toxicityII trialObjective response377O A pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) with brain metastases (BMs) from DESTINY-Breast (DB) -01, -02, and -03
Hurvitz S, Modi S, Li W, Park Y, Chung W, Kim S, Cortés J, Yamashita T, Pedrini J, Im S, Tseng L, Harbeck N, Krop I, Curigliano G, Mathias E, Cathcart J, Cagnazzo A, Ashfaque S, Egorov A, André F. 377O A pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) with brain metastases (BMs) from DESTINY-Breast (DB) -01, -02, and -03. Annals Of Oncology 2023, 34: s335-s336. DOI: 10.1016/j.annonc.2023.09.554.Peer-Reviewed Original ResearchAn age-specific pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03.
Krop I, Wildiers H, Hurvitz S, Cortes J, Im S, Iwata H, Andre F, Saura C, Modi S, Kim S, Egorov A, Mathias E, Cathcart J, Cagnazzo A, Cheng Y, Park Y. An age-specific pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03. Journal Of Clinical Oncology 2023, 41: 1006-1006. DOI: 10.1200/jco.2023.41.16_suppl.1006.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsMetastatic breast cancerT-DXdGrade treatment-emergent adverse eventsHER2-positive metastatic breast cancerInterstitial lung disease/pneumonitisFavorable benefit-risk profileAge-specific efficacyGrade 5 eventsPooled safety analysisBenefit-risk profileYears of ageKey efficacy dataOlder ptsSerious AEsAdverse eventsTrastuzumab deruxtecanAdditional efficacyPooled analysisT-DM1Trastuzumab emtansineEfficacy dataBreast cancerSafety dataSafety outcomes186O Patient-reported outcomes (PROs) from DESTINY-Breast02, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2–positive (HER2+) metastatic breast cancer (mBC)
Fehm T, Cottone F, Dunton K, André F, Krop I, Park Y, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego M, Yerushalmi R, Duhoux F, Takano T, Lu W, Livings C, Egorov A, Kim S. 186O Patient-reported outcomes (PROs) from DESTINY-Breast02, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2–positive (HER2+) metastatic breast cancer (mBC). ESMO Open 2023, 8: 101375. DOI: 10.1016/j.esmoop.2023.101375.Peer-Reviewed Original ResearchMultiple PIK3CA mutation clonality correlates with outcomes in taselisib + fulvestrant-treated ER+/HER2–, PIK3CA-mutated breast cancers
Hutchinson K, Chen J, Savage H, Stout T, Schimmoller F, Cortés J, Dent S, Harbeck N, Jacot W, Krop I, Trabucco S, Sivakumar S, Sokol E, Wilson T. Multiple PIK3CA mutation clonality correlates with outcomes in taselisib + fulvestrant-treated ER+/HER2–, PIK3CA-mutated breast cancers. Genome Medicine 2023, 15: 28. PMID: 37101291, PMCID: PMC10131374, DOI: 10.1186/s13073-023-01181-8.Peer-Reviewed Original ResearchConceptsPI3K pathwayBreast cancerK pathwayP110α inhibitionLonger progression-free survivalReceptor tyrosine kinasesProgression-free survivalMetastatic breast cancerComprehensive genomic profilingPI3K pathway genesFurther clinical investigationP110α inhibitorsHigh response rateSolid tumor typesBreast cancer tumorsP110α catalytic subunitClinical trialsClinical investigationIndependent cohortImportant molecular determinantResponse rateTumor typesPIK3CA geneConclusionsOur studyTumor DNATrastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial
André F, Hee Park Y, Kim S, Takano T, Im S, Borges G, Lima J, Aksoy S, Gavila Gregori J, De Laurentiis M, Bianchini G, Roylance R, Miyoshi Y, Armstrong A, Sinha R, Ruiz Borrego M, Lim E, Ettl J, Yerushalmi R, Zagouri F, Duhoux F, Fehm T, Gambhire D, Cathcart J, Wu C, Chu C, Egorov A, Krop I. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. The Lancet 2023, 401: 1773-1785. PMID: 37086745, DOI: 10.1016/s0140-6736(23)00725-0.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerPhysician's choice groupTreatment-emergent adverse eventsBlinded independent central reviewPhase 3 trialProgression-free survivalTrastuzumab deruxtecanIndependent central reviewBreast cancerPhysician's choiceAdverse eventsCentral reviewTrastuzumab emtansineEastern Cooperative Oncology Group performance statusCommon treatment-emergent adverse eventsHigher treatment-emergent adverse eventsMedian progression-free survivalPositive metastatic breast cancerFavorable benefit-risk profilePalmar-plantar erythrodysaesthesiaInterstitial lung diseaseBenefit-risk profileAntibody-drug conjugatesChoice groupTucatinib 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
Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis
Garcia-Recio S, Hinoue T, Wheeler G, Kelly B, Garrido-Castro A, Pascual T, De Cubas A, Xia Y, Felsheim B, McClure M, Rajkovic A, Karaesmen E, Smith M, Fan C, Ericsson P, Sanders M, Creighton C, Bowen J, Leraas K, Burns R, Coppens S, Wheless A, Rezk S, Garrett A, Parker J, Foy K, Shen H, Park B, Krop I, Anders C, Gastier-Foster J, Rimawi M, Nanda R, Lin N, Isaacs C, Marcom P, Storniolo A, Couch F, Chandran U, Davis M, Silverstein J, Ropelewski A, Liu M, Hilsenbeck S, Norton L, Richardson A, Symmans W, Wolff A, Davidson N, Carey L, Lee A, Balko J, Hoadley K, Laird P, Mardis E, King T, Perou C. Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis. Nature Cancer 2022, 4: 128-147. PMID: 36585450, PMCID: PMC9886551, DOI: 10.1038/s43018-022-00491-x.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerHER2-targeted therapiesImmune cell infiltratesMetastatic breast tumorsLiver metastasesCell infiltrateLow-pass whole-genome sequencingSubtype changesT cellsEstrogen receptorTumor subtypesEndothelial contentBreast tumorsMetastasisCell-cell adhesion genesReduced expressionGlobal DNA methylationDNA methylation mechanismsFocal deletionsMolecular featuresWhole-genome sequencingCancerSubtypesRNA sequencing