2024
Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial
Rediti M, Venet D, Joaquin Garcia A, Maetens M, Vincent D, Majjaj S, El-Abed S, Di Cosimo S, Ueno T, Izquierdo M, Piccart M, Pusztai L, Loi S, Salgado R, Viale G, Rothé F, Sotiriou C. Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial. Nature Communications 2024, 15: 10402. PMID: 39613746, PMCID: PMC11607438, DOI: 10.1038/s41467-024-54621-3.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorBreast NeoplasmsClinical Trials, Phase III as TopicFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedNeoplasm Recurrence, LocalPrognosisRandomized Controlled Trials as TopicReceptor, ErbB-2TrastuzumabTumor MicroenvironmentConceptsHER2-positive breast cancerMolecular subtypesBreast cancerRate of pathological complete responseSensitive to HER2-targeted therapiesClinical trialsRisk of distant recurrenceBreast cancer molecular subtypesPathological complete responseHER2-targeted therapyCancer molecular subtypesPotential clinical implicationsNeoALTTO trialDistant recurrenceComplete responseAdjuvant trastuzumabPrognostic/predictive valueHeterogeneous biologySurvival outcomesI-SPY2Clinical outcomesMicroenvironment featuresGene expression profilesExternal cohortTumorCompletion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023
Mariani M, Viale G, Galbardi B, Licata L, Bosi C, Dugo M, Notini G, Naldini M, Callari M, Criscitiello C, Pusztai L, Bianchini G. Completion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023. JAMA Network Open 2024, 7: e2423390. PMID: 39028669, PMCID: PMC11259908, DOI: 10.1001/jamanetworkopen.2024.23390.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsClinical Trials as TopicCross-Sectional StudiesFemaleHumansImmunotherapyConceptsCross-sectional studyPhase III trialsIII trialsBreast cancerImmunotherapy trialsLandscape of breast cancerPhase II studyPhase II trialPhase I trialSingle-center studySingle-center trialCancer immunotherapy trialsBreast cancer trialsPatient confidenceMain OutcomesFisher's exact testImmuno-oncology trialsTrial featuresProportion of trialsCompletion ratesAdjuvant settingPhase IIReport outcomesII trialPositive resultsImage‐based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno‐oncology Biomarker Working Group on Breast Cancer
Jahangir C, Page D, Broeckx G, Gonzalez C, Burke C, Murphy C, Reis‐Filho J, Ly A, Harms P, Gupta R, Vieth M, Hida A, Kahila M, Kos Z, van Diest P, Verbandt S, Thagaard J, Khiroya R, Abduljabbar K, Haab G, Acs B, Adams S, Almeida J, Alvarado‐Cabrero I, Azmoudeh‐Ardalan F, Badve S, Baharun N, Bellolio E, Bheemaraju V, Blenman K, Fujimoto L, Burgues O, Chardas A, Cheang M, Ciompi F, Cooper L, Coosemans A, Corredor G, Portela F, Deman F, Demaria S, Dudgeon S, Elghazawy M, Fernandez‐Martín C, Fineberg S, Fox S, Giltnane J, Gnjatic S, Gonzalez‐Ericsson P, Grigoriadis A, Halama N, Hanna M, Harbhajanka A, Hart S, Hartman J, Hewitt S, Horlings H, Husain Z, Irshad S, Janssen E, Kataoka T, Kawaguchi K, Khramtsov A, Kiraz U, Kirtani P, Kodach L, Korski K, Akturk G, Scott E, Kovács A, Lænkholm A, Lang‐Schwarz C, Larsimont D, Lennerz J, Lerousseau M, Li X, Madabhushi A, Maley S, Narasimhamurthy V, Marks D, McDonald E, Mehrotra R, Michiels S, Kharidehal D, 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, Rajpoot N, Rapoport B, Rau T, Ribeiro J, Rimm D, Vincent‐Salomon A, Saltz J, Sayed S, Hytopoulos E, Mahon S, Siziopikou K, Sotiriou C, Stenzinger A, Sughayer M, Sur D, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson E, Tramm T, Tran W, van der Laak J, Verghese G, Viale G, Wahab N, Walter T, Waumans Y, Wen H, Yang W, Yuan Y, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Stovgaard E, Salgado R, Gallagher W, Rahman A. Image‐based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno‐oncology Biomarker Working Group on Breast Cancer. The Journal Of Pathology 2024, 262: 271-288. PMID: 38230434, PMCID: PMC11288342, DOI: 10.1002/path.6238.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsFemaleHumansPhenotypePrognosisTumor MicroenvironmentUnited KingdomConceptsImmune profileInternational Immuno-Oncology Biomarker Working GroupIdentification of clinically relevant biomarkersField of immuno-oncologyBiomarker Working GroupManagement of cancer patientsImmune profiling of tumorsClinical trial perspectiveTranslational implicationsProfiling of tumorsIndividual tumor cellsPredicting disease prognosisClinically relevant biomarkersSubtypes of cancerImmuno-oncologyTumor microenvironmentMultiplex immunohistochemistryTreatment responseTumor cellsBreast cancerTumor samplesCancer patientsTreatment choiceDisease prognosisRelevant biomarkers
2023
Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer
Kyalwazi B, Yau C, Campbell M, Yoshimatsu T, Chien A, Wallace A, Forero-Torres A, Pusztai L, Ellis E, Albain K, Blaes A, Haley B, Boughey J, Elias A, Clark A, Isaacs C, Nanda R, Han H, Yung R, Tripathy D, Edmiston K, Viscusi R, Northfelt D, Khan Q, Asare S, Wilson A, Hirst G, Lu R, Symmans W, Yee D, DeMichele A, van ’t Veer L, Esserman L, Olopade O. Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer. JAMA Network Open 2023, 6: e2349646. PMID: 38153734, PMCID: PMC10755617, DOI: 10.1001/jamanetworkopen.2023.49646.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsDisease-Free SurvivalFemaleHumansRacial GroupsRetrospective StudiesTranscriptomeConceptsDistant recurrence-free survivalPathologic complete responseErbB2-negative tumorsWorse distant recurrence-free survivalEarly breast cancerWhite patientsBreast cancerBlack patientsGene expression signaturesReceptor subtypesStage II/III breast cancerHigh-risk early breast cancerCox proportional hazards regression modelHigh-risk breast cancerClinical trial end pointsProportional hazards regression modelsTumor receptor subtypeRetrospective cohort studyPrimary tumor sizeRecurrence-free survivalTrial end pointsBreast cancer outcomesLong-term outcomesHazards regression modelsExpression signaturesBreast 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 ResearchMeSH KeywordsBiomarkersBreast NeoplasmsCell ProliferationCyclinsDisease-Free SurvivalFemaleHumansNeoadjuvant TherapyPrognosisConceptsNeoadjuvant 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 featuresImmunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials
Rediti M, Fernandez-Martinez A, Venet D, Rothé F, Hoadley K, Parker J, Singh B, Campbell J, Ballman K, Hillman D, Winer E, El-Abed S, Piccart M, Di Cosimo S, Symmans W, Krop I, Salgado R, Loi S, Pusztai L, Perou C, Carey L, Sotiriou C. Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials. Nature Communications 2023, 14: 7053. PMID: 37923752, PMCID: PMC10624889, DOI: 10.1038/s41467-023-42635-2.Peer-Reviewed Original ResearchConceptsEvent-free survivalHER2-positive breast cancerPathological complete responseCALGB 40601Breast cancerBreast pathological complete responseStromal tumor-infiltrating lymphocytesHormone receptor statusPhase III trialsClinical nodal statusIndependent prognostic factorTumor-infiltrating lymphocytesIdentification of patientsBreast cancer prognosisT cell receptorNeoadjuvant paclitaxelNeoadjuvant therapyIII trialsNodal statusComplete responsePrognostic factorsPrognostic scoreReceptor statusClinicopathological featuresResidual diseaseVitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221.
Chen C, Zirpoli G, Barlow W, Budd G, McKiver B, Pusztai L, Hortobagyi G, Albain K, Damaj M, Godwin A, Thompson A, Henry N, Ambrosone C, Stringer K, Hertz D. Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221. Journal Of The National Comprehensive Cancer Network 2023, 21: 1172-1180.e3. PMID: 37935109, PMCID: PMC10976748, DOI: 10.6004/jnccn.2023.7062.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyVitamin D insufficiencyD insufficiencyVitamin DPaclitaxel scheduleMechanical hypersensitivityPeripheral neuropathyRisk factorsDeficient dietPaclitaxel-Induced Peripheral NeuropathyEarly-stage breast cancerPaclitaxel-containing chemotherapyVitamin D supplementationSufficient vitamin DVitamin D deficiencyBody mass indexMultiple logistic regressionSelf-reported raceD supplementationD deficiencySensitized miceProspective trialFemale patientsMass indexPredictive biomarkersMolecular Characterization of HER2-Low Invasive Breast Carcinoma by Quantitative RT-PCR Using Oncotype DX Assay
Lin H, Can T, Kahn A, Flannery C, Hoag J, Akkunuri A, Bailey H, Baehner R, Pusztai L, Rozenblit M. Molecular Characterization of HER2-Low Invasive Breast Carcinoma by Quantitative RT-PCR Using Oncotype DX Assay. The Oncologist 2023, 28: e973-e976. PMID: 37656608, PMCID: PMC10546821, DOI: 10.1093/oncolo/oyad249.Peer-Reviewed Original ResearchConceptsHER2 mRNA levelsIHC 0MRNA levelsOncotype DX recurrence score resultsEstrogen receptor-positive breast cancerReceptor-positive breast cancerCurrent adjuvant chemotherapyOncotype DX assayRecurrence Score resultsPositive breast cancerInvasive breast carcinomaIHC score 0Adjuvant chemotherapyQuantitative RT-PCRBreast carcinomaPositive statusScore 0Breast cancerStage IYale cohortHigher mRNA levelsCancerRT-PCRPatientsHER2Effects 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 ResearchDe Novo Oligometastatic Breast Cancer
Pusztai L, Rozenblit M, Dubsky P, Bachelot T, Kirby A, Linderholm B, White J, Chmura S, Carey L, Chua B, Miller K. De Novo Oligometastatic Breast Cancer. Journal Of Clinical Oncology 2023, 41: 5237-5241. PMID: 37607325, PMCID: PMC10691789, DOI: 10.1200/jco.23.00911.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 ResearchMeSH KeywordsBreast NeoplasmsFemaleHumansIncidenceMastectomyMastectomy, SegmentalMiddle AgedNeoplasm Recurrence, LocalRadiotherapy, AdjuvantConceptsInvasive 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 statusStandardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP
Litton J, Regan M, Pusztai L, Rugo H, Tolaney S, Garrett-Mayer E, Amiri-Kordestani L, Basho R, Best A, Boileau J, Denkert C, Foster J, Harbeck N, Jacene H, King T, Mason G, O'Sullivan C, Prowell T, Richardson A, Sepulveda K, Smith M, Tjoe J, Turashvili G, Woodward W, Butler L, Schwartz E, Korde L. Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP. Journal Of Clinical Oncology 2023, 41: 4433-4442. PMID: 37433103, PMCID: PMC10522109, DOI: 10.1200/jco.23.00435.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsFemaleHumansNeoadjuvant TherapyProgression-Free SurvivalResearch DesignConceptsSecondary end pointsPathologic complete responseClinical trialsEnd pointStandardized definitionsHormone receptor-positive diseaseCurative-intent surgeryNeoadjuvant clinical trialsPathologic nodal evaluationResidual invasive cancerEfficacy end pointReceptor-positive diseaseBreast cancer clinical trialsResidual cancer burdenAlternative end pointsTrial end pointsRegional lymph nodesCancer end pointsCross-trial comparisonsSurvival end pointsEnd point definitionsCancer clinical trialsDrug Administration (FDA) regulatory considerationsEfficacy outcomesComplete responseASO 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 ResearchPersistence 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 ResearchMeSH KeywordsAdjuvants, ImmunologicBrain-Computer InterfacesBreast NeoplasmsCombined Modality TherapyFemaleHumansRecurrenceConceptsAdjuvant 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 ISystemic Staging of Locally Advanced Breast Cancer: How Hard to Look?
Pusztai L. Systemic Staging of Locally Advanced Breast Cancer: How Hard to Look? Journal Of Clinical Oncology 2023, 41: 3891-3894. PMID: 37348030, DOI: 10.1200/jco.23.00977.Peer-Reviewed Original ResearchThymidine 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 biomarkersAssessment of stained direct cytology smears of breast cancer for whole transcriptome and targeted messenger RNA sequencing
Marczyk M, Fu C, Lau R, Du L, Trevarton A, Sinn B, Gould R, Pusztai L, Hatzis C, Symmans W. Assessment of stained direct cytology smears of breast cancer for whole transcriptome and targeted messenger RNA sequencing. Cancer Cytopathology 2023, 131: 289-299. PMID: 36650408, PMCID: PMC10614161, DOI: 10.1002/cncy.22679.Peer-Reviewed Original ResearchConceptsCytology smearsBreast cancerConcordance correlation coefficientTumor tissue samplesParaffin-embedded sectionsClinical diagnostic proceduresSurgical resectionRNA sequencingTumor stromaCytologic specimensDiagnostic proceduresLin's concordance correlation coefficientPapanicolaou stainCancerTissue samplesDNA mutation testingSmearsSimilar concordanceTranscriptome RNA-SeqDiagnostic cytologyAllele fractionExpression levelsRNA-seqExpression of genesGene expression levelsEvaluation 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 assumptionTumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer
Nanou A, Miao J, Coumans F, Dolce E, Darga E, Barlow W, Smerage J, Paoletti C, Godwin A, Pusztai L, Sharma P, Thompson A, Hortobagyi G, Terstappen L, Hayes D. Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer. JCO Precision Oncology 2023, 7: e2200372. PMID: 36634296, PMCID: PMC9928629, DOI: 10.1200/po.22.00372.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsClinical Trials as TopicFemaleHumansNeoplastic Cells, CirculatingPrognosisProspective StudiesConceptsCycles of chemotherapyMetastatic breast cancerTumor-derived extracellular vesiclesOverall survivalBreast cancerTumor cellsExtracellular vesiclesComplementary prognostic factorComplementary prognostic valuePoor overall survivalAdditional prognostic biomarkerLonger OSPrognostic factorsPrognostic significanceCTC countPrognostic valuePrognostic biomarkerChemotherapyCancerPatientsCTCsCellsBiomarkersImpact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer.
Lambertini M, Ceppi M, Anderson R, Cameron D, Bruzzone M, Franzoi M, Massarotti C, El-Abed S, Wang Y, Lecocq C, Nuciforo P, Rolyance R, Pusztai L, Sohn J, Latocca M, Arecco L, Pistilli B, Ruddy K, Ballestrero A, Del Mastro L, Peccatori F, Partridge A, Saura C, Untch M, Piccart M, Di Cosimo S, de Azambuja E, Demeestere I. Impact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer. Journal Of The National Comprehensive Cancer Network 2023, 21: 33-41.e16. PMID: 36634607, DOI: 10.6004/jnccn.2022.7065.Peer-Reviewed Original ResearchConceptsAnti-HER2 therapyAMH levelsOvarian reserveWeekly paclitaxelAntimüllerian hormoneBreast cancerWeek 2HER2-positive early breast cancerHER2-positive breast cancerSubsequent ovarian functionAnti-HER2 agentsAnti-HER2 treatmentMedian AMH levelsEarly breast cancerTime of surgeryFrozen serum samplesBiomarker analysisNeoALTTO trialPotential gonadotoxicityPremenopausal womenMedian ageAMH valuesOvarian functionAMH declineGonadotoxicity