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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorChumsri, Saranya
dc.contributor.authorLi, Zhuo
dc.contributor.authorSerie, Daniel J.
dc.contributor.authorNorton, Nadine
dc.contributor.authorMashadi-Hossein, Afshin
dc.contributor.authorTenner, Kathleen
dc.contributor.authorSaura Manich, Cristina
dc.date.accessioned2022-09-07T12:08:48Z
dc.date.available2022-09-07T12:08:48Z
dc.date.issued2022-05-24
dc.identifier.citationChumsri S, Li Z, Serie DJ, Norton N, Mashadi-Hossein A, Tenner K, et al. Adaptive immune signature in HER2-positive breast cancer in NCCTG (Alliance) N9831 and NeoALTTO trials. NPJ Breast Cancer. 2022 May 24;8:68.
dc.identifier.issn1662-453X
dc.identifier.urihttp://hdl.handle.net/11351/8055
dc.descriptionBreast cancer; Predictive markers
dc.description.abstractTrastuzumab acts in part through the adaptive immune system. Previous studies showed that enrichment of immune-related gene expression was associated with improved outcomes in HER2-positive (HER2+) breast cancer. However, the role of the immune system in response to lapatinib is not fully understood. Gene expression analysis was performed in 1,268 samples from the North Central Cancer Treatment Group (NCCTG) N9831 and 244 samples from the NeoALTTO trial. In N9831, enrichment of CD45 and immune-subset signatures were significantly associated with improved outcomes. We identified a novel 17-gene adaptive immune signature (AIS), which was found to be significantly associated with improved RFS among patients who received adjuvant trastuzumab (HR 0.66, 95% CI 0.49–0.90, Cox regression model p = 0.01) but not in patients who received chemotherapy alone (HR 0.96, 95% CI 0.67–1.40, Cox regression model p = 0.97). This result was validated in NeoALTTO. Overall, AIS-low patients had a significantly lower pathologic complete response (pCR) rate compared with AIS-high patients (χ2 p < 0.0001). Among patients who received trastuzumab alone, pCR was observed in 41.7% of AIS-high patients compared with 9.8% in AIS-low patients (OR of 6.61, 95% CI 2.09–25.59, logistic regression model p = 0.003). More importantly, AIS-low patients had a higher pCR rate with an addition of lapatinib (51.1% vs. 9.8%, OR 9.65, 95% CI 3.24–36.09, logistic regression model p < 0.001). AIS-low patients had poor outcomes, despite receiving adjuvant trastuzumab. However, these patients appear to benefit from an addition of lapatinib. Further studies are needed to validate the significance of this signature to identify patients who are more likely to benefit from dual anti-HER2 therapy. ClinicalTrials.gov Identifiers: NCT00005970 (NCCTG N9831) and NCT00553358 (NeoALTTO).
dc.language.isoeng
dc.publisherNature Research
dc.relation.ispartofseriesNPJ Breast Cancer;8
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectMama - Càncer - Tractament
dc.subjectExpressió gènica
dc.subjectResposta immunitària
dc.subject.meshBreast Neoplasms
dc.subject.mesh/drug therapy
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshDose-Response Relationship, Immunologic
dc.titleAdaptive immune signature in HER2-positive breast cancer in NCCTG (Alliance) N9831 and NeoALTTO trials
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1038/s41523-022-00430-0
dc.subject.decsneoplasias de la mama
dc.subject.decs/farmacoterapia
dc.subject.decsregulación de la expresión génica neoplásica
dc.subject.decsrelación dosis-respuesta inmunológica
dc.relation.publishversionhttps://doi.org/10.1038/s41523-022-00430-0
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Chumsri S] Jacoby Center for Breast Health, Mayo Clinic, Jacksonville, FL, USA. [Li Z, Serie DJ] Department of Health and Human Services, Mayo Clinic, Jacksonville, FL, USA. [Norton N] Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA. [Mashadi-Hossein A] NanoString, Inc., Seattle, WA, USA. [Tenner K] Department of Health and Human Services, Mayo Clinic, Rochester, MN, USA. [Saura C] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. SOLTI Breast Cancer Research Group, Barcelona, Spain
dc.identifier.pmid35610260
dc.identifier.wos000799816800001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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