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Digital PCR quantif...
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Meng, PeiLund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Transl onkogenomik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Transl oncogenomics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
(författare)
Digital PCR quantification of ultrahigh ERBB2 copy number identifies poor breast cancer survival after trastuzumab
- Artikel/kapitelEngelska2024
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LIBRIS-ID:oai:lup.lub.lu.se:12d92176-2798-4bcb-b9da-a0b02639a8ff
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https://lup.lub.lu.se/record/12d92176-2798-4bcb-b9da-a0b02639a8ffURI
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https://doi.org/10.1038/s41523-024-00621-xDOI
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Språk:engelska
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Sammanfattning på:engelska
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HER2/ERBB2 evaluation is necessary for treatment decision-making in breast cancer (BC), however current methods have limitations and considerable variability exists. DNA copy number (CN) evaluation by droplet digital PCR (ddPCR) has complementary advantages for HER2/ERBB2 diagnostics. In this study, we developed a single-reaction multiplex ddPCR assay for determination of ERBB2 CN in reference to two control regions, CEP17 and a copy-number-stable region of chr. 2p13.1, validated CN estimations to clinical in situ hybridization (ISH) HER2 status, and investigated the association of ERBB2 CN with clinical outcomes. 909 primary BC tissues were evaluated and the area under the curve for concordance to HER2 status was 0.93 and 0.96 for ERBB2 CN using either CEP17 or 2p13.1 as reference, respectively. The accuracy of ddPCR ERBB2 CN was 93.7% and 94.1% in the training and validation groups, respectively. Positive and negative predictive value for the classic HER2 amplification and non-amplification groups was 97.2% and 94.8%, respectively. An identified biological “ultrahigh” ERBB2 ddPCR CN group had significantly worse survival within patients treated with adjuvant trastuzumab for both recurrence-free survival (hazard ratio, HR: 3.3; 95% CI 1.1–9.6; p = 0.031, multivariable Cox regression) and overall survival (HR: 3.6; 95% CI 1.1–12.6; p = 0.041). For validation using RNA-seq data as a surrogate, in a population-based SCAN-B cohort (NCT02306096) of 682 consecutive patients receiving adjuvant trastuzumab, the ultrahigh-ERBB2 mRNA group had significantly worse survival. Multiplex ddPCR is useful for ERBB2 CN estimation and ultrahigh ERBB2 may be a predictive factor for decreased long-term survival after trastuzumab treatment.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Dalal, HinaLund University,Lunds universitet,Translational Oncogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital(Swepub:lu)he8535ku
(författare)
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Chen, YilunSAGA Diagnostics AB(Swepub:lu)med-yic
(författare)
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Brueffer, ChristianLund University,Lunds universitet,Translational Oncogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital,SAGA Diagnostics AB(Swepub:lu)med-csb
(författare)
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Gladchuk, SergiiLund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Transl onkogenomik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Transl oncogenomics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital,SAGA Diagnostics AB(Swepub:lu)se1522gl
(författare)
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Alcaide, MiguelSAGA Diagnostics AB
(författare)
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Ehinger, AnnaLund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital,Region Skåne(Swepub:lu)pat-amm
(författare)
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Saal, Lao HLund University,Lunds universitet,Translational Oncogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital(Swepub:lu)onk-ls0
(författare)
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LUCC: Lunds universitets cancercentrumÖvriga starka forskningsmiljöer
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Ingår i:npj Breast Cancer10:12374-4677
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