Show simple item record

dc.contributor.authorYndestad, Synnøve
dc.contributor.authorEngebrethsen, Christina
dc.contributor.authorHerencia-Ropero, A.
dc.contributor.authorNikolaienko, Oleksii
dc.contributor.authorVintermyr, Olav Karsten
dc.contributor.authorLillestøl, Reidun Kristine
dc.contributor.authorMinsaas, Laura
dc.contributor.authorLeirvaag, Beryl
dc.contributor.authorIversen, Gjertrud Titlestad
dc.contributor.authorGilje, Bjørnar
dc.contributor.authorBlix, Egil Støre
dc.contributor.authorEspelid, Helge
dc.contributor.authorLundgren, Steinar
dc.contributor.authorGeisler, Jürgen
dc.contributor.authorAase, Hildegunn Siv
dc.contributor.authorAas, Turid
dc.contributor.authorGudlaugsson, Einar
dc.contributor.authorLlop-Guevara, Alba
dc.contributor.authorSerra, Violeta
dc.contributor.authorJanssen, Emiel
dc.contributor.authorLønning, Per Eystein
dc.contributor.authorKnappskog, Stian
dc.contributor.authorEikesdal, Hans Petter
dc.date.accessioned2024-02-14T13:48:36Z
dc.date.available2024-02-14T13:48:36Z
dc.date.issued2023-12-01
dc.description.abstractPurpose - Homologous recombination deficiency (HRD) is highly prevalent in triple-negative breast cancer (TNBC) and associated with response to PARP inhibition (PARPi). Here, we studied the prevalence of HRD in non-TNBC to assess the potential for PARPi in a wider group of patients with breast cancer.<p> <p>Methods - HRD status was established using targeted gene panel sequencing (360 genes) and BRCA1 methylation analysis of pretreatment biopsies from 201 patients with primary breast cancer in the phase II PETREMAC trial (ClinicalTrials.gov identifier: NCT02624973). HRD was defined as mutations in BRCA1, BRCA2, BRIP1, BARD1, or PALB2 and/or promoter methylation of BRCA1 (strict definition; HRD-S). In secondary analyses, a wider definition (HRD-W) was used, examining mutations in 20 additional genes. Furthermore, tumor BRCAness (multiplex ligation-dependent probe amplification), PAM50 subtyping, RAD51 nuclear foci to test functional HRD, tumor-infiltrating lymphocyte (TIL), and PD-L1 analyses were performed.<p> <p>Results - HRD-S was present in 5% of non-TNBC cases (n = 9 of 169), contrasting 47% of the TNBC tumors (n = 15 of 32). HRD-W was observed in 23% of non-TNBC (n = 39 of 169) and 59% of TNBC cases (n = 19 of 32). Of 58 non-TNBC and 30 TNBC biopsies examined for RAD51 foci, 4 of 4 (100%) non-TNBC and 13 of 14 (93%) TNBC cases classified as HRD-S had RAD51 low scores. In contrast, 4 of 17 (24%) non-TNBC and 15 of 19 (79%) TNBC biopsies classified as HRD-W exhibited RAD51 low scores. Of nine non-TNBC tumors with HRD-S status, only one had a basal-like PAM50 signature. There was a high concordance between HRD-S and either BRCAness, high TIL density, or high PD-L1 expression (each P < .001).<p> <p>Conclusion - The prevalence of HRD in non-TNBC suggests that therapy targeting HRD should be evaluated in a wider breast cancer patient population. Strict HRD criteria should be implemented to increase diagnostic precision with respect to functional HRD.en_US
dc.identifier.citationYndestad, Engebrethsen, Herencia-Ropero, Nikolaienko, Vintermyr OK, Lillestøl, Minsaas, Leirvaag, Iversen GT, Gilje, Blix ES, Espelid, Lundgren, Geisler J, Aase HS, Aas T, Gudlaugsson E, Llop-Guevara, Serra, Janssen, Lønning PE, Knappskog, Eikesdal HP. Homologous Recombination Deficiency Across Subtypes of Primary Breast Cancer. JCO Precision Oncology (JCO PO). 2023;7(7)en_US
dc.identifier.cristinIDFRIDAID 2235116
dc.identifier.doi10.1200/PO.23.00338
dc.identifier.issn2473-4284
dc.identifier.urihttps://hdl.handle.net/10037/32932
dc.language.isoengen_US
dc.publisherAmerican Society for Clinical Oncologyen_US
dc.relation.journalJCO Precision Oncology (JCO PO)
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)en_US
dc.titleHomologous Recombination Deficiency Across Subtypes of Primary Breast Canceren_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


File(s) in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)