Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer

Prevalence; Homologous recombination deficiency; Breast cancer

Detalles Bibliográficos
Autores: Romey, Marcel, Llort, Gemma, Torres-Esquius, Sara, Llop-Guevara, Alba, Gutiérrez-Enríquez, Sara, Teule, Alex, Serra, Violeta, Balmaña, Judith
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Departament de Salut de la Generalitat de Catalunya (DS)
Repositorio:Scientia. Dipòsit d'Informació Digital del Departament de Salut
OAI Identifier:oai:scientiasalut.gencat.cat:11351/11391
Acceso en línea:https://hdl.handle.net/11351/11391
Access Level:acceso abierto
Palabra clave:Mama - Càncer - Aspectes genètics
Ovaris - Càncer - Aspectes genètics
Recombinació genètica
Anomalies cromosòmiques
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation::Germ-Line Mutation
PHENOMENA AND PROCESSES::Genetic Phenomena::Recombination, Genetic::Homologous Recombination
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación::mutación de la línea germinal
FENÓMENOS Y PROCESOS::fenómenos genéticos::recombinación genética::recombinación homóloga
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oai_identifier_str oai:scientiasalut.gencat.cat:11351/11391
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer
title Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer
spellingShingle Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer
Romey, Marcel
Mama - Càncer - Aspectes genètics
Ovaris - Càncer - Aspectes genètics
Recombinació genètica
Anomalies cromosòmiques
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation::Germ-Line Mutation
PHENOMENA AND PROCESSES::Genetic Phenomena::Recombination, Genetic::Homologous Recombination
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación::mutación de la línea germinal
FENÓMENOS Y PROCESOS::fenómenos genéticos::recombinación genética::recombinación homóloga
title_short Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer
title_full Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer
title_fullStr Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer
title_full_unstemmed Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer
title_sort Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer
dc.creator.none.fl_str_mv Romey, Marcel
Llort, Gemma
Torres-Esquius, Sara
Llop-Guevara, Alba
Gutiérrez-Enríquez, Sara
Teule, Alex
Serra, Violeta
Balmaña, Judith
author Romey, Marcel
author_facet Romey, Marcel
Llort, Gemma
Torres-Esquius, Sara
Llop-Guevara, Alba
Gutiérrez-Enríquez, Sara
Teule, Alex
Serra, Violeta
Balmaña, Judith
author_role author
author2 Llort, Gemma
Torres-Esquius, Sara
Llop-Guevara, Alba
Gutiérrez-Enríquez, Sara
Teule, Alex
Serra, Violeta
Balmaña, Judith
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Torres-Esquius S, Gutiérrez-Enríquez S] Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Llop-Guevara A] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Translational Medicine, DNA Damage Response Department, AstraZeneca, Barcelona, Spain. [Romey M] Institute of Pathology, Universitätsklinikum Marburg, Marburg, Germany. [Teulé À] Hereditary Cancer Program, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. [Llort G] Department of Medical Oncology, Hospital Universitari Parc Taulí, Sabadell, Spain. [Serra V] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Balmaña J] Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Mama - Càncer - Aspectes genètics
Ovaris - Càncer - Aspectes genètics
Recombinació genètica
Anomalies cromosòmiques
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation::Germ-Line Mutation
PHENOMENA AND PROCESSES::Genetic Phenomena::Recombination, Genetic::Homologous Recombination
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación::mutación de la línea germinal
FENÓMENOS Y PROCESOS::fenómenos genéticos::recombinación genética::recombinación homóloga
topic Mama - Càncer - Aspectes genètics
Ovaris - Càncer - Aspectes genètics
Recombinació genètica
Anomalies cromosòmiques
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation::Germ-Line Mutation
PHENOMENA AND PROCESSES::Genetic Phenomena::Recombination, Genetic::Homologous Recombination
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación::mutación de la línea germinal
FENÓMENOS Y PROCESOS::fenómenos genéticos::recombinación genética::recombinación homóloga
description Prevalence; Homologous recombination deficiency; Breast cancer
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/11391
url https://hdl.handle.net/11351/11391
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv JAMA Network Open;7(4)
https://doi.org/10.1001/jamanetworkopen.2024.7811
info:eu-repo/grantAgreement/ES/PE2017-2020/PI19%2F01303
info:eu-repo/grantAgreement/ES/PEICTI2021-2023/PI22%2F01200
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Medical Association
publisher.none.fl_str_mv American Medical Association
dc.source.none.fl_str_mv Scientia
reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname:Departament de Salut de la Generalitat de Catalunya (DS)
instname_str Departament de Salut de la Generalitat de Catalunya (DS)
reponame_str Scientia. Dipòsit d'Informació Digital del Departament de Salut
collection Scientia. Dipòsit d'Informació Digital del Departament de Salut
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869416862118313984
spelling Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian CancerRomey, MarcelLlort, GemmaTorres-Esquius, SaraLlop-Guevara, AlbaGutiérrez-Enríquez, SaraTeule, AlexSerra, VioletaBalmaña, JudithMama - Càncer - Aspectes genèticsOvaris - Càncer - Aspectes genèticsRecombinació genèticaAnomalies cromosòmiquesDISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian NeoplasmsDISEASES::Neoplasms::Neoplasms by Site::Breast NeoplasmsPHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation::Germ-Line MutationPHENOMENA AND PROCESSES::Genetic Phenomena::Recombination, Genetic::Homologous RecombinationENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricasENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mamaFENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación::mutación de la línea germinalFENÓMENOS Y PROCESOS::fenómenos genéticos::recombinación genética::recombinación homólogaPrevalence; Homologous recombination deficiency; Breast cancerPrevalença; Deficiència de recombinació homòloga; Càncer de mamaPrevalencia; Deficiencia de recombinación homóloga; Cáncer de mamaImportance RAD51C and RAD51D are involved in DNA repair by homologous recombination. Germline pathogenic variants (PVs) in these genes are associated with an increased risk of ovarian and breast cancer. Understanding the homologous recombination deficiency (HRD) status of tumors from patients with germline PVs in RAD51C/D could guide therapeutic decision-making and improve survival. Objective To characterize the clinical and tumor characteristics of germline RAD51C/D PV carriers, including the evaluation of HRD status. Design, Setting, and Participants This retrospective cohort study included 91 index patients plus 90 relatives carrying germline RAD51C/D PV (n = 181) in Spanish hospitals from January 1, 2014, to December 31, 2021. Genomic and functional HRD biomarkers were assessed in untreated breast and ovarian tumor samples (n = 45) from June 2022 to February 2023. Main Outcomes and Measures Clinical and pathologic characteristics were assessed using descriptive statistics. Genomic HRD by genomic instability scores, functional HRD by RAD51, and gene-specific loss of heterozygosity were analyzed. Associations between HRD status and tumor subtype, age at diagnosis, and gene-specific loss of heterozygosity in RAD51C/D were investigated using logistic regression or the t test. Results A total of 9507 index patients were reviewed, and 91 patients (1.0%) were found to carry a PV in RAD51C/D; 90 family members with a germline PV in RAD51C/D were also included. A total of 157 of carriers (86.7%) were women and 181 (55.8%) had received a diagnosis of cancer, mainly breast cancer or ovarian cancer. The most prevalent PVs were c.1026+5_1026+7del (11 of 56 [19.6%]) and c.709C>T (9 of 56 [16.1%]) in RAD51C and c.694C>T (20 of 35 [57.1%]) in RAD51D. In untreated breast cancer and ovarian cancer, the prevalence of functional and genomic HRD was 55.2% (16 of 29) and 61.1% (11 of 18) for RAD51C, respectively, and 66.7% (6 of 9) and 90.0% (9 of 10) for RAD51D. The concordance between HRD biomarkers was 91%. Tumors with the same PV displayed contrasting HRD status, and age at diagnosis did not correlate with the occurrence of HRD. All breast cancers retaining the wild-type allele were estrogen receptor positive and lacked HRD. Conclusions and Relevance In this cohort study of germline RAD51C/D breast cancer and ovarian cancer, less than 70% of tumors displayed functional HRD, and half of those that did not display HRD were explained by retention of the wild-type allele, which was more frequent among estrogen receptor–positive breast cancers. Understanding which tumors are associated with RAD51C/D and HRD is key to identify patients who can benefit from targeted therapies, such as PARP (poly [adenosine diphosphate–ribose] polymerase) inhibitors.This work was funded by Fundación SEOM (Dr Balmaña), Asociación Española de Cáncer de Mama Metastásico (Premio M. Chiara Giorgetti to Dr Balmaña), ERA-Net (RAD51predict, ERAPERMED2019-215 to Dr Serra), Asociación Española Contra el Cáncer (LABAE16020PORTT to Dr Serra and INVES20095LLOP to Dr Llop-Guevara) and LaCaixa Foundation and European Institute of Innovation and Technology/Horizon 2020 (CaixaImpulse grant LCF/TR/CC19/52470003 to Dr Llop-Guevara). Dr Gutiérrez-Enríquez received funding from Spanish Instituto de Salud Carlos III with European Regional Development FEDER Funds (PI19/01303 and PI22/01200); and resources from the Government of Catalonia (2021SGR01112).American Medical AssociationInstitut Català de la Salut[Torres-Esquius S, Gutiérrez-Enríquez S] Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Llop-Guevara A] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Translational Medicine, DNA Damage Response Department, AstraZeneca, Barcelona, Spain. [Romey M] Institute of Pathology, Universitätsklinikum Marburg, Marburg, Germany. [Teulé À] Hereditary Cancer Program, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. [Llort G] Department of Medical Oncology, Hospital Universitari Parc Taulí, Sabadell, Spain. [Serra V] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Balmaña J] Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/11391Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésJAMA Network Open;7(4)https://doi.org/10.1001/jamanetworkopen.2024.7811info:eu-repo/grantAgreement/ES/PE2017-2020/PI19%2F01303info:eu-repo/grantAgreement/ES/PEICTI2021-2023/PI22%2F01200Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/113912026-06-12T09:38:37Z
score 15,811543

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