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

• DOI: 10.1001/jamanetworkopen.2024.7811
• Publication Date: 2024-04-22T15:32:12Z
• Authors: Sara Torres-Esquius; Alba Llop-Guevara; Sara Gutiérrez-En...; Marcel Romey; Àlex Teulé; Gemma Llort; Ana Herrero; Pilar Sánchez-Hen...; Anna Vallmajó; Santiago González...; Isabel Chirivella; Juana Maria Cano; Begoña Graña; Sara Simonetti; Isabela Díaz de C...; Teresa Ramon y Cajal; Judit Sanz; Sara Serrano; Andrea Otero; Cristina Churruca; Ana Beatriz Sánch...; Sonia Servitja; Carmen Guillén-Ponce; Joan Brunet; Carsten Denkert; Violeta Serra; Judith Balmaña
• Keywords: 03 medical and health sciences; 0302 clinical medicine; Original Investigation

Importance RAD51C and RAD51D are involved in DNA repair by homologous recombination. Germline pathogenic variants (PVs) these genes associated with an increased risk of ovarian breast cancer. Understanding the recombination deficiency (HRD) status tumors from patients germline PVs RAD51C/D could guide therapeutic decision-making improve survival. Objective To characterize clinical tumor characteristics PV carriers, including evaluation HRD status. Design, Setting, Participants This retrospective cohort study included 91 index plus 90 relatives carrying (n = 181) Spanish hospitals January 1, 2014, to December 31, 2021. Genomic functional biomarkers were assessed untreated samples 45) June 2022 February 2023. Main Outcomes Measures Clinical pathologic using descriptive statistics. genomic instability scores, RAD51, gene-specific loss heterozygosity analyzed. Associations between subtype, age at diagnosis, investigated logistic regression or t test. Results A total 9507 reviewed, (1.0%) found carry a ; family members also included. 157 carriers (86.7%) women 181 (55.8%) had received diagnosis cancer, mainly cancer The most prevalent c.1026+5_1026+7del (11 56 [19.6%]) c.709C>T (9 [16.1%]) c.694C>T (20 35 [57.1%]) . In prevalence was 55.2% (16 29) 61.1% 18) for , respectively, 66.7% (6 9) 90.0% 10) concordance 91%. Tumors same displayed contrasting status, did not correlate occurrence HRD. All cancers retaining wild-type allele estrogen receptor positive lacked Conclusions Relevance this less than 70% HRD, half those that display explained retention allele, which more frequent among receptor–positive cancers. is key identify who can benefit targeted therapies, such as PARP (poly [adenosine diphosphate–ribose] polymerase) inhibitors.