{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bonnet E"],"funding":["French National Cancer Institute","EURACAN","LABEX DevweCAN","CSRD VA","Bpifrance"],"pagination":["1595"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9604780"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(10)"],"pubmed_abstract":["<h4>Background</h4>a specific subset of metastatic triple-negative breast cancers (mTNBC) is characterized by homologous recombination deficiency (HRD), leading to enhanced sensitivity to platinum-based chemotherapy. Apart from mutations in <i>BRCA1/2</i> genes, the evaluation of other HRD-related alterations has been limited to date. As such, we analyzed data from mTNBC patients enrolled in the ProfiLER-01 study to determine the prevalence of alterations in homologous recombination-related (HRR) genes and their association with platinum sensitivity.<h4>Methods</h4>next-generation sequencing and promoter methylation of <i>BRCA1</i> and <i>RAD51C</i> were performed on tumors from patients with mTNBC, using a panel of 19 HRR genes. Tumors were separated into three groups based on their molecular status: mutations in <i>BRCA1/2</i>, mutations in other HRR genes (<i>BRCA1/2</i> excluded) or <i>BRCA1/RAD51C</i> promoter methylation and the absence of molecular alterations in HRR genes (groups A, B and C, respectively). Sensitivity to platinum-based chemotherapy was evaluated through the radiological response.<h4>Results</h4>mutations in <i>BRCA1/2</i> were detected in seven (13.5%) patients, while alterations in other HRR genes or hypermethylation in <i>BRCA1</i> or <i>RAD51C</i> were reported in 16 (30.7%) patients; furthermore, no alteration was found in the majority of patients (<i>n</i> = 29; 55.8%). Among 27 patients who received platinum-based chemotherapy, the disease control rate was 80%, 55% and 18% (groups A, B and C, respectively; <i>p</i> = 0.049). Regarding group B, patients with disease control exhibited mutations in <i>FANCL</i>, <i>FANCA</i> and the <i>RAD51D</i> genes or <i>RAD51C</i> methylation; Conclusion: mutations in HRR genes and epimutations in <i>RAD51C</i> were associated with disease control through platinum-based chemotherapy. As such, apart from well-characterized alterations in <i>BRCA1/2</i>, a more comprehensive evaluation of HRD should be considered in order to enlarge the selection of patients with mTNBC that could benefit from platinum-based chemotherapy."],"journal":["Journal of personalized medicine"],"pubmed_title":["Alterations in Homologous Recombination-Related Genes and Distinct Platinum Response in Metastatic Triple-Negative Breast Cancers: A Subgroup Analysis of the ProfiLER-01 Trial."],"pmcid":["PMC9604780"],"funding_grant_id":["1","ANR-10-LABX-0061","DGOS-INCA-4664","EU project 739521","E8983-PREDICTIV"],"pubmed_authors":["Pissaloux D","Toussaint P","Paindavoine S","Sohier E","Lasset C","Lardy-Cleaud A","Wang Q","Combaret V","Bonnet E","Haddad V","Heudel PE","Viari A","Bonadona V","Eberst L","Treilleux I","Attignon V","Tredan O","Baffert KA","Dufresne A","Ray-Coquard I","Buisson A","Quesada S","Perol D","Blay JY","Bachelot T"],"additional_accession":[]},"is_claimable":false,"name":"Alterations in Homologous Recombination-Related Genes and Distinct Platinum Response in Metastatic Triple-Negative Breast Cancers: A Subgroup Analysis of the ProfiLER-01 Trial.","description":"<h4>Background</h4>a specific subset of metastatic triple-negative breast cancers (mTNBC) is characterized by homologous recombination deficiency (HRD), leading to enhanced sensitivity to platinum-based chemotherapy. Apart from mutations in <i>BRCA1/2</i> genes, the evaluation of other HRD-related alterations has been limited to date. As such, we analyzed data from mTNBC patients enrolled in the ProfiLER-01 study to determine the prevalence of alterations in homologous recombination-related (HRR) genes and their association with platinum sensitivity.<h4>Methods</h4>next-generation sequencing and promoter methylation of <i>BRCA1</i> and <i>RAD51C</i> were performed on tumors from patients with mTNBC, using a panel of 19 HRR genes. Tumors were separated into three groups based on their molecular status: mutations in <i>BRCA1/2</i>, mutations in other HRR genes (<i>BRCA1/2</i> excluded) or <i>BRCA1/RAD51C</i> promoter methylation and the absence of molecular alterations in HRR genes (groups A, B and C, respectively). Sensitivity to platinum-based chemotherapy was evaluated through the radiological response.<h4>Results</h4>mutations in <i>BRCA1/2</i> were detected in seven (13.5%) patients, while alterations in other HRR genes or hypermethylation in <i>BRCA1</i> or <i>RAD51C</i> were reported in 16 (30.7%) patients; furthermore, no alteration was found in the majority of patients (<i>n</i> = 29; 55.8%). Among 27 patients who received platinum-based chemotherapy, the disease control rate was 80%, 55% and 18% (groups A, B and C, respectively; <i>p</i> = 0.049). Regarding group B, patients with disease control exhibited mutations in <i>FANCL</i>, <i>FANCA</i> and the <i>RAD51D</i> genes or <i>RAD51C</i> methylation; Conclusion: mutations in HRR genes and epimutations in <i>RAD51C</i> were associated with disease control through platinum-based chemotherapy. As such, apart from well-characterized alterations in <i>BRCA1/2</i>, a more comprehensive evaluation of HRD should be considered in order to enlarge the selection of patients with mTNBC that could benefit from platinum-based chemotherapy.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2024-12-03T15:38:35.366Z","creation":"2024-12-03T15:38:35.366Z"},"accession":"S-EPMC9604780","cross_references":{"pubmed":["36294734"],"doi":["10.3390/jpm12101595"]}}