{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["15(9)"],"submitter":["Bartow BB"],"pubmed_abstract":["Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) have demonstrated antitumor activity in cancers with a homologous recombination deficiency (HRD) and have recently been approved by the FDA for the treatment of germline <i>BRCA1/2-</i>mutation-associated breast cancer. PARPis have also been found to be efficacious in <i>BRCA</i> wild-type (<i>BRCAwt</i>) lesions with high genomic loss of heterozygosity (LOH-high). The goal of this study was to retrospectively investigate the tumor mutations in homologous recombination (HRR) genes and the LOH score in advanced-stage breast carcinomas (BCs). Sixty-three patients were included in our study, 25% of whom had HRR gene mutations in their tumors, including 6% <i>BRCA1/2</i> and 19% non-<i>BRCA</i>-containing gene mutations. An HRR gene mutation was associated with a triple-negative phenotype. Twenty-eight percent of the patients had an LOH-high score, which, in turn, was associated with a high histological grade, a triple-negative phenotype, and a high tumor mutational burden (TMB). Among the six patients who received PARPi therapy, one had a tumor with a <i>PALB2</i> mutation other than <i>BRCA</i> and had a clinical partial response. Twenty-two percent of the LOH-low tumors had <i>BRCAwt</i>-HRR gene mutations, compared with 11% of the LOH-high tumors. Comprehensive genomic profiling revealed a subset of breast cancer patients with a <i>BRCAwt</i>-HRR gene mutation that would be missed by an LOH test. The necessity of next-generation sequencing coupled with HRR gene analysis for PARPi therapy requires further investigation in clinical trials."],"journal":["Cancers"],"pagination":["2524"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10177458"],"repository":["biostudies-literature"],"pubmed_title":["Mutations in Homologous Recombination Genes and Loss of Heterozygosity Status in Advanced-Stage Breast Carcinoma."],"pmcid":["PMC10177458"],"pubmed_authors":["Sahin AA","Huo L","Bartow BB","Elkhanany AM","Guo H","Harada S","Huang X","Siegal GP","Ding Q","Magi-Galluzzi C","Yalniz C"],"additional_accession":[]},"is_claimable":false,"name":"Mutations in Homologous Recombination Genes and Loss of Heterozygosity Status in Advanced-Stage Breast Carcinoma.","description":"Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) have demonstrated antitumor activity in cancers with a homologous recombination deficiency (HRD) and have recently been approved by the FDA for the treatment of germline <i>BRCA1/2-</i>mutation-associated breast cancer. PARPis have also been found to be efficacious in <i>BRCA</i> wild-type (<i>BRCAwt</i>) lesions with high genomic loss of heterozygosity (LOH-high). The goal of this study was to retrospectively investigate the tumor mutations in homologous recombination (HRR) genes and the LOH score in advanced-stage breast carcinomas (BCs). Sixty-three patients were included in our study, 25% of whom had HRR gene mutations in their tumors, including 6% <i>BRCA1/2</i> and 19% non-<i>BRCA</i>-containing gene mutations. An HRR gene mutation was associated with a triple-negative phenotype. Twenty-eight percent of the patients had an LOH-high score, which, in turn, was associated with a high histological grade, a triple-negative phenotype, and a high tumor mutational burden (TMB). Among the six patients who received PARPi therapy, one had a tumor with a <i>PALB2</i> mutation other than <i>BRCA</i> and had a clinical partial response. Twenty-two percent of the LOH-low tumors had <i>BRCAwt</i>-HRR gene mutations, compared with 11% of the LOH-high tumors. Comprehensive genomic profiling revealed a subset of breast cancer patients with a <i>BRCAwt</i>-HRR gene mutation that would be missed by an LOH test. The necessity of next-generation sequencing coupled with HRR gene analysis for PARPi therapy requires further investigation in clinical trials.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2025-04-18T13:56:09.591Z","creation":"2025-04-06T23:45:39.467Z"},"accession":"S-EPMC10177458","cross_references":{"pubmed":["37173992"],"doi":["10.3390/cancers15092524"]}}