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Background: Poly-ADP ribose polymerase inhibitors have been shown to improve progression-free survival in patients with advanced high-grade epithelial non-mucinous ovarian cancers characterized by a deficiency in homologous recombination (HRD). Guidelines recommend all patients with advanced high-grade epithelial ovarian cancer undergo genomic tumor testing for HRD. Our aim was to evaluate the first year of HRD testing at the statewide Western Australia Gynecologic Cancer Service to assess factors associated with obtaining a diagnostic HRD testing result.
Methods: Retrospective chart review.
Results: HRD testing was indicated in 84 patients, and ordered in 79, of which three had non-diagnostic/inconclusive results, all due to insufficient tumor quantity. One patient had the sample collected using a 20-gauge core biopsy needle under image guidance, one patient following interval debulking surgery, and one following primary debulking surgery. Of 76 patients with an HRD result, HRD was positive in 29 (38.2%). A somatic BRCA mutation was detected in six of these 29 patients (20.6%) and HRD positive, BRCAwt was detected in 23 of 29 patients (79.4%). All core biopsies with 16- and 18-gauge needles had a diagnostic HRD result. Ten of 11 patients who were treated by neoadjuvant chemotherapy and whose biopsies were obtained at interval cytoreductive surgery had sufficient tumor tissue for testing and had a diagnostic HRD result. All ascitic/pleural fluid samples sent for HRD testing yielded diagnostic results.
Conclusions: Compliance with HRD testing was high, and only three of 79 (3.8%) patients had non-diagnostic results.
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http://dx.doi.org/10.1002/cnr2.70335 | DOI Listing |
Cancer Epidemiol Biomarkers Prev
September 2025
Emory University, Atlanta, GA, United States.
Background: Half of ovarian high-grade serous carcinomas (HGSC) have homologous recombination deficiency (HRD). However, HRD is not well-characterized in Black individuals who experience worse survival after a diagnosis of HGSC. The objective of this study was to characterize ovarian HGSC HRD and examine its association with survival by self-reported race.
View Article and Find Full Text PDFCancer Rep (Hoboken)
September 2025
Western Australia Gynaecological Cancer Service, King Edward Memorial Hospital, Subiaco, Western Australia, Australia.
Background: Poly-ADP ribose polymerase inhibitors have been shown to improve progression-free survival in patients with advanced high-grade epithelial non-mucinous ovarian cancers characterized by a deficiency in homologous recombination (HRD). Guidelines recommend all patients with advanced high-grade epithelial ovarian cancer undergo genomic tumor testing for HRD. Our aim was to evaluate the first year of HRD testing at the statewide Western Australia Gynecologic Cancer Service to assess factors associated with obtaining a diagnostic HRD testing result.
View Article and Find Full Text PDFBr J Cancer
August 2025
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Background: Because breast cancer (BC) is molecularly heterogeneous, diagnosis and treatment will likely benefit from comprehensive genetic profiling. However, routine, high-resolution sequencing is not feasible yet, due to implementation challenges associated with whole-genome sequencing of formalin-fixed paraffin embedded (FFPE) BC samples. Therefore, we explored the potential of an alternative low-resolution, genome-wide testing approach that is able to capture the copy number (CN) landscape, including actionable alterations, in FFPE derived DNA.
View Article and Find Full Text PDFBiomark Res
August 2025
National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Homologous recombination deficiency (HRD) is a common characteristic of human cancers, which occurs most frequently in ovarian and breast cancers. The unique genetic vulnerabilities, coupled with the synthetic lethality effect of Poly-(ADP-ribose) polymerase (PARP) inhibitors (PARPi), provide a promising opportunity for targeting HRD cancers. However, only a few HRD patients benefit from PARPi monotherapy, and it is therefore imperative to explore effective combination therapies for HRD tumors.
View Article and Find Full Text PDFInt J Clin Oncol
August 2025
Department of Breast Surgery and Oncology, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan.
Hereditary breast and ovarian cancer (HBOC) syndrome is caused by germline mutations in the BRCA1 and BRCA2 genes, which play critical roles in DNA double-strand break repair. Pathogenic variants (PVs) in these genes lead to homologous recombination deficiency (HRD), genomic instability, and increased cancer risk. BRCA1-associated breast cancers are predominantly triple-negative breast cancer (TNBC) with aggressive behavior, and BRCA2-mutated cases are mostly hormone receptor-positive and share similarities with sporadic luminal tumors.
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