Facts, Views & Vision
in ObGyn

Journal of the European Society for Gynaecological Endoscopy

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Homologous recombination repair deficiency (HRD) testing in newly diagnosed advanced-stage epithelial ovarian cancer: A Belgian expert opinion

I. Vergote 1, H. Denys 2, S. Altintas 3, J. Kerger 4,5, J-F. Baurain 6, V. Bours 7, S. Henry 4, K. Van de Vijver 8,9, D. Lambrechts 10, C. Gennigens 11

1 Department of Gynaecological Oncology, University Hospitals Leuven, Leuven Cancer Institute, Herestraat 49, 3000 Leuven, Belgium
2 Department of Medical Oncology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium
3 Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, 2650 Edegem, Belgium
4 Department of Medical Oncology in the SORMN, CHU UCL Namur, Place Louise Godin 15, 5000 Namur, Belgium
5 Jules Bordet Institute, Brussels University Hospital, Université Libre de Bruxelles, Boulevard de Waterloo 121, 1000 Brussels, Belgium
6 Department of Medical Oncology, Cliniques Universitaires Saint-Luc, UCLouvain, avenue Hippocrate 10, 1200 Brussels, Belgium
7 Department of Human Genetics, CHU Liège, 4000 Liège, Belgium
8 Department of Pathology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium
9 Department of Pathological Anatomy, Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Belgium
10 Laboratory of Translational Genetics (VIB-KU Leuven), ON IV Herestraat 49 - box 912, 3000 Leuven, Belgium
11 Department of Medical Oncology, Liège University Hospital, Avenue de l’Hôpital 1, 4000 Liège, Belgium

Keywords:

HRR deficiency, genomic instability, advanced ovarian cancer, PARPi


Published online: Jul 01 2022

https://doi.org/10.52054/FVVO.14.2.024

Abstract

Ovarian cancer (OC) has a poor prognosis as most patients present with non-specific symptoms and the disease is mostly diagnosed at advanced stages. Approximately 90% of cases are classified as epithelial OC (EOC), a category comprising histologically and molecularly distinct tumours. Identifying reliable biomarkers and employing personalised therapies in OC subgroups is crucial for battling the disease. EOCs are often characterised by homologous recombination repair deficiency (HRD), frequently caused by inactivation of the breast cancer susceptibility (BRCA) genes. These findings have led to the development of poly- (adenosine diphosphate [ADP])- ribose polymerase inhibitors (PARPi), which are synthetically lethal to HRD tumour cells. Both patients with HRD and non-HRD tumours can benefit from PARPi therapy in the recurrent setting. Moreover, recent phase III trials in patients with newly diagnosed advanced-stage OC have demonstrated greater clinical benefit from PARPi in treating HRD than non-HRD tumours. These findings offer new opportunities for the use of PARPi as maintenance therapy after first-line chemotherapy based on the presence of HRD. In the current article, we provide recommendations for HRD testing and treatment of patients with newly diagnosed advanced-stage EOC.