Implementing HRD Testing in Routine Clinical Practice on Patients with Primary High-Grade Advanced Ovarian Cancer

Florian Heitz; Beyhan Ataseven; Claudia Staniczok; Carsten Denkert; Kerstin Rhiem; Eric Hahnen; Sebastian Heikaus; Malak Moubarak; Julia Welz; Timoleon Dagres; Vasilios Vrentas; Mareike Bommert; Stephanie Schneider; Nicole Concin; Philipp Harter

doi:10.3390/cancers15030818

Implementing HRD Testing in Routine Clinical Practice on Patients with Primary High-Grade Advanced Ovarian Cancer

Cancers (Basel). 2023 Jan 29;15(3):818. doi: 10.3390/cancers15030818.

Authors

Florian Heitz^{1

2}, Beyhan Ataseven^{1

3}, Claudia Staniczok^{1

3}, Carsten Denkert⁴, Kerstin Rhiem⁵, Eric Hahnen⁵, Sebastian Heikaus⁶, Malak Moubarak¹, Julia Welz¹, Timoleon Dagres¹, Vasilios Vrentas¹, Mareike Bommert¹, Stephanie Schneider¹, Nicole Concin¹, Philipp Harter¹

Affiliations

¹ Klinik für Gynäkologie und Gynäkologische Onkologie, Evangelische Kliniken Essen Mitte, 45136 Essen, Germany.
² Klinik für Gynäkologie mit dem Center für Onkologische Operative Therapie, Charité Campus, Virchowklinikum, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institut of Health, 13353 Berlin, Germany.
³ Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 81675 Munich, Germany.
⁴ Institut für Pathologie, Universitätsklinik Marburg, Philipps-Universität Marburg, 35043 Marburg, Germany.
⁵ Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, 50937 Cologne, Germany.
⁶ Zentrum für Pathologie Evangelische Kliniken Essen Mitte, 45136 Essen, Germany.

Abstract

The chemotherapy backbone for patients with high-grade advanced epithelial ovarian cancer (HG-AOC) is carboplatin and paclitaxel followed by a maintenance therapy either with bevacizumab, with a PARP inhibitor, or with a combination of both, which is defined by the presence of a homologous recombination deficiency (HRD) and by the BRCA1/2 status. This study included patients with a primary diagnosis of HG-AOC treated between December 2019 and December 2021. The HRD status was measured using the Myriad myChoice^® test on all the patients with an indication for tumor HRD testing. Germline testing was conducted on all the patients using the TruRisk^® panel as recommended by the national guidelines. HRD testing was requested for 190 patients, and, for 163 patients (85.8%), an HRD test result was available. An HRD test result could not be reported in 27 patients due to an insufficient tumor yield. The median time that it took to receive the HRD test results was 37 days (range of 8-97). In total, an HRD was present in 44.7% (73/163) of the patients based on a GIS ≥ 42 in 42.9% of the patients and based on a tumor BRCA1/2 mutation in 3 cases (all with a GIS < 42). The germline testing results were available for 148 patients, and, in 18 patients (12.2%), a deleterious germline mutation was detected. Of the 27 patients without sufficient HRD testing, BRCA1/2 germline testing results were available for 19 patients (70.4%), and a deleterious germline mutation was detected in 2 patients (7.4%). The implementation of HRD testing is feasible, and the results become available for treatment decisions in a timely manner for most patients. The prerequisite for HRD testing with the Myriad myChoice^® test is a sufficient amount of tumor tissue. The cotesting of HRD and BRCA1/2 germline testing should be aimed for in order to enable optimal and timely treatment decisions on maintenance therapy as well as to test patients on whom the HRD test will not be evaluable.

Keywords: BRCA1/2; PARP inhibitor; homologue recombination deficiency; primary high-grade advanced ovarian cancer; tumor testing.

Grants and funding

This research received no external funding.