BRCA-negative high-grade serous ovarian cancer with recurrent progression: A clinical case

Abstract

Relevance: High-grade serous ovarian cancer (HGSOC) is characterized by pronounced genomic instability, frequent mutations in BRCA1/2 genes, and high clinical and molecular heterogeneity. In some patients, the disease is accompanied by a homologous recombination deficiency (HRD), which causes sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. However, the efficacy of these drugs remains limited in BRCA wild-type patients.
This study aimed to analyze and describe a clinical case of BRCA-negative serous ovarian cancer complicated by multiple progressions and the formation of drug resistance.
Methods: This study presents a clinical case of a patient with a common form of HGSOC, without mutations in BRCA1/2 genes but with a moderately positive HRD status. Molecular genetic analysis was performed by next-generation sequencing using the Foundation Medicine platform. The effectiveness of the treatment was assessed through positron emission tomography combined with computed tomography, magnetic resonance imaging, and computed tomography, alongside serial measurements of the CA-125 tumor marker.
Results: The patient underwent cytoreductive surgery followed by five successive lines of chemotherapy, including platinum-based regimens, bevacizumab, liposomal doxorubicin, gemcitabine, and оlaparib as a PARP inhibitor. Although transient partial responses were achieved, the disease subsequently progressed. Molecular genetic analysis confirmed the absence of BRCA1/2 mutations and revealed an HRD score of 20.1%, indicative of limited sensitivity to PARP inhibition. As the patient’s general condition declined, a transition to palliative care was initiated in February 2025. The patient passed away in March 2025.
Conclusions: The presented case highlights the limited therapeutic possibilities in BRCA-negative HGSOC with moderate HRD status and demonstrates the need to develop new personalized treatment strategies in patients with an unfavorable molecular profile