Introduction In recent years, promising survival benefits from maintenance therapy with poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) has changed the management of epithelial ovarian cancer (EOC) in newly diagnosed and recurrent disease. Identification of BRCA and/or homologous recombination (HR) gene mutation is critical for selecting patients for PARPi treatment and as a prognostic and predictive biomarker in high-grade serous carcinoma (HGSOC), yet its role in other histology remains controversial. Our study aims to retrospectively analyze the correlation of BRCA/HR gene mutation with the clinical outcomes of EOC patients.
Methods 318 women diagnosed with EOC who had received debulking surgery and platinum-based adjuvant chemotherapy at NTUH were retrospectively reviewed. The tumor tissue was sent for genetic analysis for somatic mutation of genes in HR gene panel, including BRCA 1/2. Clinical data were obtained from medical records.
Results 25.4% of patients with HGSOC (n = 177) had BRCA/HR mutation and showed better sensitivity to platinum-based chemotherapy (83.9% vs. 69.5%, P=0.029) and longer progression-free survival (PFS) (P=0.004 and <0.001, respectively). However, only 7.8% of patients with non-serous histology had BRCA/HR mutation and showed no correlation with platinum sensitivity, PFS, or overall survival. Through the multivariate analysis, we confirmed the protective effect of BRCA/HR mutation with disease recurrence and death in patients with HGSOC yet no effect was found on non-serous histologic type.
Conclusion/Implications BRCA/HR mutation is a prognostic biomarker in HGSOC yet not in non-serous patients. Further study is needed to follow up on the clinical response to PARPi in these patients and find out other proper prognostic biomarkers.
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