BRCA Mutation Status to Personalize Management of Recurrent Ovarian Cancer: A Multicenter Study

Abstract

Recurrent ovarian cancer BRCAmut patients have the best prognosis regardless of SCS, whereas PRS in BRCAwt women can improve when complete SCS is performed. The identification and incorporation of predictive biomarkers such as BRCA status to tailor the medical and surgical approach is paramount to the success of recurrent HGSOC treatments.

Molecular profiles of BRCA1‐associated ovarian cancer treated by platinum‐based therapy: Analysis of primary, residual and relapsed tumors

“…1,2 Molecular pathogenesis of BRCA1/2-driven OC usually involves somatic inactivation of the remaining BRCA1/2 allele in the tumor tissue resulting in tumor-specific deficiency in DNA repair by homologous recombination. 1,2 Molecular pathogenesis of BRCA1/2-driven OC usually involves somatic inactivation of the remaining BRCA1/2 allele in the tumor tissue resulting in tumor-specific deficiency in DNA repair by homologous recombination.…”

“…1,2 Molecular pathogenesis of BRCA1/2-driven OC usually involves somatic inactivation of the remaining BRCA1/2 allele in the tumor tissue resulting in tumor-specific deficiency in DNA repair by homologous recombination. 2,5 Molecular mechanisms of acquired resistance of BRCA1/2-associated cancers to systemic therapy have been studied in detail. Despite initial response to the primary systemic treatment, virtually all OC patients with advanced disease eventually relapse.…”

“…Introduction BRCA1/2 germline mutations are responsible for 15-30% of the incidence of high-grade serous ovarian cancer (OC). 1,2 Molecular pathogenesis of BRCA1/2-driven OC usually involves somatic inactivation of the remaining BRCA1/2 allele in the tumor tissue resulting in tumor-specific deficiency in DNA repair by homologous recombination. 3,4 As a result, hereditary OC commonly demonstrates increased sensitivity to platinum compounds and poly(ADP-ribose) polymerase inhibitors (PARPi).…”

“…Despite initial response to the primary systemic treatment, virtually all OC patients with advanced disease eventually relapse. 2,5 Molecular mechanisms of acquired resistance of BRCA1/2-associated cancers to systemic therapy have been studied in detail. The most known event associated with the cessation of the effect of platinum compounds and PARPi is a gain of secondary BRCA1/2 mutation, which is located in the vicinity to the germline DNA sequence alteration and restores the open reading frame (ORF) of the affected allele.…”

Oral Squamous Cell Carcinoma as a Complication of Treatment for Recurrent High‐Grade Serous Cancer

“…In contrast, approximately 10% to 18% of ovarian cancer cases in the US are attributable to BRCA mutations, 12 with mutations present in 40% of patients with recurrent ovarian cancer. 13 Unfortunately, we do not know the BRCA status for the eight patients treated with PLD who did not develop oral SCC and cannot draw any specific conclusions from these data; however it is an interesting observation that deserves investigation in future studies. It is known that the presence of a BRCA mutation is associated with better survival in patients with high-grade serous ovarian cancer, 14 which may partially explain why such a high percentage of patients developing oral cavity SCC are BRCA 1/2+ as these patients are more likely to live long enough to develop a secondary malignancy.…”