Prevalence and Outcomes of Germline Pathogenic Variants of Homologous Recombination Repair Genes in Ovarian Cancer

Overview

Journal Cancer Sci

Specialty Oncology

Date 2024 Oct 10

PMID 39385713

Authors

Maiko Miwa

Masakazu Kitagawa

Yuka Asami

Mayumi Kobayashi-Kato

Takafumi Watanabe

Aiko Ogasawara

Kengo Hiranuma

Hisamori Kato

Motonobu Saito

Yohei Miyagi

Tomoyasu Kato

Hiroshi Yoshida

Yukihide Momozawa

Takashi Kohno

Kouya Shiraishi

Kosei Hasegawa

Affiliations

Soon will be listed here.

Abstract

Germline pathogenic variants (PVs) are pivotal in gynecological oncology. We focused on the prevalence, clinicopathological features, and survival impact of homologous recombination repair (HRR) PVs in patients with epithelial ovarian cancer (EOC). This was a multicenter retrospective cohort study, and 1248 patients with EOC were registered. Eligible patients (n = 1112) underwent germline DNA analysis for 26 cancer predisposition genes, including nine HRR-related genes, such as BRCA1/2, BRIP1, PALB2, RAD51C/D, and ATM. The associations between clinicopathological factors and HRR-related PVs were examined. Kaplan-Meier and Cox regression analyses were conducted. Among 1091 analyzed patients, 153 (14.0%) carried PVs and 140 (12.8%) were HRR-related. HRR-PV-positive status significantly correlated with serous carcinoma (22.9% vs. 4.8%, P < 0.0001) and advanced disease (18.5% vs. 5.9%, P < 0.0001). The HRR-PV-positive group exhibited higher prevalence of personal breast (12.9%) and familial breast/ovarian (29.2%) cancer history. HRR status independently improved overall survival in stage III/IV disease (P = 0.04) but not progression-free survival. HRR-related germline PVs exhibit distinct clinicopathological features with survival implications. Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000-2019), the limited use of bevacizumab and poly (ADP-ribose) polymerase inhibitors as maintenance therapy should be recognized.

Citing Articles

Prevalence and outcomes of germline pathogenic variants of homologous recombination repair genes in ovarian cancer.

Miwa M, Kitagawa M, Asami Y, Kobayashi-Kato M, Watanabe T, Ogasawara A Cancer Sci. 2024; 115(12):3952-3962.

PMID: 39385713 PMC: 11611769. DOI: 10.1111/cas.16367.

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