Cancer Res Treat.  2020 Oct;52(4):1229-1241. 10.4143/crt.2020.557.

Germline and Somatic BRCA1/2 Gene Mutational Status and Clinical Outcomes in Epithelial Peritoneal, Ovarian, and Fallopian Tube Cancer: Over a Decade of Experience in a Single Institution in Korea

• Kim SI
• Lee M
• Kim HS
• Chung HH
• Kim JW
• Park NH
• Song YS

• KMID: 2507948
• DOI: http://doi.org/10.4143/crt.2020.557

Abstract

Purpose
This study aimed to present a single institutional experience with BRCA1/2 gene tests and the effects of pathogenic mutations in epithelial peritoneal, ovarian, and fallopian tube cancer (POFTC) on survival outcomes.
Materials and Methods
We identified patients with epithelial POFTCs who underwent BRCA1/2 gene testing by either germline or somatic methods between March 2007 and March 2020. Based on the BRCA1/2 test results, patients were divided into BRCA mutation and wild-type groups, followed by comparisons of clinicopathologic characteristics and survival outcomes after primary treatment.
Results
The annual number of POFTC patients who received BRCA1/2 gene tests increased gradually. In total, 511 patients were included and BRCA1/2 mutations were observed in 143 (28.0%). Among 57 patients who received both germline and somatic tests, three (5.3%) showed discordant results from the two tests. Overall, no differences in progression-free survival (PFS; p=0.467) and overall survival (p=0.641) were observed between the BRCA mutation and wild-type groups; however, multivariate analyses identified BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted hazard ratio [aHR], 0.765; 95% confidence interval [CI], 0.593 to 0.987; p=0.040). In 389 patients with International Federation of Gynecology and Obstetrics stage III-IV, different results were shown depending on primary treatment strategy: while BRCA1/2 mutation significantly improved PFS in the subgroup of neoadjuvant chemotherapy (aHR, 0.619; 95% CI, 0.385 to 0.995; p=0.048), it did not affect patient PFS in the subgroup of primary debulking surgery (aHR, 0.759; 95% CI, 0.530 to 1.089; p=0.135).
Conclusion
BRCA1/2 mutations are frequently observed in patients with epithelial POFTCs, and such patients showed better PFS than did those harboring wild-type BRCA1/2.

Keyword

Genital neoplasms; Female; Ovarian neoplasms; Germline test; Somatic test; mutation; Clinical outcome; Survival outcome

Figure

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  Fig. 1. Annual number of BRCA1/2 gene tests among patients with peritoneal, ovarian, and fallopian tube cancers (POFTCs) and according to changes in sociomedical environment in Korea. NHIS, National Health Insurance Service; RRSO, risk reducing salpingo-oophorectomy; KFDA, Korea Food and Drug Administration; PSR, platinum-sensitive relapsed; HGS, high-grade serous; KSGO, Korean Society of Gynecologic Oncology; NGS, next-generation sequencing; HG, high-grade; HRDpos, homologous recombination deficiency-positive.

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  Fig. 2. Aerial chart depicting proportion of patients who underwent germline and somatic BRCA1/2 gene tests along with the test results.

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  Fig. 3. Survival outcomes of the study population (A, B), and further comparisons according to the mutated BRCA gene (C, D). (A, C) Progression-free survival (PFS). (B, D) Overall survival (OS).

Reference

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