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
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (35)
- Bray F, "Global cancer statistics 2018 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J Clin, 68, pp.394~424 (2018)
- Kurman RJ, "The origin and pathogenesis of epithelial ovarian cancer : a proposed unifying theory", Am J Surg Pathol, 34, pp.433~443 (2010)
- Levine DA, "Fallopian tube and primary peritoneal carcinomas associated with BRCA mutations", J Clin Oncol, 21, pp.4222~4227 (2003)
- Norquist BM, "Inherited mutations in women with ovarian carcinoma", JAMA Oncol, 2, pp.482~490 (2016)
- Mavaddat N, "Cancer risks for BRCA1 and BRCA2 mutation carriers : results from prospective analysis of EMBRACE", J Natl Cancer Inst, 105, pp.812~822 (2013)
- Kuchenbaecker KB, "Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation Carriers", JAMA, 317, pp.2402~2416 (2017)
- Moore K, "Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer", N Engl J Med, 379, pp.2495~2505 (2018)
- Gonzalez-Martin A, "Niraparib in patients with newly diagnosed advanced ovarian cancer", N Engl J Med, 381, pp.2391~2402 (2019)
- Pujade-Lauraine E, "Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1", 2 mutation(SOLO2, Lancet Oncol, pp.2017, 18[DOI]
- Del Campo JM, "Niraparib maintenance therapy in patients with recurrent ovarian cancer after a partial response to the last platinum-based chemotherapy in the ENGOT-OV16", NOVA trial, 2019, pp.37, 2968~2973
- Ledermann J, "Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer : a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial", Lancet Oncol, 15, pp.852~861 (2014)
- Coleman RL, "Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy(ARIEL3) : a randomised, double-blind, placebo-controlled, phase 3 trial", Lancet, 390, pp.1949~1961 (2017)
- 최민철, "Position statements on genetic test for peritoneal, ovarian, and fallopian tubal cancers: Korean Society of Gynecologic Oncology (KSGO)", Journal of Gynecologic Oncology, 27(4), pp.1~4 (2016), 대한부인종양학회
- Tan DS, "“BRCAness” syndrome in ovarian cancer: a case-control study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations", J Clin Oncol, 26, pp.5530~5536 (2008)
- Alsop K, "BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer : a report from the Australian Ovarian Cancer Study Group", J Clin Oncol, 30, pp.2654~2663 (2012)
- Hyman DM, "Improved survival for BRCA2-associated serous ovarian cancer compared with both BRCA-negative and BRCA1-associated serous ovarian cancer", Cancer, 118, pp.3703~3709 (2012)
- Yang D, "Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer", JAMA, 306, pp.1557~1565 (2011)
- Kim SI, "Effect of BRCA mutational status on survival outcome in advanced-stage high-grade serous ovarian cancer", J Ovarian Res, 12, pp.40~ (2019)
- Park C, "Clinical application of next-generation sequencing-based panel to BRAF wild-type advanced melanoma identifies key oncogenic alterations and therapeutic strategies", Mol Cancer Ther, 19, pp.937~944 (2020)
- Richards S, "Standards and guidelines for the interpretation of sequence variants : a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology", Genet Med, 17, pp.405~424 (2015)
- Eisenhauer EA, "New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)", Eur J Cancer, 45, pp.228~247 (2009)
- Cancer Genome Atlas Research Network, "Integrated genomic analyses of ovarian carcinoma", Nature, 474, pp.609~615 (2011)
- Pennington KP, "Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas", Clin Cancer Res, 20, pp.764~775 (2014)
- Hennessy BT, "Somatic mutations in BRCA1 and BRCA2 could expand the number of patients that benefit from poly(ADP ribose)polymerase inhibitors in ovarian cancer", J Clin Oncol, 28, pp.3570~3576 (2010)
- Hanley GE, "A population-based analysis of germline BRCA1 and BRCA2 testing among ovarian cancer patients in an era of histotype-specific approaches to ovarian cancer prevention", BMC Cancer, 18, pp.254~ (2018)
- 김세익, "Incidence of epithelial ovarian cancer according to histologic subtypes in Korea, 1999 to 2012", Journal of Gynecologic Oncology, 27(1), pp.1~10 (2016), 대한부인종양학회
- Norquist BM, "Mutations in homologous recombination genes and outcomes in ovarian carcinoma patients in GOG 218 : an NRG Oncology", Gynecologic Oncology Group study, 2018, pp.24, 777~783
- Liu Y, "Distinct functions of BRCA1 and BRCA2 in double-strand break repair", Breast Cancer Res, 4, pp.9~13 (2002)
- Gorodnova TV, "High response rates to neoadjuvant platinum-based therapy in ovarian cancer patients carrying germ-line BRCA mutation", Cancer Lett, 369, pp.363~367 (2015)
- Dong F, "A BRCA1", 2mutational signature and survival in ovarian high-grade serous carcinoma, 2016, pp.25, 1511~1516
- Bolton KL, "Association between BRCA1 and BRCA2mutations and survival in women with invasive epithelial ovarian cancer", JAMA, 307, pp.382~390 (2012)
- Lheureux S, "Somatic BRCA1", 2 recovery as a resistance mechanism after exceptional response to poly(ADP-ribose)polymerase inhibition, 2017, pp.35, 1240~1249
- Norquist B, "Secondary somatic mutations restoring BRCA1", 2 predict chemotherapy resistance in hereditary ovarian carcinomas, 2011, pp.29, 3008~3015
- Sokolenko AP, "Rapid selection of BRCA1-proficient tumor cells during neoadjuvant therapy for ovarian cancer in BRCA1 mutation carriers", Cancer Lett, 397, pp.127~132 (2017)
- Eoh KJ, "Mutation landscape of germline and somatic BRCA1", 2 in patients with high-grade serous ovarian cancer, 2020, pp.20, 204~