Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients
2
조회
0
다운로드
7
인용
0
참고문헌
키워드
초록
Purpose The purpose of this study was to investigate the clinical features of epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status (mutation, variant of uncertain significance [VUS], or wild type). Materials and Methods We analyzed 116 patients whose BRCA1/2 genetic test results were available for mutation type and clinical features, including progression-free survival (PFS), overall survival (OS), and response rate. These characteristics were compared according to BRCA1/2 mutation status. Results Thirty-seven (37/116, 31.9%) BRCA1/2mutations were identified (BRCA1, 30; BRCA2, 7). Mutation of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients (5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal histories of breast cancer were observed in 48.6% of patients with BRCA1/2 mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively). Conclusion Patients with BRCA1/2mutation had longer OS than those with BRCA1/2wild type. Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.
Abstract
Purpose The purpose of this study was to investigate the clinical features of epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status (mutation, variant of uncertain significance [VUS], or wild type). Materials and Methods We analyzed 116 patients whose BRCA1/2 genetic test results were available for mutation type and clinical features, including progression-free survival (PFS), overall survival (OS), and response rate. These characteristics were compared according to BRCA1/2 mutation status. Results Thirty-seven (37/116, 31.9%) BRCA1/2mutations were identified (BRCA1, 30; BRCA2, 7). Mutation of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients (5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal histories of breast cancer were observed in 48.6% of patients with BRCA1/2 mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively). Conclusion Patients with BRCA1/2mutation had longer OS than those with BRCA1/2wild type. Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.
참고문헌 (29)
- 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
- Ramus SJ, "The contribution of BRCA1 and BRCA2 to ovarian cancer", Mol Oncol, 3, pp.138~150 (2009)
- Chen S, "Characterization of BRCA1 and BRCA2 mutations in a large United States sample", J Clin Oncol, 24, pp.863~871 (2006)
- 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)
- Sun C, "The role of BRCA status on the prognosis of patients with epithelial ovarian cancer: a systematic review of the literature with a meta-analysis", PLoS One, 9, pp.e95285~ (2014)
- Levine DA, "Cell proliferation and apoptosis in BRCA-associated hereditary ovarian cancer", Gynecol Oncol, 85, pp.431~434 (2002)
- McLaughlin JR, "Long-term ovarian cancer survival associated with mutation in BRCA1 or BRCA2", J Natl Cancer Inst, 105, pp.141~148 (2013)
- Kotsopoulos J, "Ten-year survival after epithelial ovarian cancer is not associated with BRCA mutation status", Gynecol Oncol, 140, pp.42~47 (2016)
- Johannsson OT, "Survival of BRCA1 breast and ovarian cancer patients : a population-based study from southern Sweden", J Clin Oncol, 16, pp.397~404 (1998)
- Pharoah PD, "Survival in familial, BRCA1-associated, and BRCA2-associated epithelial ovarian cancer. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group", Cancer Res, 59, pp.868~871 (1999)
- Lim MC, "BRCA1 and BRCA2 germline mutations in Korean ovarian cancer patients", J Cancer Res Clin Oncol, 135, pp.1593~1599 (2009)
- Kim YT, "Germline mutations of BRCA1 and BRCA2 in Korean sporadic ovarian carcinoma", Gynecol Oncol, 99, pp.585~590 (2005)
- Choi MC, "Germline mutations of BRCA1 and BRCA2 in Korean ovarian cancer patients : finding founder mutations", Int J Gynecol Cancer, 25, pp.1386~1391 (2015)
- 강은영, "The Korean Hereditary Breast Cancer Study: Review and Future Perspectives", Journal of Breast Cancer, 16(3), pp.245~253 (2013), 한국유방암학회
- Aida H, "Clinical features of ovarian cancer in Japanese women with germ-line mutations of BRCA1", Clin Cancer Res, 4, pp.235~240 (1998)
- Calo V, "The clinical significance of unknown sequence variants in BRCA genes", Cancers(Basel), 2, pp.1644~1660 (2010)
- Xu X, "Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoformdeficient cells", Mol Cell, 3, pp.389~395 (1999)
- Yang H, "BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure", Science, 297, pp.1837~1848 (2002)
- Gudmundsdottir K, "The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability", Oncogene, 25, pp.5864~5874 (2006)
- Muggia F, "'BRCAness' and its implications for platinum action in gynecologic cancer", Anticancer Res, 34, pp.551~556 (2014)
- Lord CJ, "BRCAness revisited", Nat Rev Cancer, 16, pp.110~120 (2016)
- Quinn JE, "BRCA1 mRNA expression levels predict for overall survival in ovarian cancer after chemotherapy", Clin Cancer Res, 13, pp.7413~7420 (2007)
- Frank TS, "Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2 : analysis of 10, 000individuals", J Clin Oncol, 20, pp.1480~1490 (2002)
- Easton DF, "A systematic genetic assessment of 1, 433sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes", Am J Hum Genet, 81, pp.873~883 (2007)
- Nanda R, "Genetic testing in an ethnically diverse cohort of high-risk women : a comparative analysis of BRCA1and BRCA2 mutations in American families of European and African ancestry", JAMA, 294, pp.1925~1933 (2005)
- Weitzel JN, "Prevalence of BRCA mutations and founder effect in high-risk Hispanic families", Cancer Epidemiol Biomarkers Prev, 14, pp.1666~1671 (2005)
- Sekine M, "Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families : two common founder mutations of BRCA1 in Japanese population", Clin Cancer Res, 7, pp.3144~3150 (2001)
- Schlich-Bakker KJ, "Barriers to participating in genetic counseling and BRCA testing during primary treatment for breast cancer", Genet Med, 9, pp.766~777 (2007)
- Fong PC, "Inhibition of poly(ADP-ribose)polymerase in tumors from BRCA mutation carriers", N Engl J Med, 361, pp.123~134 (2009)