BRCA 1 and 2 somatic mutation in high grade serous epithelial ovarian cancer in Indonesian women that was operated on Dr. Soetomo General Hospital, Surabaya in 2019-2021

Jonathan Kevin Djuanda; Brahmana Askandar Tjokroprawiro; Grace Ariani

doi:10.15562/bmj.v12i2.4504

BRCA 1 and 2 somatic mutation in high grade serous epithelial ovarian cancer in Indonesian women that was operated on Dr. Soetomo General Hospital, Surabaya in 2019-2021

Jonathan Kevin Djuanda ,

Brahmana Askandar Tjokroprawiro ,

Grace Ariani ,

pdf |
DOI: https://doi.org/10.15562/bmj.v12i2.4504 |
Published: 2023-05-23

Abstract

Link of Video Abstract: https://youtu.be/9kem7M9SNWI

Background: Ovarian cancer remains as major problem worldwide. BRCA1 and BRCA2 play a unique role in deoxyribonucleic acid (DNA) damage repair, especially in homologous recombination repair. There are no data on the prevalence of BRCA1 and BRCA2 somatic mutations in the Indonesian population. This study aimed to determine the incidence of BRCA1 and BRCA2 somatic mutations among a cohort of patients with high-grade serous epithelial ovarian cancer, and assess its correlation with clinical characteristics of the cohort.

Methods: This was an analytical observational study of 26 patients admitted to our hospital from 2019 to 2021. Pathological specimens were obtained from the patients and examined for BRCA1 and BRCA2 somatic mutations. Data on clinical characteristics were collected from medical records. Statistical analysis was performed to determine the relationship between BRCA mutation status and clinical characteristics, including age, stage, menopausal status, parity, family history of malignancy, and patient outcomes.

Results: Twenty-six patients with high-grade serous epithelial ovarian cancer were included in the study. Six patients (27% of 22 patients) had BRCA1 and BRCA2 somatic mutations, four did not pass the quality control test, and the remaining tested negative for these mutations. Most patients were over 50 years of age (73%). Additionally, 84% of patients were diagnosed at stage III, and only one patient had a family history of malignancy. At the end of the study, most patients (65%) had died. Statistical analysis showed no significant differences between the clinical characteristics of the groups.

Conclusion: The incidence of BRCA1 and BRCA2 somatic mutations among patients with high-grade serous epithelial ovarian cancer at our hospital during 2019–2021 was 27%. There were no significant differences in the clinical characteristics of those with and without mutations, hence NGS screening following diagnosis establishment may be beneficial in further management plans.

References

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.
Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317:2402-2416.
Turashvili G, Lazaro C, Ying S, Charames G, Wong A, Hamilton K, et al. Tumor BRCA testing in high grade serous carcinoma: mutation rates and optimal tissue requirements. Cancers. 2020;12(11):3468.
Sullivan MR, Bernstein KA. Rad-iCal new insights into rad51 regulation. Genes (Basel). 2018;9(12):629.
Moschetta M, George A, Kaye SB, Banerjee S. BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Ann Oncol. 2016;27:1449-1455.
Konstantinopoulos PA, Norquist B, Lacchetti C, Armstrong D, Grisham RN, Goodfellow PJ, et al. Germline and somatic tumor testing in epithelial ovarian cancer: ASCO guideline. J Clin Oncol. 2020;38:1222-1245.
Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381:2416-2428.
Eoh KJ, Kim HM, Lee JY, Kim S, Kim SW, Kim YT, et al. Mutation landscape of germline and somatic BRCA1/2 in patients with high-grade serous ovarian cancer. BMC Cancer. 2020;20:204.
Kim SI, Lee M, Kim HS, Chung HH, Kim JW, Park NH, et al. Effect of BRCA mutational status on survival outcome in advanced-stage high-grade serous ovarian cancer. J Ovarian Res. 2019;12:40.
Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379:2495-2505.
Lin WT, Beattie M, Chen LM, Oktay K, Crawford SL, Gold EB, et al. Comparison of age at natural menopause in BRCA1/2mutation carriers with a non-clinic-based sample of women in northern california. Cancer. 2013;119:1652-1659.
Oktay K, Kim JY, Barad D, Babayev SN. Association of BRCA1 mutations with occult primary ovarian insufficiency: A possible explanation for the link between infertility and breast/ovarian cancer risks. J Clin Oncol. 2010;28:240-244.
Levanon K, Ng V, Piao HY, Zhang Y, Chang MC, Roh MH, et al. Primary ex vivo cultures of human fallopian tube epithelium as a model for serous ovarian carcinogenesis. Oncogene. 2010;29:1103-1113.
Milne RL, Osorio A, Ramón y Cajal T, Baiget M, Lasa A, Diaz-Rubio E, et al. Parity and the risk of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2010;119:221-232.
Clavel-Chapelon F, E3N-EPIC Group. Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women. Br J Cancer. 2002;86:723-727.
Paik ES, Heo EJ, Choi CH, Kim JH, Kim JW, Kim YM, et al. Prevalence and clinical characterization of BRCA1 and BRCA2 mutations in Korean patients with epithelial ovarian cancer. Cancer Sci. 2021;112:5055-5067.
Shi T, Wang P, Tang W, Jiang R, Yin S, Shi D, et al. Survival benefit of germline BRCA mutation is associated with residual disease in ovarian cancer. Cell Physiol Biochem. 2018;47:2088-2096.
Prakosa T, Mudigdo A, Purwanto B, Wasita B, Cilmiaty R, Widianingsih V. A cross-sectional study: The correlation of pro-angiogenic factors expression level and epithelial ovarian cancer staging. Bali Med J. 2020;9(1):125-128.
Prabowo A, Tjokroprawiro BA, Utomo B. Correlation between clinicopathological factors and clinical outcomes of recurrent epithelial ovarian cancer at a tertiary hospital in Surabaya, Indonesia. Bali Med J. 2022;11(2):807-812.
Dewi IGASM, Susraini AAAN, Ekawati NP. HER2/neu and Ki-67 as prognostic factors in serous type ovarian carcinoma. Bali Med J. 2020;9(2):567-571.
Gori S, Barberis M, Bella MA, Buttitta F, Capoluongo E, Carrera P, et al. Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives. Crit Rev Oncol Hematol. 2019;140:67-72.