Clinicoepidemilogical Correlation of BRCA 1 and 2 Mutations in Carcinoma Ovary - an Indian Perspective

Abstract

Introduction: All over the world in 2008, approximately 225,000 women were diagnosed with ovarian cancer, and 140,000 died from this disease.[1] Ovarian cancer is the second-most common gynecologic malignancy in the developed countries. In the developing countries, it is the third-most common gynecologic malignancy after breast and cervical cancer with an incidence of 5.0/100,000 and a mortality rate of 3.1/100,000. Women with BRCA1 gene mutations typically develop ovarian cancer at an earlier age than other women, with an average age at diagnosis of 50-year-old while for patients with BRCA2 mutation carriers it is 60 years, similar to the general population. Aim and Objective: The aim of this study is to study the incidence, clinical profile, and outcomes of a patient with BRCA 1 and BRCA 2 mutation in carcinoma ovary and its comparison with patients without mutation. Results: Out of total 50 patients, 45 (90%) were BRCA negative and rest fi ve (10%) were BRCA positive. Of the five patients, only two (4% of total) had pathological mutations while the rest of three patients had benign mutations only. Overall median age of presentation was 61 years for BRCA-negative patients and 38 years for BRCA-positive patients. Most of the patients presented in Stage III (23 out of 50; 46%), while the second-most common presentation was in Stage IV (34%). In our study, we had an overall mortality of one patient who was BRCA negative, in Stage IV while no mortality was noted in BRCA positive subset of patients. Conclusion: This was a single center-based and spanned over 24 months involving limited number of patients with ovarian cancer with maximum follow-up for 9 months.

Keywords

BRCA 1 and 2 mutations - carcinoma ovary - germline mutation

Publication History

Received: 25 March 2018

Accepted: 21 June 2018

Article published online:
03 June 2021

• References

• 1 Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. et al. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90
• 2 Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9-29
• 3 Available from: http://www.seer.cancer.gov/statfacts/html/ovary.html. [Last accessed on 2012 Apr 24]
• 4 Lacey JV, Sherman ME. Ovarian neoplasia. In: Robboy SL, Mutter GL, Prat J. editors Robboy’s Pathology of the Female Reproductive Tract. 2nd ed. Oxford: Churchill Livingstone Elsevier; 2009: 601
• 5 Berek JS, Crum C, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet 2012; 119 (02) Suppl S118-29
• 6 King MC, Marks JH, Mandell JB. New York Breast Cancer Study Group. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003; 302: 643-6
• 7 Satagopan JM, Boyd J, Kauff ND, Robson M, Scheuer L, Narod S. et al. Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Clin Cancer Res 2002; 8: 3776-81
• 8 Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007; 25: 1329-33
• 9 Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H. et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer 2005; 104: 2807-16
• 10 Bolton KL, Chenevix-Trench G, Goh C, Sadetzki S, Ramus SJ, Karlan BY. et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA 2012; 307: 382-90
• 11 Taniguchi T, Tischkowitz M, Ameziane N, Hodgson SV, Mathew CG, Joenje H. et al. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med 2003; 9: 568-74
• 12 Cass I, Baldwin RL, Varkey T, Moslehi R, Narod SA, Karlan BY. et al. Improved survival in women with BRCA-associated ovarian carcinoma. Cancer 2003; 97: 2187-95
• 13 Tan DS, Rothermundt C, Thomas K, Bancroft E, Eeles R, Shanley S. et al. “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 2008; 26: 5530-6
• 14 Levine DA, Argenta PA, Yee CJ, Marshall DS, Olvera N, Bogomolniy F. et al. Fallopian tube and primary peritoneal carcinomas associated with BRCA mutations. J Clin Oncol 2003; 21: 4222-7
• 15 Aziz S, Kuperstein G, Rosen B, Cole D, Nedelcu R, McLaughlin J. et al. A genetic epidemiological study of carcinoma of the fallopian tube. Gynecol Oncol 2001; 80: 341-5
• 16 Cass I, Holschneider C, Datta N, Barbuto D, Walts AE, Karlan BY. et al. BRCA-mutation-associated fallopian tube carcinoma: A distinct clinical phenotype?. Obstet Gynecol 2005; 106: 1327-34
• 17 Pennington KP, Swisher EM. Hereditary ovarian cancer: Beyond the usual suspects. Gynecol Oncol 2012; 124: 347-53
• 18 Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Anglian Breast Cancer Study Group. Br J Cancer 2000; 83: 1301-8
• 19 Indian Council of Medical Research. Consolidated Report of Population Based Cancer Registries 2012-2014. Bangalore: Indian Council of Medical Research; 2014
• 20 Boyd J, Sonoda Y, Federici MG, Bogomolniy F, Rhei E, Maresco DL. et al. Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 2000; 283: 2260-5
• 21 Lakhani SR, Manek S, Penault-Llorca F, Flanagan A, Arnout L, Merrett S. et al. Pathology of ovarian cancers in BRCA1 and BRCA2 carriers. Clin Cancer Res 2004; 10: 2473-81
• 22 Piver MS. Hereditary ovarian cancer. Lessons from the first twenty years of the Gilda Radner familial ovarian cancer registry. Gynecol Oncol 2002; 85: 9-17
• 23 Saini SK, Srivastava S, Singh Y. Epidemiology of epithelial ovarian cancer, a single institution-based study in India. Clini Cancer Investig J 2016; 5: 20-4