ORIGINAL ARTICLE
Clinicopathological characteristics and BRCA1/BRCA2 pathogenic variants of patients with breast cancer
1
Department of Medical Genetics, Faculty of Medicine, Mersin University, Mersin, Turkey
2
Department of Pathology, Faculty of Medicine, Mersin University, Mersin, Turkey
3
Vocational School of Health Service, Mersin University, Mersin, Turkey
Submission date: 2023-09-07
Final revision date: 2023-11-16
Acceptance date: 2023-12-03
Publication date: 2024-02-26
Corresponding author
Nazan Eras
Nazan Eras Department of Medical Genetics Mersin University Hospital Çiftlikköy Campus, Yenişehir, Mersin, 33343, Turkey
Nazan Eras Department of Medical Genetics Mersin University Hospital Çiftlikköy Campus, Yenişehir, Mersin, 33343, Turkey
Pol J Pathol 2024;75(1):1-7
KEYWORDS
TOPICS
ABSTRACT
Although BRCA genes are well-known breast cancer genes, the clinicopathological features of breast cancer patients carrying BRCA1/2 pathogenic variants have not been adequately defined. The goals of this study were to determine the distribution of BRCA1/2 variants in the Turkish population and its correlation with clinicopathological features.
Clinical data of 151 women who underwent BRCA1/2 gene testing at Mersin University Medical Faculty Hospital between 2016 and 2019 were retrospectively analyzed. BRCA1/2 variants were detected as pathogenic (n = 11), variants of uncertain significance (n = 5), likely benign (n = 3), and benign (n = 81) in breast cancer cases.
The BRCA1/2 pathogenic variant carriers had a higher histological grade, rate of triple- negative type, Ki-67 proliferation index, and rate of no special type carcinoma than the group without mutation (p = 0.03, 0.01, 0.04, and 0.02 respectively).
We analyzed the distribution of variants we detected in women living in our region and found that pathogenic variants in patients with breast cancer were associated with high histological grade, triple-negative type, high Ki-67 proliferation index, and histological type. Studies in diverse populations are needed to establish a clinicopathological relationship with variants more easily.
Clinical data of 151 women who underwent BRCA1/2 gene testing at Mersin University Medical Faculty Hospital between 2016 and 2019 were retrospectively analyzed. BRCA1/2 variants were detected as pathogenic (n = 11), variants of uncertain significance (n = 5), likely benign (n = 3), and benign (n = 81) in breast cancer cases.
The BRCA1/2 pathogenic variant carriers had a higher histological grade, rate of triple- negative type, Ki-67 proliferation index, and rate of no special type carcinoma than the group without mutation (p = 0.03, 0.01, 0.04, and 0.02 respectively).
We analyzed the distribution of variants we detected in women living in our region and found that pathogenic variants in patients with breast cancer were associated with high histological grade, triple-negative type, high Ki-67 proliferation index, and histological type. Studies in diverse populations are needed to establish a clinicopathological relationship with variants more easily.
REFERENCES (36)
1.
Mehiret G, Molla A, Tesfaw A. Knowledge on risk factors and practice of early detection methods of breast cancer among graduating students of Debre Tabor University, Northcentral Ethiopia. BMC Womens Health 2022; 22: 183.
2.
Thorat MA, Balasubramanian R. Breast cancer prevention in high-risk women. Best Pract Res Clin Obstet Gynaecol 2020; 65: 18-31.
3.
Yit LFN, Ng CT, Wong FY, et al. Modern-era radiotherapy and ischaemic heart disease-related mortality outcomes in Asian breast-cancer patients. Contemp Oncol (Pozn) 2022; 26: 59-68.
4.
Liu H, Shi S, Gao J, et al. Analysis of risk factors associated with breast cancer in women: a systematic review and meta- analysis. Transl Cancer Res 2022; 11: 1344-1353.
5.
Youn HJ, Han W. A Review of the epidemiology of breast cancer in asia: focus on risk factors. Asian Pac J Cancer Prev 2020; 21: 867-880.
6.
Poorolajal J, Heidarimoghis F, Karami M, et al. Factors for the primary prevention of breast cancer: a meta-analysis of prospective cohort studies. J Res Health Sci 2021; 21: e00520.
7.
Pintican RM, Chiorean A, Duma M, et al. Are mutation carrier patients different from non-carrier patients? Genetic, pathology, and US features of patients with breast cancer. Cancers (Basel) 2022; 14: 2759.
8.
Fararjeh A, Kaddumi E, Al-Khader A, Aburayyan W. The significance of StAR-related lipid transfer protein-3 expression in breast cancer. Pol J Pathol 2022; 73: 215-222.
9.
Sadeghi F, Asgari M, Matloubi M, et al. Molecular contribution of BRCA1 and BRCA2 to genome instability in breast cancer patients: review of radiosensitivity assays. Biol Proced Online 2020; 22: 23.
10.
Wooster R, Neuhausen SL, Mangion J, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 1994; 265: 2088-2090.
11.
Tavtigian SV, Simard J, Rommens J, et al. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet 1996; 12: 333-337.
12.
Winters S, Martin C, Murphy D, et al. Breast cancer epidemiology, prevention, and screening. Prog Mol Biol Transl Sci 2017; 151: 1-32.
13.
Lee A, Moon BI, Kim TH. BRCA1/BRCA2 pathogenic variant breast cancer: treatment and prevention strategies. Ann Lab Med 2020; 40: 114-121.
14.
Burguin A, Diorio C, Durocher F. Breast cancer treatments: updates and new challenges. J Pers Med 2021; 11: 808.
15.
Hartmann LC, Schaid DJ, Woods JE, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999; 340: 77-84.
16.
Kaas R, Verhoef S, Wesseling J, et al. Prophylactic mastectomy in BRCA1 and BRCA2 mutation carriers. Ann Surg 2010; 251: 488-492.
17.
Kauff ND, Domchek SM, Friebel TM, et al. Risk reducing salpingo-oophorectomy for the prevention of BRCA1 and BRCA2 associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol 2008; 26: 1331-1337.
18.
Fanale D, Fiorino A, Incorvaia L, et al. Prevalence and spectrum of germline BRCA1 and BRCA2 variants of uncertain significance in breast/ovarian cancer: mysterious signals from the genome. Front Oncol 2021; 11: 682445.
19.
Agalliu I, Gern R, Leanza S, et al. Associations of high-grade prostate cancer with BRCA1 and BRCA2 founder mutations. Clin Cancer Res 2009; 15: 1112-1120.
20.
Di Lorenzo S, Fanale D, Corradino B, et al. Absence of germline CDKN2A mutation in Sicilian patients with familial malignant melanoma: could it be a population-specific genetic signature? Cancer Biol Ther 2016; 17: 83-90.
21.
Hu C, Hart SN, Polley EC, et al. Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer. JAMA 2018; 319: 2401-2409.
22.
Federici G, Soddu S. Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers. J Exp Clin Cancer Res 2020; 39: 46.
24.
Geredeli C, Yasar N, Sakin A. Germline mutations in BRCA1 and BRCA2 in breast cancer patients with high genetic risk in Turkish population. Int J Breast Cancer 2019; 2019: 9645147.
25.
Cecener G, Sabour Takanlou L, Sabour Takanlou M, et al. Clinicopathologic features and genetic characteristics of the BRCA1/2 mutation in Turkish breast cancer patients. Cancer Genet 2020; 240: 23-32.
26.
Bisgin A, Sag SO, Dogan ME, et al. Germline landscape of BRCAs by 7-site collaborations as a BRCA consortium in Turkey. Breast 2022; 65: 15-22.
27.
Yildiz Tacar S, Bozgeyik E, Seber ES, et al. Next generation sequencing analysis of BRCA1 and BRCA2 identifies novel variations in breast cancer. Life Sci 2020; 261: 118334.
28.
Fountzilas E, Konstantopoulou I, Vagena A, et al. Pathology of BRCA1- and BRCA2-associated breast cancers: known and less known connections. Clin Breast Cancer 2020; 20: 152-159.
29.
Atci MM, Geredeli Ç, Ay S, et al. Clinical and pathological characteristics of patients with high-risk breast cancer based on BRCA mutation profiles: a retrospective study. Eur J Breast Health 2021; 17: 123-127.
30.
Bayraktar S, Amendola L, Gutierrez-Barrera AM, et al. Clinicopathologic characteristics of breast cancer in BRCA-carriers and non-carriers in women 35 years of age or less. Breast 2014; 23: 770-774.
31.
Paik HJ, Jung YJ, Kim DI, et al. Clinicopathological features of BRCA1/2 mutation-positive breast cancer. Oncology 2021; 99: 499-506.
32.
You C, Xiao Q, Zhu X, et al. The clinicopathological and MRI features of patients with BRCA1/2 mutations in familial breast cancer. Gland Surg 2021; 10: 262-272.
33.
Eras N, Daloglu FT, Çolak T, et al. The correlation between IL-1-C31T gene polymorphism and susceptibility to breast cancer. J Breast Cancer 2019; 22: 210-218.
34.
Rijnsburger AJ, Obdeijn IM, Kaas R, et al. BRCA1-associated breast cancers present differently from BRCA2-associated and familial cases: long-term follow-up of the Dutch MRISC Screening Study. J Clin Oncol 2010; 28: 5265-5273.
35.
Louis DM, Nair LM, Vallonthaiel AG, et al. Ki 67: a promising prognostic marker in early breast cancer-a review article. Indian J Surg Oncol 2023; 14: 122-127.
36.
Calvo V, Beato M. BRCA1 counteracts progesterone action by ubiquitination leading to progesterone receptor degradation and epigenetic silencing of target promoters. Cancer Res 2011; 71: 3422-3431.
Share
RELATED ARTICLE
| eISSN: | 2084-9869 |
| ISSN: | 1233-9687 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
