Vol 17, No 1 (2021)
Research paper
Published online: 2020-07-10
Page views 678
Article views/downloads 676
Get Citation

Connect on Social Media

Connect on Social Media

The study of genetic and clinicopathological characterisation of Turkish bilateral breast cancer patients

Neslihan Duzkale1, Hikmet Taner Teker2
Oncol Clin Pract 2021;17(1):6-13.

Abstract

Introduction. Although bilateral breast cancers are a rare condition in the general population, the incidence has increased significantly in BRCA1 and BRCA2 gene carrier breast cancer patients. Besides the genetic susceptibility, many risk factors such as age, first breast cancer diagnosis age, lifestyle, and environmental factors may be effective in the development of this type of cancer. This study aimed to determine BRCA1/2 gene carriage in patients with bilateral breast cancer and to find out the risk factors that may lead to contralateral cancer formation. 

Material and methods. From 2016 to 2018, in Turkey, we grouped 31 women diagnosed with bilateral breast cancer synchronously and metasynchronously. Analysis of BRCA1 and BRCA2 genes of these women evaluated for clinical and pathological tumour characteristics was performed using the NGS technique. 

Results. No significant difference was found between the metachronous (MBBC) and synchronous (SBBC) groups in terms of clinical and pathological tumour characteristics. MBBC patients’ age at first diagnosis of breast cancer was lower than SBBC. Also, there was a statistically significant relationship between chronic diseases and MBBC cancers (c2 = 11.519; p = 0.001). In our study, disease-related variants were found only in three patients, and two of these variants were identified the first time in the literature. 

Conclusion. The risk of bilateral breast cancer of BRCA1/2 carriers increases when the first breast cancer is diagnosed at a young age and there is a significant family history of cancer. MBBC is associated with chronic diseases, and large-scale research will contribute to clarifying this relationship.

Article available in PDF format

Purchase Subscription

References

  1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394–424.
  2. Soerjomataram I, Louwman WJ, de Vries E, et al. Primary malignancy after primary female breast cancer in the South of the Netherlands, 1972–2001. Breast Cancer Res Treat. 2005; 93(1): 91–95.
  3. Intra M, Rotmensz N, Viale G, et al. Clinicopathologic characteristics of 143 patients with synchronous bilateral invasive breast carcinomas treated in a single institution. Cancer. 2004; 101(5): 905–912.
  4. Cook LS, White E, Schwartz SM, et al. A population-based study of contralateral breast cancer following a first primary breast cancer (Washington, United States). Cancer Causes Control. 1996; 7(3): 382–390.
  5. Lu W, Schaapveld M, Jansen L, et al. The value of surveillance mammography of the contralateral breast in patients with a history of breast cancer. Eur J Cancer. 2009; 45(17): 3000–3007.
  6. Metcalfe K, Gershman S, Lynch HT, et al. Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer. 2011; 104(9): 1384–1392.
  7. Hartman M, Czene K, Reilly M, et al. Incidence and prognosis of synchronous and metachronous bilateral breast cancer. J Clin Oncol. 2007; 25(27): 4210–4216.
  8. Hartman M, Czene K, Reilly M, et al. Genetic implications of bilateral breast cancer: a population based cohort study. Lancet Oncol. 2005; 6(6): 377–382.
  9. Kuo WH, Yen AMF, Lee PH, et al. Incidence and risk factors associated with bilateral breast cancer in area with early age diagnosis but low incidence of primary breast cancer: analysis of 10-year longitudinal cohort in Taiwan. Breast Cancer Res Treat. 2006; 99(2): 221–228.
  10. Jobsen JJ, van der Palen J, Ong F, et al. Bilateral breast cancer, synchronous and metachronous; differences and outcome. Breast Cancer Res Treat. 2015; 153(2): 277–283.
  11. Beck AC, Yuan H, Liao J, et al. Rate of BRCA mutation in patients tested under NCCN genetic testing criteria. Am J Surg. 2020; 219(1): 145–149.
  12. Ozturk A, Alco G, Sarsenov D, et al. Synchronous and metachronous bilateral breast cancer: A long-term experience. J BUON. 2018; 23(6): 1591–1600.
  13. Richards S, Aziz N, Bale S, et al. ACMG Laboratory Quality Assurance Committee. 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. 2015; 17(5): 405–424.
  14. de Garibay GR, Acedo A, García-Casado Z, et al. Capillary electrophoresis analysis of conventional splicing assays: IARC analytical and clinical classification of 31 BRCA2 genetic variants. Hum Mutat. 2014; 35(1): 53–57.
  15. Santos C, Peixoto A, Rocha P, et al. Pathogenicity evaluation of BRCA1 and BRCA2 unclassified variants identified in Portuguese breast/ovarian cancer families. J Mol Diagn. 2014; 16(3): 324–334.
  16. Tazzite A, Jouhadi H, Nadifi S, et al. BRCA1 and BRCA2 germline mutations in Moroccan breast/ovarian cancer families: novel mutations and unclassified variants. Gynecol Oncol. 2012; 125(3): 687–692.
  17. Tavtigian SV, Byrnes GB, Goldgar DE, et al. Classification of rare missense substitutions, using risk surfaces, with genetic- and molecular-epidemiology applications. Hum Mutat. 2008; 29(11): 1342–1354.
  18. De Silva S, Tennekoon KH, Karunanayake EH, et al. Novel sequence variants and common recurrent polymorphisms of BRCA2 in Sri Lankan breast cancer patients and a family with BRCA1 mutations. Exp Ther Med. 2011; 2(6): 1163–1170.
  19. Karbassi I, Maston GA, Love A, et al. A standardized DNA variant scoring system for pathogenicity assessments in mendelian disorders. Hum Mutat. 2016; 37(1): 127–134.
  20. Goetz MP, Gradishar WJ, Anderson BO, et al. NCCN Guidelines Insights: Breast Cancer, Version 3.2018. J Natl Compr Canc Netw. 2019; 17(2): 118–126.
  21. Warren S, Gates O. Multiple primary malignant tumors. Am J Cancer. 1932; 16: 1358.
  22. Narod SA. Bilateral breast cancers. Nat Rev Clin Oncol. 2014; 11(3): 157–166.
  23. Graeser MK, Engel C, Rhiem K, et al. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2009; 27(35): 5887–5892.
  24. Weitzel JN, Robson M, Pasini B, et al. A comparison of bilateral breast cancers in BRCA carriers. Cancer Epidemiol Biomarkers Prev. 2005; 14(6): 1534–1538.
  25. Rogozińska-Szczepka J, Utracka-Hutka B, Grzybowska E, et al. BRCA1 and BRCA2 mutations as prognostic factors in bilateral breast cancer patients. Ann Oncol. 2004; 15(9): 1373–1376.
  26. Sim Y, Tan VKM, Sidek NAB, et al. Bilateral breast cancers in an Asian population, and a comparison between synchronous and metachronous tumours. ANZ J Surg. 2018; 88(10): 982–987.