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Contribution of BRCA1 5382insC mutation to triplene-gative and luminal types of breast cancer in Ukraine

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Abstract

Purpose

The gene BRCA1 plays a key role in DNA repair in breast and ovarian cell lines and this is considered one of target tumor suppressor genes in same line of cancers. The 5382insC mutation is among the most frequently detected in patients (Eastern Europe) with triple-negative breast cancer (TNBC). In Ukraine, there is not enough awareness of necessity to test patients with TNBC for BRCA1 mutations. That is why this group of patients is not well-studied, even through is known the mutation may affect the course of disease.

Methods

The biological samples of 408 female patients were analyzed of the 5382insC mutation in BRCA1. We compared the frequency of the 5382insC mutation in BRCA1 gene observed in Ukraine with known frequencies in other countries.

Results

For patients with TNBC, BRCA1 mutations frequency was 11.3%, while in patients with luminal types of breast cancers, the frequency was 2.8%. Prevalence of 5382insC among TNBC patients reported in this study was not different from those in Tunisia, Poland, Russia, and Bulgaria, but was higher than in Australia and Germany.

Conclusion

The BRCA1 c.5382 mutation rate was recorded for the first time for TNBC patients in a Ukrainian population. The results presented in this study underscore the importance of this genetic testing of mutations in patients with TNBC. Our study supports BRCA1/2 genetic testing for all women diagnosed with TNBC, regardless of the age of onset or family history of cancer and not only for women diagnosed with TNBC at <60y.o., as guidelines recommend.

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Data availability

The datasets generated during and analyed during the current study are not publicly available due to principles of ethics and medical confidentiality but are available from the corresponding author on reasonable request.

References

  1. CANCER IN UKRAINE 2019–2020 - Bulletin of the National Cancer Registry of Ukraine Vol.22. Accessed 9 Nov 2021 http://www.ncru.inf.ua/publications/BULL_22/index_e.htm.

  2. Rosen EM, Fan S, Pestell RG, Goldberg ID (2003) BRCA1 gene in breast cancer. J Cell Physiol 196:19–41. https://doi.org/10.1002/jcp.10257

    Article  CAS  PubMed  Google Scholar 

  3. Hashizume R, Fukuda M, Maeda I et al (2001) The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation. J Biol Chem 276:14537–14540. https://doi.org/10.1074/jbc.C000881200

    Article  CAS  PubMed  Google Scholar 

  4. Silver DP, Livingston DM (2012) Mechanisms of BRCA1 tumor suppression. Cancer Discov 2:679–684. https://doi.org/10.1158/2159-8290.CD-12-0221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gorodetska I, Kozeretska I, Dubrovska A (2019) BRCA genes: the role in genome stability, cancer stemness and therapy resistance. J Cancer 10:2109–2127. https://doi.org/10.7150/jca.30410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sy SMH, Huen MSY, Chen J (2009) PALB2 is an integral component of the BRCA complex required for homologous recombination repair. Proc Natl Acad Sci U S A 106:7155–7160. https://doi.org/10.1073/pnas.0811159106

    Article  PubMed  PubMed Central  Google Scholar 

  7. Clark SL, Rodriguez AM, Snyder RR et al (2012) Structure-function of the tumor suppressor BRCA1. Comput Struct Biotechnol J 1:e201204005. https://doi.org/10.5936/csbj.201204005

    Article  PubMed  PubMed Central  Google Scholar 

  8. Laitman Y, Feng B-J, Zamir IM et al (2013) Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations. Eur J Hum Genet 21:212–216. https://doi.org/10.1038/ejhg.2012.124

    Article  CAS  PubMed  Google Scholar 

  9. Gayther SA, Warren W, Mazoyer S et al (1995) Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation. Nat Genet 11:428–433. https://doi.org/10.1038/ng1295-428

    Article  CAS  PubMed  Google Scholar 

  10. Prevalence of two BRCA1 mutations, 5382insC and 300T > G, in ovarian cancer patients from Ukraine - PubMed. Accessed 8 Nov 2021 https://pubmed.ncbi.nlm.nih.gov/28285342/.

  11. Sokolenko AP, Mitiushkina NV, Buslov KG et al (2006) High frequency of BRCA1 5382insC mutation in Russian breast cancer patients. Eur J Cancer 42:1380–1384. https://doi.org/10.1016/j.ejca.2006.01.050

    Article  CAS  PubMed  Google Scholar 

  12. Savanevich A, Oszurek O, Lubiński J et al (2014) BRCA1 founder mutations compared to ovarian cancer in Belarus. Fam Cancer 13:445–447. https://doi.org/10.1007/s10689-014-9721-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kroupis C, Christopoulos K, Devetzoglou M et al (2008) Asymmetric real-time PCR detection of BRCA1 5382insC mutation by melting curve analysis in the lightcycler. Clin Chim Acta 390:141–144. https://doi.org/10.1016/j.cca.2007.12.024

    Article  CAS  PubMed  Google Scholar 

  14. The frequency of BRCA1 founder mutation c.5266dupC (5382insC) in breast cancer patients from Ukraine | Hereditary Cancer in Clinical Practice | Full Text. Accessed 8 Nov 2021 https://hccpjournal.biomedcentral.com/articles/https://doi.org/10.1186/s13053-015-0040-3.

  15. Vona-Davis L, Rose DP, Hazard H et al (2008) Triple-negative breast cancer and obesity in a rural appalachian population. Cancer Epidemiol Biomarkers Prev 17:3319–3324. https://doi.org/10.1158/1055-9965.EPI-08-0544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Perou CM, Sørlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752. https://doi.org/10.1038/35021093

    Article  CAS  PubMed  Google Scholar 

  17. Carey LA, Perou CM, Livasy CA et al (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295:2492–2502. https://doi.org/10.1001/jama.295.21.2492

    Article  CAS  PubMed  Google Scholar 

  18. Gene-Panel Sequencing and the Prediction of Breast-Cancer Risk | NEJM. Accessed 8 Nov 2021 https://www.nejm.org/doi/full/10.1056/nejmsr1501341.

  19. Robertson L, Hanson H, Seal S et al (2012) BRCA1 testing should be offered to individuals with triple-negative breast cancer diagnosed below 50 years. Br J Cancer 106:1234–1238. https://doi.org/10.1038/bjc.2012.31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Atchley DP, Albarracin CT, Lopez A et al (2008) Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer. J Clin Oncol 26:4282–4288. https://doi.org/10.1200/JCO.2008.16.6231

    Article  PubMed  PubMed Central  Google Scholar 

  21. van den Broek AJ, Schmidt MK, van ‘t Veer LJ, et al (2015) Worse Breast cancer prognosis of BRCA1/BRCA2 mutation Carriers: what’s the evidence? a systematic review with meta-analysis. PLoS ONE 10:e0120189. https://doi.org/10.1371/journal.pone.0120189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Maksimenko J, Irmejs A, Nakazawa-Miklasevica M et al (2014) Prognostic role of BRCA1 mutation in patients with triple-negative breast cancer. Oncol Lett 7:278–284. https://doi.org/10.3892/ol.2013.1684

    Article  CAS  PubMed  Google Scholar 

  23. Copson ER, Maishman TC, Tapper WJ et al (2018) Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol 19:169–180. https://doi.org/10.1016/S1470-2045(17)30891-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Joosse SA, Brandwijk KIM, Mulder L et al (2011) Genomic signature of BRCA1 deficiency in sporadic basal-like breast tumors. Genes Chromosomes Cancer 50:71–81. https://doi.org/10.1002/gcc.20833

    Article  CAS  PubMed  Google Scholar 

  25. Watanabe Y, Maeda I, Oikawa R et al (2013) Aberrant DNA methylation status of DNA repair genes in breast cancer treated with neoadjuvant chemotherapy. Genes Cells 18:1120–1130. https://doi.org/10.1111/gtc.12100

    Article  CAS  PubMed  Google Scholar 

  26. Armstrong N, Ryder S, Forbes C et al (2019) A systematic review of the international prevalence of BRCA mutation in breast cancer. Clin Epidemiol 11:543–561. https://doi.org/10.2147/CLEP.S206949

    Article  PubMed  PubMed Central  Google Scholar 

  27. Couch FJ, Hart SN, Sharma P et al (2015) Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol 33:304–311. https://doi.org/10.1200/JCO.2014.57.1414

    Article  CAS  PubMed  Google Scholar 

  28. Hahnen E, Lederer B, Hauke J et al (2017) Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer: secondary analysis of the geparsixto randomized clinical trial. JAMA Oncol 3:1378–1385. https://doi.org/10.1001/jamaoncol.2017.1007

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mahfoudh W, Bettaieb I, Ghedira R et al (2019) Contribution of BRCA1 5382insC mutation in triple negative breast cancer in Tunisia. J Transl Med 17:123. https://doi.org/10.1186/s12967-019-1873-8

    Article  PubMed  PubMed Central  Google Scholar 

  30. Pogoda K, Niwińska A, Sarnowska E et al (2020) Effects of BRCA germline mutations on triple-negative breast cancer prognosis. J Oncol 2020:8545643. https://doi.org/10.1155/2020/8545643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wong-Brown MW, Meldrum CJ, Carpenter JE et al (2015) Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. Breast Cancer Res Treat 150:71–80. https://doi.org/10.1007/s10549-015-3293-7

    Article  CAS  PubMed  Google Scholar 

  32. Gordeeva L, Lojko I, Voronina E et al (2018) Mutations in tumor suppressor genes and their relationship with phenotypic features of breast cancer in young age women. Ecolo genet 16(3):62–71. https://doi.org/10.17816/ecogen16362-71

    Article  Google Scholar 

  33. Kovacheva KS, Kamburova ZB, Popovska SL et al (2018) Prevalence of Five BRCA1/2 Mutations in Bulgarian Breast Cancer Patients. J Biomed Clin Res 11:123–127. https://doi.org/10.2478/jbcr-2018-0017

    Article  Google Scholar 

  34. Ryu JM, Choi HJ, Kim I et al (2019) Prevalence and oncologic outcomes of BRCA 1/2 mutations in unselected triple-negative breast cancer patients in Korea. Breast Cancer Res Treat 173:385–395. https://doi.org/10.1007/s10549-018-5015-4

    Article  CAS  PubMed  Google Scholar 

  35. Bertucci F, Finetti P, Cervera N et al (2008) How basal are triple-negative breast cancers? Int J Cancer 123:236–240. https://doi.org/10.1002/ijc.23518

    Article  CAS  PubMed  Google Scholar 

  36. Zhang L, Yang A, Wang M et al (2016) Enhanced autophagy reveals vulnerability of P-gp mediated epirubicin resistance in triple negative breast cancer cells. Apoptosis 21:473–488. https://doi.org/10.1007/s10495-016-1214-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bosviel R, Garcia S, Lavediaux G et al (2012) BRCA1 promoter methylation in peripheral blood DNA was identified in sporadic breast cancer and controls. Cancer Epidemiol 36:e177-182. https://doi.org/10.1016/j.canep.2012.02.001

    Article  CAS  PubMed  Google Scholar 

  38. Vos S, Moelans CB, van Diest PJ (2017) BRCA promoter methylation in sporadic versus BRCA germline mutation-related breast cancers. Breast Cancer Res 19:64. https://doi.org/10.1186/s13058-017-0856-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lobanova OE, Rossokha ZI, Medvedieva NL et al (2021) Prevalence of BRCA1 and BRCA2 genes promoter hypermethylation in breast cancer tissue. Exp Oncol 43(1):56–60. https://doi.org/10.32471/exp-oncology.2312-8852

    Article  CAS  PubMed  Google Scholar 

  40. Tabano S, Azzollini J, Pesenti C et al (2020) Analysis of BRCA1 and RAD51C promoter methylation in italian families at high-risk of breast and ovarian cancer. Cancers (Basel) 12:E910. https://doi.org/10.3390/cancers12040910

    Article  CAS  Google Scholar 

  41. Chen H, Wu J, Zhang Z et al (2018) Association between BRCA status and triple-negative breast cancer: a meta-analysis. Front Pharmacol 9:909. https://doi.org/10.3389/fphar.2018.00909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Peshkin BN, Alabek ML, Isaacs C (2010) BRCA1/2 mutations and triple negative breast cancERS. Breast Dis. https://doi.org/10.3233/BD-2010-0306.10.3233/BD-2010-0306

    Article  PubMed  PubMed Central  Google Scholar 

  43. Huszno J, Kołosza Z, Grzybowska E (2019) BRCA1 mutation in breast cancer patients: analysis of prognostic factors and survival. Oncol Lett 17:1986–1995. https://doi.org/10.3892/ol.2018.9770

    Article  CAS  PubMed  Google Scholar 

  44. Incorvaia L, Fanale D, Bono M et al (2020) BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients. Ther Adv Med Oncol 12:1758835920975326. https://doi.org/10.1177/1758835920975326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Koboldt DC, Fulton RS, McLellan MD et al (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70. https://doi.org/10.1038/nature11412

    Article  CAS  Google Scholar 

  46. Fujisawa F, Tamaki Y, Inoue T et al (2021) Prevalence of BRCA1 and BRCA2 mutations in Japanese patients with triple-negative breast cancer: a single institute retrospective study. Mol Clin Oncol 14:96. https://doi.org/10.3892/mco.2021.2258

    Article  PubMed  PubMed Central  Google Scholar 

  47. Rummel S, Varner E, Shriver CD, Ellsworth RE (2013) Evaluation of BRCA1 mutations in an unselected patient population with triple-negative breast cancer. Breast Cancer Res Treat 137:119–125. https://doi.org/10.1007/s10549-012-2348-2

    Article  PubMed  Google Scholar 

  48. González-Rivera M, Lobo M, López-Tarruella S et al (2016) Frequency of germline DNA genetic findings in an unselected prospective cohort of triple-negative breast cancer patients participating in a platinum-based neoadjuvant chemotherapy trial. Breast Cancer Res Treat 156:507–515. https://doi.org/10.1007/s10549-016-3792-1

    Article  CAS  PubMed  Google Scholar 

  49. Palomba G, Budroni M, Olmeo N et al (2014) Triple-negative breast cancer frequency and type of BRCA mutation: clues from Sardinia. Oncol Lett 7:948–952. https://doi.org/10.3892/ol.2014.1834

    Article  PubMed  PubMed Central  Google Scholar 

  50. Hamameh SL, Renbaum P, Kamal L et al (2017) Genomic analysis of inherited breast cancer among palestinian women: Genetic heterogeneity and a founder mutation in TP53. Int J Cancer 141:750–756. https://doi.org/10.1002/ijc.30771

    Article  CAS  PubMed Central  Google Scholar 

  51. Lebert JM, Lester R, Powell E et al (2018) Advances in the systemic treatment of triple-negative breast cancer. Curr Oncol 25:S142–S150. https://doi.org/10.3747/co.25.3954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bayraktar S, Gutierrez-Barrera AM, Liu D et al (2011) Outcome of triple-negative breast cancer in patients with or without deleterious BRCA mutations. Breast Cancer Res Treat 130:145–153. https://doi.org/10.1007/s10549-011-1711-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Lyons TG (2019) Targeted therapies for triple-negative breast cancer. Curr Treat Options Oncol 20:82. https://doi.org/10.1007/s11864-019-0682-x

    Article  PubMed  Google Scholar 

  54. Robson ME, Tung N, Conte P et al (2019) OlympiAD final overall survival and tolerability results: olaparib versus chemotherapy treatment of physician’s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol 30:558–566. https://doi.org/10.1093/annonc/mdz012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Litton JK, Hurvitz SA, Mina LA et al (2020) Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol 31:1526–1535. https://doi.org/10.1016/j.annonc.2020.08.2098

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We appreciate the helpful comments provided by two anonymous reviewers. The authors thank Prof Timothy Mousseau (University of South Carolina, SC) for his useful comments and English proofreading and all brave defenders of Ukraine that made finalizing this work possible.

Funding

Authors declare no conflict of interest in funding of this research. Svitlana Serga is supported by PAUSE Program (Solidarity with Ukraine).

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Authors and Affiliations

  1. Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine

    Anastasiia Samusieva, Sergiy Klymenko, Natalia Gorovenko, Nataliia Levkovich & Olga Ponomarova

  2. Taras Shevchenko National University of Kyiv, Kyiv, Ukraine

    Svitlana Serga & Iryna Kozeretska

  3. Bogomolets National Medical University, Kyiv, Ukraine

    Sergiy Klymenko, Liubov Zakhartseva, Olga Lobanova & Valeriy Cheshuk

  4. State Institution National Research Center for Radiation Medicine of NAMS of Ukraine, Kyiv, Ukraine

    Lyudmila Rybchenko

  5. Feofaniya Clinical Hospital, Kyiv, Ukraine

    Bohdana Klimuk

  6. Kyiv Municipal Clinical Oncological Center, Kyiv, Ukraine

    Liubov Zakhartseva & Olga Ponomarova

  7. State Institution Reference-Center for Molecular Diagnostics of Public Health Ministry of Ukraine, Kyiv, Ukraine

    Zoia Rossokha, Liliia Fishchuk, Nataliia Medvedieva & Olena Popova

  8. National Cancer Institute, Kyiv, Ukraine

    Mariia Inomistova, Natalia Khranovska, Oksana Skachkova & Yurii Michailovich

Authors
  1. Anastasiia Samusieva
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  2. Svitlana Serga
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  3. Sergiy Klymenko
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  4. Lyudmila Rybchenko
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  6. Liubov Zakhartseva
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  7. Natalia Gorovenko
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  8. Olga Lobanova
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  9. Zoia Rossokha
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  10. Liliia Fishchuk
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  11. Nataliia Levkovich
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  18. Yurii Michailovich
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Contributions

AS: Conceptualization, Methodology, Writing—Original Draft, Preparation, Writing—Review & Editing. SS: Conceptualization, Methodology, Investigation, Writing—Original Draft, Preparation, Writing—Review & Editing. ZR, SK: Methodology, Investigation, Data Curation, Review &Editing. LR, BK, LZ, NG, OL, LF, NL, NM, OP, VC, MI, NK, OS, YM: Methodology, Investigation. OP, IK: Conceptualization, Writing—Original Draft, Preparation, Writing—Review & Editing, Supervision, Project Administration. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Anastasiia Samusieva.

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The authors declare that they have no conflict of interest.

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This study was performed in line with the principles of the Declaration of Helsinki and approved by the local ethics committee (Committee on Bioethics: Bogomolets National Medical University, Kyiv (# 0120U100871).

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Informed consent was obtained from all individual participants included in the study.

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Samusieva, A., Serga, S., Klymenko, S. et al. Contribution of BRCA1 5382insC mutation to triplene-gative and luminal types of breast cancer in Ukraine. Breast Cancer Res Treat 195, 453–459 (2022). https://doi.org/10.1007/s10549-022-06692-3

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