Results of immunohistochemistry diagnostics of breast cancer in the region of Grodno with consideration of the BRCA1 gene mutation in triple negative cancer

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Abstract

Background: The results of immunohistochemical (IHC) assessment in breast cancer may determine not only the outcome, but also the main directions of antitumor treatment.

Aim: To study the results of IHC diagnosis of breast cancer in the Grodno region in 2010 to 2015, to determine the frequency of the BRCA1 gene mutations in triple-negative breast cancer.

Materials and methods: 2008 cases of estrogen receptor and/or progesterone receptor positive and 2445 cases of HER2/neu expressing breast cancer were extracted from the database and IHC laboratory journals of the Grodno Regional Clinical Bureau for Pathological Anatomy. Standard DAKO kits (Denmark) were used for IHC. Molecular genetic studies of DNA samples for the presence of the BRCA genes mutations were done by polymerase chain reaction in 449 women with breast cancer. BRCA1 mutation was assessed in 39 cases of triple-negative breast cancer.

Results: HER2/neu overexpression (3+) was found in 25.5% (622/2445) of all breast cancer cases, whereas of estrogen receptor and progesterone receptor positive tumors in 50.05% (1105/2008) of cases. Triple negative breast cancer was diagnosed in 19.8% (398/2008) of cases, and the mean age of the patients at the diagnosis was 56.2 years. The BRCA1 gene mutations were identified in 5 of 39 (12.8%) cases of triple negative breast cancer, which is significantly more often than in women with breast cancer without consideration of their hereditary predisposition (17/449, or 3.8%; χ2 = 4.87, p = 0.0274). Histological examination showed that among the tumors with the BRCA1 mutations, there were 3 cases with invasive ductal cancer (one G2 and two G3), one with medullary and one with undifferentiated G3 cancer. One patient had a metachronous bilateral lesion.

Conclusion: In the region of Grodno, 50% of breast cancer patients would need hormonal therapy, 25% would need treatment with trastuzumab, and 20% with cytostatic agents. The prevalence of the BRCA1 mutation in triple negative breast cancer is higher compared to that in breast cancer patients without consideration of their hereditary predisposition.

About the authors

A. Yu. Krylov

Institute of Further Training and Retraining of the Personnel of the State Forensic Examination Committee of the Republic of Belarus

Author for correspondence.
Email: andrei_krilov@mail.ru

MD, PhD, Associate Professor, Head of the Chair of Forensic Medicine

60/7 Kizhevatova str., Minsk, 220024, Republic of Belarus. Tel.: +375 29 614 87 41

Белоруссия

M. G. Zubritsky

Grodno Regional Bureaus Mortem

Email: fake@neicon.ru

MD, PhD, Head Officer

52 Leninskogo Komsomola blvd, Grodno, 230030, Republic of Belarus

Белоруссия

I. A. Kurstak

Grodno State Medical University

Email: fake@neicon.ru

MD, PhD, Assistant, Chair of Clinical Laboratory Diagnostics, Allergology and Immunology

80 Gorkogo str., Grodno, 230009, Republic of Belarus

Белоруссия

S. A. Lialikau

Grodno State Medical University

Email: fake@neicon.ru

MD, PhD, Professor, Head of the Chair of Clinical Laboratory Diagnostics, Allergology and Immunology

80 Gorkogo str., Grodno, 230009, Republic of Belarus

Белоруссия

V. A. Basinski

Grodno State Medical University

Email: fake@neicon.ru

MD, PhD, Professor, Head of the Chair of Anatomical Pathology and Forensic Medicine

80 Gorkogo str., Grodno, 230009, Republic of Belarus

Белоруссия

References

  1. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ; Panel members. Strategies for subtypes – dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22(8): 1736–47. doi: 10.1093/annonc/mdr304.
  2. Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thürlimann B, Senn HJ; Panel Members. Tailoring therapies – improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 2015;26(8): 1533–46. doi: 10.1093/annonc/mdv221.
  3. Суконко ОГ, Красный СА, ред. Алгоритмы диагностики и лечения злокачественных новообразований. Минск: Профессиональные издания; 2012. 508 с.
  4. Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363(20): 1938–48. doi: 10.1056/NEJMra1001389.
  5. Podo F, Buydens LM, Degani H, Hilhorst R, Klipp E, Gribbestad IS, Van Huffel S, van Laarhoven HW, Luts J, Monleon D, Postma GJ, Schneiderhan-Marra N, Santoro F, Wouters H, Russnes HG, Sørlie T, Tagliabue E, Børresen- Dale AL; FEMME Consortium. Triple-negative breast cancer: present challenges and new perspectives. Mol Oncol. 2010;4(3): 209–29. doi: 10.1016/j.molonc.2010.04.006.
  6. Phipps AI, Buist DS, Malone KE, Barlow WE, Porter PL, Kerlikowske K, Li CI. Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk. Breast Cancer Res Treat. 2011;126(3): 671–8. doi: 10.1007/s10549-010-1148-9.
  7. Claus EB, Risch N, Thompson WD. Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet. 1991;48(2): 232–42.
  8. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal J, Hussey C, Tran T, McClure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Ward J, Tonin P, Narod S, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barrett JC, Lewis C, Neuhausen S, Albright L, Goldgar D, Wiseman R, Kamb A, Skolnick MH. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266(5182): 66–71.
  9. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378(6559): 789–92. doi: 10.1038/378789a0.
  10. Tun NM, Villani G, Ong K, Yoe L, Bo ZM. Risk of having BRCA1 mutation in high-risk women with triple-negative breast cancer: a meta- analysis. Clin Genet. 2014;85(1): 43–8. doi: 10.1111/cge.12270.
  11. Ягудина РИ, Куликов АЮ, Нгуен Т. Обзор зарубежных фармакоэкономических исследований применения герцептина при лечении рака молочной железы. Фармакоэкономика. Современная фармакоэкономика и фармакоэпидемиология. 2009;2(2): 28–35.
  12. Dent R, Hanna WM, Trudeau M, Rawlinson E, Sun P, Narod SA. Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat. 2009;115(2): 423–8. doi: 10.1007/s10549-008-0086-2.
  13. Nishimura R, Arima N. Is triple negative a prognostic factor in breast cancer? Breast Cancer. 2008;15(4): 303–8. doi: 10.1007/s12282-008-0042-3.
  14. Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, Perou CM, Nielsen TO. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008;14(5): 1368– 76. doi: 10.1158/1078-0432.CCR-07-1658.
  15. Hines SL, Vallow LA, Tan WW, McNeil RB, Perez EA, Jain A. Clinical outcomes after a diagnosis of brain metastases in patients with estrogen- and/or human epidermal growth factor receptor 2-positive versus triple-negative breast cancer. Ann Oncol. 2008;19(9): 1561–5. doi: 10.1093/annonc/mdn283.
  16. Panousis D, Ntasiou P, Grosomanidis D, Chatzopoulos K, Lagoudianakis E, Charitidou E, Xepapadakis G. Single centre clinical study of a Greek patient population with triple- negative breast cancer. Hellenic J Surg. 2014;86(5): 280–6. doi: 10.1007/s13126-014-0146-5.
  17. Keam B, Im SA, Kim HJ, Oh DY, Kim JH, Lee SH, Chie EK, Han W, Kim DW, Moon WK, Kim TY, Park IA, Noh DY, Heo DS, Ha SW, Bang YJ. Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer. BMC Cancer. 2007;7:203. doi: 10.1186/1471-2407-7-203.
  18. Bidard FC, Conforti R, Boulet T, Michiels S, Delaloge S, André F. Does triple-negative phenotype accurately identify basal-like tumour? An immunohistochemical analysis based on 143 'triple-negative' breast cancers. Ann Oncol. 2007;18(7): 1285–6. doi: 10.1093/annonc/mdm360.
  19. Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, van de Vijver MJ. Gene expression profiling and histopathological characterization of triple- negative/basal- like breast carcinomas. Breast Cancer Res. 2007;9(5):R65. doi: 10.1186/bcr1771.
  20. Battifora H. Assessment of antigen damage in immunohistochemistry. The vimentin internal control. Am J Clin Pathol. 1991;96(5): 669–71.
  21. Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007;8(3): 235–44. doi: 10.1016/S1470-2045(07)70074-8.
  22. Morris GJ, Naidu S, Topham AK, Guiles F, Xu Y, McCue P, Schwartz GF, Park PK, Rosenberg AL, Brill K, Mitchell EP. Differences in breast carcinoma characteristics in newly diagnosed African- American and Caucasian patients: a single- institution compilation compared with the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer. 2007;110(4): 876–84. doi: 10.1002/cncr.22836.
  23. Чиссов ВИ, Дарьялова СЛ, ред. Онкология: клинические рекомендации. 2-е изд., испр. и доп. М.: ГЭОТАР-Медиа; 2009. 928 с.
  24. Schmidt G, Meyberg-Solomayer G, Gerlinger C, Juhasz-Böss I, Herr D, Rody A, Liedtke C, Solomayer EF. Identification of prognostic different subgroups in triple negative breast cancer by Her2-neu protein expression. Arch Gynecol Obstet. 2014;290(6): 1221–9. doi: 10.1007/s00404-014-3331-4.
  25. Кузнецов ОЕ, Ляликов СА, Савицкий СЭ, Курстак ИА. Частота мутаций гена BRCA и клинический риск при наследственных опухолях женской репродуктивной системы. Здравоохранение (Минск). 2011;(4): 71–4.
  26. Курстак ИА, Ляликов СА, Кузнецов ОЕ, Ершова МВ. Прогностическая значимость клинико-генетических признаков в диагностике предрасположенности к наследственному раку молочной железы и яичников у здоровых лиц в белорусской популяции. Журнал Гродненского государственного медицинского университета. 2013;(1): 34–6.
  27. Курстак ИА, Ляликов СА, Кузнецов ОЕ, Ершова МВ. Прогнозирование мутации в генах BRCA у пациенток с раком молочной железы. Лабораторная диагностика. Восточная Европа. 2014;(1): 24–30.
  28. Крылов АЮ, Крылов ЮВ, Зубрицкий МГ, Курстак ИА, Ляликов СА, Басинский ВА. Клинико-морфологический анализ выявления BRCA1 с иммуногистохимической оценкой экспрессии рецепторов андрогенов и C-kit (CD117) при тройном негативном раке молочной железы у женщин Гродненской области. Проблемы здоровья и экологии. 2016;(4): 25–8.

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Copyright (c) 2017 Krylov A.Y., Zubritsky M.G., Kurstak I.A., Lialikau S.A., Basinski V.A.

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