A.M. ZHUMAKAEVA¹, E.I. ZHAPPAROV¹, N.A. SHANAZAROV², S.V. ZINCHENKO³, N.K. SEYDALIN², G.P. ARIPZHANOVA², A.F. KHALIRAKHMANOV³

 ¹Multiprofile Medical Center, Nur-Sultan

² Hospital of Medical Center of the Executive office of the Kazakhstan President, Nur-Sultan

³Kazan (Volga) Federal University, Kazan

 Contact details:

Khalirakhmanov A.F. — PhD (medicine), doctor of the Department of X-ray Surgical Diagnostic and Treatment Methods, Senior Lecturer of the Department of Surgery, Obstetrics and Gynecology

Address: 1a Chekhov St., Russian Federation, Kazan, 420043, tel.: +7-929-722-33-34, e-mail: ai.bolit@mail.ru

Breast cancer occupies a leading position worldwide in the structure of oncological diseases in terms of morbidity and mortality. The life expectancy of patients has increased significantly due to the development of modern treatment methods such as targeted therapy, hormone and immunotherapy. This kind of treatment became available as a result of studying the molecular genetic features of breast cancer and the emergence of new diagnostic methods for detecting molecular structures. Currently, breast cancer treatment protocols are periodically updated and changed according to the results of modern research and the emergence of a new spectrum of targeted drugs and new targets for the drugs. In this review, we summarized the achievements of modern medicine in the field of molecular genetics and the features of breast cancer pathogenesis, such as luminal types of breast cancer, androgen positive types of breast cancer, new features of Her2/neu and Ki-67 overexpression.

Key words: breast cancer, biological subtypes, estrogen and progesterone receptors, androgen receptors, Her2/neu, Ki-67, single nucleotide polymorphisms.

REFERENCES

1. World Health Organization (WHO), 2018, available at: https://www.who.int/ru
2. Zdorov’e naseleniya Respubliki Kazakhstan i deyatel’nost’ organizatsiy zdravookhraneniya v 2018 g.: stat. sbornik [Health of the population of the Republic of Kazakhstan and the activities of health care organizations in 2018: statistical collection], Astana, 2018, no. 1, pp. 328–334 (in Russ.).
3. Pisareva L.F., Boyarkina A.L., Odintsova I.N. Gormonozavisimye opukholi: Materialy IX Vserossiyskoy konferentsii onkologov [Hormone-dependent tumors: Materials of the IX All-Russian conference of oncologists]. Saint Petersburg, 2010. Pp. 69–72.
4. White A.J., O’Brien K.M., Niehoff N.M., Carroll R., Sandler D.P. Metallic air pollutants and breast cancer risk in a nationwide cohort study. Epidemiology, 2019, vol. 30, rr. 20–28.
5. Anderson K.N., Schwab R.B., Martinez M.E. Reproductive risk factors and breast cancer subtypes: a review of the literature. Breast. Cancer. Res. Treat, 2014, vol. 144, rr. 1–10.
6. Weiderpass E., Persson I.R. Oncological diseases in menopause: causes and methods of prevention. Voprosy onkologii, 2001, vol. 47, no. 2, pp. 139–147 (in Russ.).
7. Copson E., Eccles B., Maishman T., Gerty S., Stanton L., Cutress R.I. et al. Prospective observational study of breast cancer treatment outcomes for UK women aged 18–40 years at diagnosis: the POSH study. J Natl Cancer Inst, 2013, vol. 105, rr. 978–988.
8. Ercan C., Diest P.J. Mammary Development and Breast Cancer: The Role of Stem Cells. Curr Mol Med, 2011, vol. 11, rr. 270–285.
9. Stepina M.B., Frolova M.A. Breast cancer: the most important scientific developments and findings of recent years. Prakticheskaya onkologiya, 2011, vol. 12, no. 1, pp. 6–11 (in Russ.).
10. Cardoso F., Costa A., Norton L., Senkus E., Aapro M., Andre F. et al. ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2). Breast, 2014, vol. 35, rr. 489–502.
11. Jiang B.H., Liu L.Z. PI3K/PTEN signaling in angiogenesis and tumorigenesis. Adv Cancer Res, 2009, vol. 102, rr. 49–65.
12. Chiang S.P., Cabrera R.M., Segall J.E. Tumor cell intravasation. Am. J. Physiol. Cell Physiol, 2016, vol. 311, rr. 1–14.
13. Meek D.W. Regulation of the p53 response and its relationship to cancer. Biochem J,2015, vol. 469, pp. 325–346.
14. Harding C., Pompei F., Burmistrov D., Welch H.G., Abebe R., Wilson R. Breast Cancer Screening, Incidence, and Mortality Across US Counties. JAMA Intern Med, 2015, vol. 175, pp. 1483–1489.
15. Done S.J., Eskandarian S., Bull S., Redston M., Andrulis I.L. p53 missense mutations in microdissected high-grade ductal carcinoma in situ of the breast. J Natl Cancer Inst,2001, vol. 93, rr. 700–704.
16. Sorlie T., Perou C.M., Tibshirani R., Aas T., Geisler S., Johnsen H., Hastie T., Eisen M.B., et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA, 2001, vol. 98, rr. 10869–10874.
17. Cheang M.C., Chia S.K., Voduc D., Gao D., Leung S., Snider J., et al. Ki 67 index, HER-2 status, and prognosis of patients with luminal B breast cancer. Journal of the National Cancer Institute, 2009, vol. 101, pp. 736–750.
18. Odle T.G. Precision Medicine in Breast Cancer. Radiol Technol, 2017, vol. 88, rr. 401–421.
19. Perou C.M., Sorlie T., Eisen M.B., Rijn M., Jeffrey S.S. Molecular portraits of human breast tumors. Nature, 2000, vol. 406, pp. 747–752.
20. Arteaga C.L., et al. Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol, 2012, no. 9, pp. 16–32.
21. Hashmi A.A., Edhi M.M., Naqvi H., Khurshid A., Faridi N. Molecular subtypes of breast cancer in South Asian population by immunohistochemical profile and Her2neu gene amplification by FISH technique: association with other clinicopathologic parameters. Breast J., 2014, vol. 20 (6), pp. 578–585.
22. Cheang M.C., Chia S.K., Voduc D., Gao D., Leung S., Snider J., Watson M., Davies S., Bernard P.S., Parker J.S., Perou C.M., Ellis M.J., Nielsen T.O. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst, 2009, vol. 101 (10), pp. 736–750.
23. Blows F.M., Driver K.E., Schmidt M.K., Broeks A., Leeuwen F.E., Wesselling J. et al. Subtyping of breast cancer by immnohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLos Med, 2010, no. 7, R. 279.
24. Goldhirsch A., Wood W.C., Coates A.S. et al. 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, vol. 22, rr. 1736–1747.
25. Bauer K., Parise C., Caggiano V. Use of ER/PR/Her2 subtypes in conjunction with the 2007 St Gallen consensus statement for early breast cancer. BMC Cancer, 2010, no. 10, r. 228.
26. Vuong D., Simpson P.T., Green B., Cummings M.C., Lakhani S.R. Molecular classification of breast cancer. Virchows Arch, 2014, vol. 465, rr. 1–14.
27. Ivantsov A.O., Matsko D.E. Possibilities of immunohistochemical research in the diagnosis of tumors. Prakticheskaya onkologiya, 2011, vol. 12, no. 4, pp. 185–193 (in Russ.).
28. Amiroslanov A.T., Muradov Kh.K., Velieva A.G. Influence of the endocrine-cellular component on the course and prognosis of hormone-producing breast cancer. Rossiyskiy bioterapevticheskiy zhurnal, 2010, vol. 9, no. 4, pp. 51–54 (in Russ.).
29. Yoon E.C., Schwartz C., Brogi E., Ventura K., Wen H., Darvishian F. Impact of biomarkers and genetic profiling on breast cancer prognostication: A comparative analysis of the 8th edition of breast cancer staging system. Breast J, 2019, vol. 25, rr. 829–837.
30. Wolff A.C., Hammond M.E., Allison K.H., Harvey B.E., Mangu P.B., Bartlett J.M., Bilous M. et. al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology / College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol, 2018, vol. 36, rr. 2105–2122.
31. Rakha E.A, Pinder S.E., Bartlett J.M., Ibrahim M., Starczynski J., Carder P.J., Provenzano E. Updated UK Recommendations for HER2 assessment in breast cancer. J Clin Pathol, 2015, vol. 68, rr. 93–99.
32. Gershteyn E.S., Kushlinskiy N.E. Tkanevye markery kak faktory prognoza pri rake molochnoy zhelezy [Tissue markers as prognostic factors in breast cancer]. Prakticheskaya onkologiya. Saint Petersburg: Tsentr TOMM, 2004. Pp. 41–50.
33. Kuligina E.Sh. Epidemiological and molecular aspects of breast cancer. Prakticheskaya onkologiya, 2010, vol. 11, pp. 203–216 (in Russ.).
34. Nguyen T.H., Nguyen V.H., Nguyen T.L., Qiuyin C., Phung, T.H. Evaluations of Biomarker Status Changes between Primary and Recurrent Tumor Tissue Samples in Breast Cancer Patients. Bio Med Research International, 2019, vol. 23, rr. 1–7.
35. Yan M., Parker B.A, Schwab R., Kurzrock R. Her2 aberration in cancer: Implications for therapy. Cancer treat Rev, 2014, vol. 40, rr. 770–780.
36. Zeune L., van Dalsum G., Decraene C., Proudhon C., Fhm T., Neubauer H. et al. Quantifying HER-2 expression on circulating tumor cells by ACCEPT. PloS one, 2017, no. 12, rr. 1–12.
37. Riethdorf S., Muller V., Zhang L., Rau T., Loibl S., Komor M. et al. Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvantGeparQuattro trial. Clinical cancer research: an official journal of the American Association for Cancer Research, 2010, vol. 16, pp. 2634–2645.
38. Page K., Hava N., Ward B., Brown J., Guttery D.S., Ruangpratheep C. et al. Detection of HER2 amplification in circulating free DNA in patients with breast cancer. British journal of cancer, 2011, vol. 104, r. 1342.
39. McGranahan N., Swanton C. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer cell, 2015, no. 27 (1), rr. 15–26.
40. Engels C.C., Kiderlen M., Bastiaannet E., van Eijk R., Mooyaart A. The clinical value of HER-2 overexpression and PIK3CA mutations in the older breast cancer population: a FOCUS study analysis. Breast Cancer Res Treat, 2016, vol. 156, rr. 361–370.
41. Kono M., Fujii T., Lim B., Karuturi M.S., Tripathy D., Ueno N.T. Androgen Receptor Function and Androgen Receptor-Targeted Therapies in Breast Cancer: A Review. US National Library of Medicine National Institutes of Health JAMA Oncol, 2017, no. 3, rr. 1266–1273.
42. Pietri E., Conteduca V., Andreis D., Massa I., Melegari E., Sarti S., Cecconetto L. Androgen receptor signaling pathways as a target for breast cancer treatment. Endocr Relat Cancer, 2016, vol. 23, rr. 485–498.
43. Niemeier L.A., Dabbs D.J., Beriwal S. et al. Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation. Mod Pathol, 2010, vol. 23, rr. 205–212.
44. Tsang J.Y., Ni Y.B., Chan S.K. et al. Androgen receptor expression shows distinctive significance in ER positive and negative breast cancers. Ann Surg Oncol, 2014, vol. 21, rr. 2218–2228.
45. Bleach R., McIlroy M. The Divergent Function of Androgen Receptor in Breast Cancer; Analysis of Steroid Mediators and Tumor Intracrinology. Front Endocrinol (Lausanne), 2018, no. 9, rr. 594–607.
46. Zhang H., Sui X., Zhou S., Hu L., Huang X. Correlation of Conventional Ultrasound Characteristics of Breast Tumors With Axillary Lymph Node Metastasis and Ki-67 Expression in Patients With Breast Cancer. J Ultrasound Med, 2019, vol. 38, rr. 1833–1840.
47. Kim K.I., Lee K.H., Kim T.R., Chun Y.S., Lee T.H., Park H.K. Ki-67 as a predictor of response to neoadjuvant chemotherapy in breast cancer patients. J Breast Cancer, 2014, vol. 17, rr. 40–46.
48. Curtis C. et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature, 2012, vol. 46, rr. 346–352.
49. Poulakaki N., Makris G.M., Papanota A.M., Marineli F., Marinelis A., Battista M.J., Boehm D., Psyrri A., Sergentanis T.N. Ki-67 Expression as a Factor Predicting Recurrence of Ductal Carcinoma In Situ of the Breast: A Systematic Review and Meta-Analysis. Clin Breast Cancer, 2018, vol. 18, rr. 157–167.
50. Sadashima E., Hattori S., Takahashi K. Meta-analysis of prognostic studies for a biomarker with a study-specific cutoff value. Res Synth Methods, 2016, no. 7, rr. 402–419.
51. Luporsi E., Andre F., Spyratos F. Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review. Breast Cancer Res. Treat, 2012, vol. 132, pp. 895–915.
52. Chen X., He C., Han D., Zhou M., Wang Q., Tian J., Li L., Xu F., Zhou E., Yang K.. The predictive value of Ki-67 before neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis. Future Oncol, 2017, vol. 13, rr. 843–857.
53. Matsubara N., Mukai H., Fujii S., Wada N. Different prognostic significance of Ki-67 change between preand post-neoadjuvant chemotherapy in various subtypes of breast cancer. Breast Cancer Res. Treat, 2012, vol. 137, pp. 203–212.
54. Xu H., Eirew P., Mullaly S.C., Aparicio S. The omics of triplenegative breast cancers. Clin Chem, 2014, vol. 60, rr. 122–133.
55. Lehmann B.D., Bauer J.A., Chen X., Sanders M. E., Chakravarthy A.B., Shyr Y. et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 2011, vol. 12, rr. 2750–2767.
56. Horgan X.J., Tatum H., Brannan E., Paull D.H., Rhodes L.V. Resveratrol analogues surprisingly effective against triple‑negative breast cancer, independent of ERα. Oncol Rep, 2019, vol. 416, rr. 3517–3526.
57. Damaskos C., Garmpi A., Nikolettos K., Vavourakis M., Diamantis E., Patsouras A., Farmaki P. Triple-Negative Breast Cancer: The Progress of Targeted Therapies and Future Tendencies. Anticancer Res, 2019, vol. 39, rr. 5285–5296.
58. Lehmann B.D., Bauer J.A., Chen X., Sanders M.E., Chakravarthy A.B., Shyr Y. et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 2011, vol. 121, rr. 2750–2767.
59. Damaskos C., Garmpi A., Nikolettos K., Vavourakis M., Diamantis E., Patsouras A., Farmaki P., Nonni A. Triple-Negative Breast Cancer: The Progress of Targeted Therapies and Future Tendencies. Anticancer Res, 2019, vol. 39 (10), rr. 5285–5296.