Molecular-biological characteristics of triple negative breast cancer
https://doi.org/10.17650/1726-9784-2018-17-1-23-27
Abstract
Breast cancer is the most common disease in women all over the world. In the structure of cancer morbidity, breast cancer ranks first and its frequency is steadily increasing. In the world, about 1.67 million new cases are diagnosed and every year more than 500,000 women die from breast cancer. Triple negative breast cancer (TNBC) is about 15–20 % of all breast tumors; is more common in women of fertile age. TNBC is characterized by a lack of expression of estrogen, progesterone receptors and HER-2/neu, which significantly complicates the treatment of this disease, which is characterized by aggressive course, the maximum risk of recurrence during the first 3 yearsafter surgical treatment, and rapid metastasis and decreased life expectancy. This article presents a review of the literature on the molecular-biological characteristics of TNBC. The article also describes the main approaches to targeted therapies for each subtype.
About the Authors
N. E. Atakhanova
Tashkent Medical Academy
Uzbekistan
2 Pharobi St., Tashkent 100169
Uzbekistan
2 Pharobi St., Tashkent 100169
D. M. Almuradova
Tashkent Medical Academy
Uzbekistan
2 Pharobi St., Tashkent 100169
Uzbekistan
2 Pharobi St., Tashkent 100169
I A. Dudina
Sechenov University
Russian Federation
Bldg. 2, 8 Trubetskaya St., Moscow 119991
Russian Federation
Bldg. 2, 8 Trubetskaya St., Moscow 119991
References
1. Dawood S., Broglio K., Kau S.W. et al. Triple receptornegative breast cancer: the effect of race on response to primary systemic treatment and survival outcomes. J Clin Oncol 2009;27(2):220–6. DOI: 10.1200/JCO.2008.17.9952. PMID: 19047281.
2. Irvin W.J. Jr., Carey L.A. What is triple-negative breast cancer? Eur J Cancer 2008;44(18):2799–805. DOI: 10.1016/j.ejca.2008.09.034. PMID: 19008097.
3. Lund M.J., Trivers K.F., Porter P.L. et al. Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res Treat 2009;113(2):357–70. DOI: 10.1007/s10549-008-9926-3. PMID: 18324472.
4. Bauer K.R., Brown M., Cress R.D. et al. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 2007;109(9): 1721–8. DOI: 10.1002/cncr.22618. PMID: 17387718.
5. Anders C., Carey L.A. Understanding and treating triple-negative breast cancer. Oncology 2008;22(11):1233–9. PMID: 18980022.
6. Dent R., Trudeau M., Pritchard K.I. et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007; 13(15 Pt 1):4429–34. DOI: 10.1158/1078-0432.CCR-06-3045. PMID: 17671126.
7. Hines S.L., Vallow L.A., Tan W.W. et al. 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. PMID: 18534964.
8. Lehmann B.D., Bauer J.A., Chen X. et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011;121(7):2750–67. DOI: 10.1172/JCI45014. PMID: 21633166.
9. Foulkes W.D., Stefansson I.M., Chappuis P.O. et al. Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 2003;95(19):1482–5. PMID: 14519755.
10. Lakhani S.R., Reis-Filho J.S., Fulford L. et al. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 2005;11(14):5175–80. DOI: 10.1158/1078-0432.CCR-04-2424. PMID: 16033833.
11. Yam C., Mani S.A., Moulder S.L. Targeting the molecular subtypes of triple negative breast cancer: Understanding the diversity to progress the field. Oncologist 2017;22(9):1086–93. DOI: 10.1634/theoncologist.2017-0095. PMID: 28559413.
12. Masuda H., Baggerly K.A., Wang Y. et al. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res 2013;19(19):5533–40. DOI: 10.1158/1078-0432.CCR-13-0799. PMID: 23948975.
13. Von Minckwitz G., Schneeweiss A., Loibl S. et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 2014;15(7):747–56. DOI: 10.1016/S1470-2045(14)70160-3. PMID: 24794243.
14. Von Minckwitz G., Hahnen E., Fasching P.A. et al. Pathological complete response (pCR) rates after carboplatin-containing neoadjuvant chemotherapy in patients with germline BRCA (gBRCA) mutation and triple-negative breast cancer (TNBC): Results from GeparSixto. J Clin Oncol 2014; 32(15 Suppl):1005. DOI: 10.1200/jco.2014.32.15_suppl.1005.
15. Fong P.C., Boss D.S., Yap T.A. et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 2009;361(2):123–34. DOI: 10.1056/NEJMoa0900212. PMID: 19553641.
16. Tutt A., Robson M., Garber J.E. et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 2010;376(9737):235–44. DOI: 10.1016/S0140-6736(10) 60892-6. PMID: 20609467.
17. O’Shaughnessy J., Schwartzberg L.S., Danso M.A. et al. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). J Clin Oncol 2011;29(15 Suppl):1007. DOI: 10.1200/jco.2011.29.15_suppl.1007.
18. Mateo J., Ong M., Tan D.S.P. et al. Appraising iniparib, the PARP inhibitor that never was – what must we learn? Nat Rev Clin Oncol 2013;10(12):688–96. DOI: 10.1038/nrclinonc.2013.177. PMID: 24129347.
19. Shen Y., Rehman F.L., Feng Y. et al. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin Cancer Res 2013;19(18):5003–15. DOI: 10.1158/1078-0432.CCR-13-1391. PMID: 23881923.
20. Rugo H.S., Olopade O., DeMichele A. et al. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016;375(1):23–34. DOI: 10.1056/NEJMoa1513749. PMID: 27406347.
21. Ziltsova E.K., Ivanova O.A., Krivorotko P.V. et al. Can the androgen receptor blocking become the basis of a new method of treatment of triple negative breast cancer? Malignant Tumours 2017;1:18–25. DOI: 10.18027/2224-5057-2017-1-18-25.
22. Lehmann B.D., Pietenpol J.A. Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes. J Pathol 2014;232(2):142–50. DOI: 10.1002/path.4280. PMID: 24114677.
23. Du F.L., Eckhardt B.L., Lim B. et al. Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype? Oncotarget 2015;6(15):12890–908. DOI: 10.18632/oncotarget.3849. PMID: 25973541.
24. Gibson G.R., Qian D., Ku J.K., Lai L.L. Metaplastic breast cancer: clinical features and outcomes. Am Surg 2005;71(9):725–30. PMID: 16468506.
25. Hennessy B.T., Giordano S., Broglio K. et al. Biphasic metaplastic sarcomatoid carcinoma of the breast. Ann Oncol 2006;17(4):605–13. DOI: 10.1093/annonc/mdl006. PMID: 16469754.
26. Jung S.Y., Kim H.Y., Nam B.H. et al. Worse prognosis of metaplastic breast cancer patients than other patients with triple-negative breast cancer. Breast Cancer Res Treat 2010;120(3):627–37. DOI: 10.1007/s10549-010-0780-8. PMID: 20143153.
27. Luini A., Aguilar M., Gatti G. et al. Metaplastic carcinoma of the breast, an unusual disease with worse prognosis: The experience of the European Institute of Oncology and review of the literature. Breast Cancer Res Treat 2007;101(3):349–53. DOI: 10.1007/s10549-006-9301-1. PMID: 17009109.
28. Rayson D., Adjei A.A., Suman V.J. et al. Metaplastic breast cancer: Prognosis and response to systemic therapy. Ann Oncol 1999;10(4):413–9. PMID: 10370783.
29. Basho R.K., Gilcrease M., Murthy R.K. et al. Targeting the PI3K/AKT/mTOR pathway for the treatment of mesenchymal triple-negative breast cancer: Evidence from a phase 1 trial of mTOR inhibition in combination with liposomal doxorubicin and bevacizumab. JAMA Oncol 2017;3(4):509–15. DOI: 10.1001/jamaoncol.2016.5281. PMID: 27893038.
30. Locatelli M.A., Aftimos P., Dees E.C. et al. Phase I study of the gamma secretase inhibitor PF-03084014 in combination with docetaxel in patients with advanced triple-negative breast cancer. Oncotarget 2017;8(2):2320–8. DOI: 10.18632/oncotarget.13727. PMID: 27906684.
31. Diéras V., Campone M., Yardley D.A. et al. Randomized, phase II, placebo-controlled trial of onartuzumab and/or bevacizumab in combination with weekly paclitaxel in patients with metastatic triple-negative breast cancer. Ann Oncol 2015;26(9):1904–10. DOI: 10.1093/annonc/mdv263. PMID: 26202594.
32. Shipitsin M., Campbell L.L., Argani P. et al. Molecular definition of breast tumor heterogeneity. Cancer Cell 2007;11(3):259–73. DOI: 10.1016/j.ccr.2007.01.013. PMID: 17349583.
33. Oettle H., Hilbig A., Seufferlein T. et al. Trabedersen (AP 12009) in the treatment of patients with advanced tumors: Completion of dose-escalation and first efficacy data. J Clin Oncol 2010; 28(15 Suppl): 2611. DOI: 10.1200/jco.2010.28.15_suppl. 2611.
34. Gonzalez-Angulo A.M., Stemke-Hale K., Palla S.L. et al. Androgen receptor levels and association with PIK3CA mutations and prognosis in breast cancer. Clin Cancer Res 2009;15(7):2472–8. DOI: 10.1158/1078-0432.CCR-08-1763. PMID: 19276248.
35. Park S., Koo J., Park H.S. et al. Expression of androgen receptors in primary breast cancer. Ann Oncol 2010;21(3):488–92. DOI: 10.1093/annonc/mdp510. PMID: 19887463.
36. McNamara K.M., Yoda T., Takagi K. et al. Androgen receptor in triple negative breast cancer. J Steroid Biochem Mol Biol 2013;133:66–76. DOI: 10.1016/j.jsbmb.2012.08.007. PMID: 22982153.
37. Рябчиков Д.А., Воротников И.К., Козлов Н.А., Чхиквадзе Н.В. Андрогеновые рецепторы как фактор прогноза в различных молекулярно-биологических подтипах рака молочной железы. Сибирский онкологический журнал 2017;16(3):40–5. DOI: 10.21294/1814-4861-2017-16-3-40-45.
38. Tate C.R., Rhodes L.V., Segar H.C. et al. Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res 2012;14(3):R79. DOI: 10.1186/bcr3192. PMID: 22613095.
39. Sabnis G.J., Goloubeva O., Chumsri S. et al. Functional activation of the estrogen receptor-α and aromatase by the HDAC inhibitor entinostat sensitizes ER-negative tumors to letrozole. Cancer Res 2011;71(5):1893–903. DOI: 10.1158/0008-5472.CAN-10-2458. PMID: 21245100.
40. Gucalp A., Tolaney S., Isakoff S.J. et al. Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clin Cancer Res 2013;19(19):5505–12. DOI: 10.1158/1078-0432.CCR-12-3327. PMID: 23965901.
41. Overmoyer B., Sanz-Altamira P., Taylor R.P. et al. Enobosarm: a targeted therapy for metastatic, androgen receptor positive, breast cancer. J Clin Oncol 2014;32(15 Suppl):568. DOI: 10.1200/jco.2014.32.15_suppl.568.
Review
For citations:
Atakhanova N.E., Almuradova D.M., Dudina I.A. Molecular-biological characteristics of triple negative breast cancer. Russian Journal of Biotherapy. 2018;17(1):23-27. (In Russ.) https://doi.org/10.17650/1726-9784-2018-17-1-23-27
Views:
391
Email this article 
