Triple Negative Breast Cancer: Molecular Classification, Prognostic Markers and Targeted Therapies

Jafarzadeh, Narges; Ashraf, Hami; Khoshroo, Fahimeh; Sepehri Shamloo, Alireza; Bidouei, Farzad; Ghaffarzadehgan, Kamran

doi:10.30483/rijm.2015.118321

Triple Negative Breast Cancer: Molecular Classification, Prognostic Markers and Targeted Therapies

Authors

¹ Department of Research and Education, Razavi Hospital, Mashhad, IR Iran

² Student Research Committee, Mashhad University of Medical Sciences, Mashhad, IR Iran

10.30483/rijm.2015.118321

Abstract

Background: Triple negative breast cancer (TNBC) is a heterogeneous group of diseases that is negative for esterogen receptor (ER) progesteron receptor (PR) and human epidermal growth factor receptor 2 (HER2). This type of breast cancer is typically high-grade carcinomas, although low-grade tumors occur. The aim of this review is to focus on molecular classification and features, prognostic markers and targeted therapies of triple negative breast cancer.

Evidence Acquisition: We searched using electronic databases Pubmed/Medline, Dare, Scopus, Embase, and Cochrane Database of Systematic Reviews with terms of ‘Triple negative breast cancer’, ‘Breast cancer’, ‘Molecular classification’, ‘Immunohistochemical markers’, ‘Molecular features, ‘Targeted therapy’, and ‘Prognostic marker’.

Results: It seems that TNBC itself can be subdivided into immunomodulatory, mesenchymal, mesenchymal stem-like, luminal androgen receptor, and distinct basal-like subtypes that differ substantially from basal-like tumors. There are several prognostic makers for TNBC including EGFR and ALDH1, Lysyl Oxidase-Like 2 protein (LOXL2), Synuclein gamma (SNCG), LDHB (Lactate Dehydrogenase B). The antiangiogenic agents, EGFR inhibitors, and PARP inhibitors are new therapeutic Implications and potent factors to targeted therapies of TNBC.

Conclusions: Only a few clinical trials are performed on TNBC patients because this disease has a low incidence. Therefore, it seems larger scale clinical trials are needed to be conducted in the future.

Keywords

Open Access Policy: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/

References

1. Redig AJ, McAllister SS. Breast cancer as a systemic disease: a view of metastasis. J Intern Med. 2013;274(2):113-26. https://doi.org/10.1111/joim.12084 PMid:23844915 PMCid:PMC3711134

2. Rakha EA, Reis-Filho JS, Baehner F, Dabbs DJ, Decker T, Eusebi V, et al. Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res. 2010;12(4):207. 3. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006;295(21):2492-502. https://doi.org/10.1001/jama.295.21.2492 PMid:16757721

3. Oakman C, Viale G, Di Leo A. Management of triple negative breast cancer. Breast. 2010;19(5):312-21. https://doi.org/10.1016/j.breast.2010.03.026 PMid:20382530

4. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429-34. https://doi.org/10.1158/1078-0432.CCR-06-3045 PMid:17671126

5. Perou CM. Molecular stratification of triple-negative breast cancers. Oncologist. 2010;15 Suppl 5:39-48. https://doi.org/10.1634/theoncologist.2010-S5-39 PMid:21138954

6. Dawood S. Triple-negative breast cancer: epidemiology and management options. Drugs. 2010;70(17):2247-58. https://doi.org/10.2165/11538150-000000000-00000 PMid:21080741

7. Lara-Medina F, Perez-Sanchez V, Saavedra-Perez D, Blake-Cerda M, Arce C, Motola-Kuba D, et al. Triple-negative breast cancer in Hispanic patients: high prevalence, poor prognosis, and association with menopausal status, body mass index, and parity. Cancer. 2011;117(16):3658-69. https://doi.org/10.1002/cncr.25961 PMid:21387260

8. Brady-West DC, McGrowder DA. Triple negative breast cancer: therapeutic and prognostic implications. Asian Pac J Cancer Prev. 2011;12(8):2139-43.

9. Dolle JM, Daling JR, White E, Brinton LA, Doody DR, Porter PL, et al. Risk factors for triple-negative breast cancer in women under the age of 45 years. Cancer Epidemiol Biomarkers Prev. 2009;18(4):1157-66. https://doi.org/10.1158/1055-9965.EPI-08-1005 PMid:19336554 PMCid:PMC2754710

10. Bosch A, Eroles P, Zaragoza R, Vina JR, Lluch A. Triple-negative breast cancer: molecular features, pathogenesis, treatment and current lines of research. Cancer Treat Rev. 2010;36(3):206-15. https://doi.org/10.1016/j.ctrv.2009.12.002 PMid:20060649

11. Carey L, Winer E, Viale G, Cameron D, Gianni L. Triple-negative breast cancer: disease entity or title of convenience? Nat Rev Clin Oncol. 2010;7(12):683-92. https://doi.org/10.1038/nrclinonc.2010.154 PMid:20877296

12. Rodriguez-Pinilla SM, Sarrio D, Honrado E, Hardisson D, Calero F, Benitez J, et al. Prognostic significance of basal-like phenotype and fascin expression in node-negative invasive breast carcinomas. Clin Cancer Res. 2006;12(5):1533-9. https://doi.org/10.1158/1078-0432.CCR-05-2281 PMid:16533778

13. Foulkes WD, Stefansson IM, Chappuis PO, Begin LR, Goffin JR, Wong N, et al. Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst. 2003;95(19):1482-5. 15. Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 2010;12(5):R68. https://doi.org/10.1186/bcr2635 PMid:20813035 PMCid:PMC3096954

14. Turner N, Lambros MB, Horlings HM, Pearson A, Sharpe R, Natrajan R, et al. Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets. Oncogene. 2010;29(14):2013-23. https://doi.org/10.1038/onc.2009.489 PMid:20101236 PMCid:PMC2852518

15. Andre F, Job B, Dessen P, Tordai A, Michiels S, Liedtke C, et al. Molecular characterization of breast cancer with high-resolution oligonucleotide comparative genomic hybridization array. Clin Cancer Res. 2009;15(2):441-51. https://doi.org/10.1158/1078-0432.CCR-08-1791 PMid:19147748

16. Rody A, Karn T, Liedtke C, Pusztai L, Ruckhaeberle E, Hanker L, et al. A clinically relevant gen