The Role of the Molecular Subtypes in the Prognosis of Breast Cancer Patients

  • Stoyan Nikolov Department of Surgery, University Hospital “Prof. Dr Stoyan Kirkovich” Stara Zagora, Bulgaria
  • Emil Enchev Department of Surgery, University Hospital “Prof. Dr Stoyan Kirkovich” Stara Zagora, Bulgaria
  • Georgi Minkov Department of Surgery, University Hospital “Prof. Dr Stoyan Kirkovich” Stara Zagora, Bulgaria
  • Evgeni Dimitrov Department of Surgery, University Hospital “Prof. Dr Stoyan Kirkovich” Stara Zagora, Bulgaria
  • Koni Ivanova Department of Pathology, Faculty of Medicine, Trakia University Stara Zagora, Bulgaria
  • Maya Gulubova Department of Pathology, Faculty of Medicine, Trakia University Stara Zagora, Bulgaria
  • Tatyana Vlaykova Department of Biochemistry, Faculty of Medicine, Trakia University Stara Zagora, Bulgaria
  • Yovcho Yovtchev Department of Surgery, University Hospital “Prof. Dr Stoyan Kirkovich” Stara Zagora, Bulgaria
Keywords: breast cancer, molecular substypes, overall survival

Abstract

BACKGROUND: Understanding the biology of the tumor, by dividing it into molecular subtypes, has made it possible to individualize the therapeutic approach in high-risk patients.

AIM: We aimed to determine the importance of established molecular subtypes in the prognosis and the importance of disease-free and overall survival (OS) in patients with non-metastatic breast cancer.

MATERIALS AND METHODS: We analyzed 94 patients with non-metastatic breast cancer for the period 2010–2018. The median follow-up time was 60 months. The mean age in the study group was 60.03 years (SD ± 10.52). According to the characteristics of the studied indicators, we divided the group into Luminal A (n-59 [62.7%]), Luminal B/HER2 (−) (n-2 [2.1%]), Luminal B/HER2 (+) (n-8 [8.5%]), HER2 overexpressing (n-3 [3.2%]), and triple-negative subtype (n-22 [23.5%]). In all patients in the study group, we analyzed the 5-year overall survival (OS) and disease-free survival (DFS) and referred it to molecular subtypes, lymphatic status, HER-2 status, the presence or absence of endocrine therapy for the follow-up period, tumor differentiation, and type of surgery.

RESULTS: We observed the 5-year OS in 92% of patients identified as Luminal A; at 50% of Luminal B/HER2 (−) neg.; in 62.5% with Luminal B/HER2 (+), in 67% with HER2-overexpressing carcinoma; and in 66.7% of patients with triple-negative subtype. The total cancer-associated mortality rate in the analyzed period reached 15.9% (n = 15). Patients with mastectomy (p = 0.019, p = 0.027), positive axilla with more than 4 lymph node (LN) (p = 0.000; p = 0.000), and Luminal B/HER-2 (+) tumors (p = 0.004; p = 0.003) were the independent prognostic factors for worse DFS and OS in our study group. Histological differentiation and HER-2 expression were in unsatisfactory correlation (p = 0.077; p = 0.044 and p = 0.081; p = 0.055, respectively).

CONCLUSION: Molecular subtypes are essential in the prognosis of breast cancer and maybe a criterion for an individualized therapeutic approach.

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References

DeSantis C, Ma J, Bryan L, Jemal A. Breast cancer statistics, 2013. CA Cancer J Clin. 2014;64(1):52-62. https://doi. org/10.3322/caac.21203 PMid:24114568

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet. 2005;365(9472):1687-717. https:// doi.org/10.1016/s0140-6736(05)66544-0 PMid:15894097

Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-52. https://doi.org/10.1038/35021093 PMid:10963602

Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61- 70. https://doi.org/10.1038/nature11412 PMid:23000897

Ellis MJ, Perou CM. The genomic landscape of breast cancer as a therapeutic roadmap. Cancer Discov. 2013;3(1):27-34. PMid:23319768

Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol. 2011;5(1):5-23. PMid:21147047

Weigelt B, Baehner FL, Reis-Filho JS. The contribution of gene expression profiling to breast cancer classification, prognostication and prediction: A retrospective of the last decade. J Pathol. 2010;220(2):263-80. https://doi.org/10.1002/ path.2648 PMid:19927298

Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27(8):1160-7. https://doi. org/10.1200/jco.2008.18.1370 PMid:19204204

Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009;360(8):790-800. https://doi. org/10.1056/nejmra0801289 PMid:19228622

Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, 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;22(8):1736-47. https://doi.org/10.1093/ annonc/mdr304 PMid:21709140

Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart- Gebhart M, Thürlimann B, et al. Personalizing the treatment of women with early breast cancer: Highlights of the St gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol. 2013;24(9):2206-23. https://doi. org/10.1016/j.breast.2003.09.007 PMid:23917950

Hennigs A, Riedel F, Gondos A, Sinn P, Schirmacher P, Marmé F, et al. Prognosis of breast cancer molecular subtypes in routine clinical care: A large prospective cohort study. BMC Cancer. 2016;16(1):734. https://doi.org/10.1186/s12885-016-2766-3 PMid:27634735

Soerjomataram I, Lortet-Tieulent J, Parkin DM, Ferlay J, Mathers C, Forman D, et al. Global burden of cancer in 2008: A systematic analysis of disability-adjusted life-years in 12 world regions. Lancet. 2012;380(9856):1840-50. https://doi. org/10.1016/s0140-6736(12)60919-2 PMid:23079588

Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: Globocan 2008. Int J Cancer. 2010;127(12):2893-917. https://doi. org/10.1002/ijc.25516 PMid:21351269

Blows FM, Driver KE, Schmidt MK, Broeks A, van Leeuwen FE, Wesseling J, et al. Subtyping of breast cancer by immunohistochemistry 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;7(5):e1000279. https://doi.org/10.1371/journal. pmed.1000279 PMid:20520800

Williams C, Lin CY. Oestrogen receptors in breast cancer: Basic mechanisms and clinical implications. Ecancermedicalscience. 2013;7:370. PMid:24222786

Eroles P, Bosch A, Pérez-Fidalgo JA, Lluch A. Molecular biology in breast cancer: Intrinsic subtypes and signaling pathways. Cancer Treat Rev. 2012;38(6):698-707. https://doi. org/10.1016/j.ctrv.2011.11.005 PMid:22178455

Hashmi AA, Aijaz S, Khan SM, Mahboob R, Irfan M, Zafar NI, et al. Prognostic parameters of luminal A and luminal B intrinsic breast cancer subtypes of Pakistani patients. World J Surg Oncol. 2018;16(1):1. https://doi.org/10.1186/s12957-017-1299-9 PMid:29291744

Mook S, Schmidt MK, Weigelt B, Kreike B, Eekhout I, van de Vijver MJ, et al. The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age. Ann Oncol. 2010;21(4):717-22. https://doi.org/10.1093/ annonc/mdp388 PMid:19825882

de Ronde J, Wessels L, Wesseling J. Molecular subtyping of breast cancer: Ready to use? Lancet Oncol. 2010;11(4):306-7. https://doi.org/10.1016/s1470-2045(10)70036-x PMid:20359657

Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, et al. 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. https://doi.org/10.1016/j. breast.2003.09.007

PMid:25939896

Vallejos CS, Gómez HL, Cruz WR, Pinto JA, Dyer RR, Velarde R, et al. Breast cancer classification according to immunohistochemistry markers: Subtypes and association with clinicopathologic variables in a peruvian hospital database. Clin Breast Cancer. 2010;10(4):294-300. https://doi.org/10.3816/ cbc.2010.n.038 PMid:20705562

Denkert C, von Minckwitz G. Reply to Ki67 in breast cancer: A useful prognostic marker! Ann Oncol. 2014;25(2):542-3. https://doi.org/10.1093/annonc/mdt564 PMid:24431345

Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101(10):736- 50. https://doi.org/10.1093/jnci/djp082 PMid:19436038

Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, et al. Assessment of Ki67 in breast cancer: Recommendations from the international Ki67 in breast cancer working group. J Natl Cancer Inst. 2011;103(22):1656-64. https://doi.org/10.1093/jnci/djr393 PMid:21960707

Luporsi E, André F, Spyratos F, Martin PM, Jacquemier J, Penault-Llorca F, et al. 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;132(3):895-915. https://doi. org/10.1007/s10549-011-1837-z PMid:22048814

Polley MY, Leung SC, McShane LM, Gao D, Hugh JC, Mastropasqua MG, et al. An international Ki67 reproducibility study. J Natl Cancer Inst. 2013;105(24):1897-906. PMid:24203987

Published
2020-03-25
How to Cite
1.
Nikolov S, Enchev E, Minkov G, Dimitrov E, Ivanova K, Gulubova M, Vlaykova T, Yovtchev Y. The Role of the Molecular Subtypes in the Prognosis of Breast Cancer Patients. Open Access Maced J Med Sci [Internet]. 2020Mar.25 [cited 2020Oct.31];8(B):133-8. Available from: https://www.id-press.eu/mjms/article/view/4077