Platelet Activation and Platelet Indices as Markers for Disease Progression in Women with Breast Cancer Platelets and Prognosis of Breast Cancer

Main Article Content

Yousra Tera https://orcid.org/0000-0002-4770-6663
Hanan Azzam https://orcid.org/0000-0001-5379-5511
Nashwa Abousamra https://orcid.org/0000-0001-7418-8585
Marwa Zaki https://orcid.org/0000-0001-5347-6705
Ahmed Eltantawy
Mohamed Awad
Hayam Ghoneim
Maha Othman https://orcid.org/0000-0001-7562-203X

Keywords

Breast cancer, Platelet activation, Platelet indices, Metastasis, Cancer prognosis

Abstract

Background:  Several studies reported the role platelet activation, platelet volume (MPV) and other  Indices in breast cancer but the data is inconsistent and/or diverse. The aim of this study was to systematically evaluate the role of platelet activation and platelet volume indices in women with BC as predictors for cancer progression and poor prognosis.


Methods: Patients were recruited from our local oncology center between 2019 to 2020 following ethics approval. 80 patients with locally invasive BC, 20 metastatic and 100 controls were recruited. ADP-induced platelet activation was assessed by light-transmission aggregometry. Platelet P-selectin (CD62P) expression with and without ADP stimulation was assessed by flow cytometry. A comprehensive analysis of platelet count and platelet volume indices (PVIs) (MPV, PDW, MPV/P and PDW/P) was conducted. Data were analyzed in relation to tumor pathology, hormone receptors (ER, PR, HER-2) and proliferation index Ki-67. Regression analyses were conducted for the prediction of poor prognosis, tumor aggression and metastatic potential.


Results: We found a significant increase in platelet aggregation (MA), CD62P expression, CD62P+ADP, MPV, PDW, MPV/P and PDW/P in the metastatic group compared to the locally invasive group.  Univariate regression analysis showed significance for  ADP, MA,  CD62P+ADP,   MPV   and   PDW/P. 


Conclusion: MPV/P and PDW/P can be used as simple low-cost predictors for cancer progression and poor prognosis. We conclude platelet activation and specific platelet indices can help predict prognosis in females with BC.

References

1. Dawoud MM, Abdelaziz KK-E, Alhanafy AM, Ali MS-d, Elkhouly EAB. Clinical Significance of Immunohistochemical Expression of Neuropeptide Y1 Receptor in Patients With Breast Cancer in Egypt. Applied Immunohistochemistry & Molecular Morphology. 2021;29(4):277-86. doi: 10.1097/pai.0000000000000877.
2. DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA: a cancer journal for clinicians. 2014;64(4):252-71. doi: 10.3322/caac.21235.
3. Kraeima J, Siesling S, Vliegen I, Klaase J, IJzerman MJ. Individual risk profiling for breast cancer recurrence: towards tailored follow-up schemes. British journal of cancer. 2013;109(4):866-71. doi: 10.1038/bjc.2013.401.
4. Cantrell R, Palumbo JS. The thrombin–inflammation axis in cancer progression. Thrombosis Research. 2020;191:S117-S22. doi: 10.1016/S0049-3848(20)30408-4.
5. Yan M, Jurasz P. The role of platelets in the tumor microenvironment: from solid tumors to leukemia. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2016;1863(3):392-400. doi: 10.1016/j.bbamcr.2015.07.008.
6. Radziwon-Balicka A, Moncada de la Rosa C, Jurasz P. Platelet-associated angiogenesis regulating factors: a pharmacological perspective. Canadian journal of physiology and pharmacology. 2012;90(6):679-88. doi: 10.1139/y2012-036.
7. Lal I, Dittus K, Holmes CE. Platelets, coagulation and fibrinolysis in breast cancer progression. Breast Cancer Research. 2013;15(4):1-11. doi: 10.1186/bcr3425.
8. Stoiber D, Assinger A. Platelet-leukocyte interplay in cancer development and progression. Cells. 2020;9(4):855. doi: 10.3390/cells9040855.
9. Gong L, Cai Y, Zhou X, Yang H. Activated platelets interact with lung cancer cells through P-selectin glycoprotein ligand-1. Pathology & Oncology Research. 2012;18(4):989-96. doi:10.1007/s12253-012-9531-y.
10. Stone RL, Nick AM, McNeish IA, Balkwill F, Han HD, Bottsford-Miller J, et al. Paraneoplastic thrombocytosis in ovarian cancer. New England Journal of Medicine. 2012;366(7):610-8. doi: 10.1056/NEJMoa1110352.
11. Varon D, Shai E. Role of platelet-derived microparticles in angiogenesis and tumor progression. Discovery medicine. 2009;8(43):237-41.
12. Kuter DJ. Managing thrombocytopenia associated with cancer chemotherapy. Oncology. 2015;29(4):282-94.
13. Lu F, Pan S, Qi Y, Li X, Wang J. The Clinical Application Value of RDW, CA153, and MPV in Breast Cancer. Clinical Laboratory. 2021;67(2). doi: 10.7754/Clin.Lab.2020.200507.
14. Diamond DM, Campbell AM, Park CR, Halonen J, Zoladz PR. The temporal dynamics model of emotional memory processing: a synthesis on the neurobiological basis of stress-induced amnesia, flashbulb and traumatic memories, and the Yerkes-Dodson law. Neural plasticity. 2007;2007. doi: 10.1155/2007/60803.
15. Shen X-B, Wang Y, Shan B-J, Lin L, Hao L, Liu Y, et al. Prognostic significance of platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) during etoposide-based first-line treatment in small cell lung cancer patients. Cancer management and research. 2019;11:8965. doi: 10.2147/CMAR.S215361.
16. Menter DG, Tucker SC, Kopetz S, Sood AK, Crissman JD, Honn KV. Platelets and cancer: a casual or causal relationship: revisited. Cancer and Metastasis Reviews. 2014;33(1):231-69. doi: 10.1007/s10555-014-9498-0.
17. Gu M, Zhai Z, Huang L, Zheng W, Zhou Y, Zhu R, et al. Pre-treatment mean platelet volume associates with worse clinicopathologic features and prognosis of patients with invasive breast cancer. Breast cancer. 2016;23(5):752-60. doi: 10.1007/s12282-015-0635-6.
18. Takeuchi H, Abe M, Takumi Y, Hashimoto T, Kobayashi R, Osoegawa A, et al. The prognostic impact of the platelet distribution width-to-platelet count ratio in patients with breast cancer. PloS one. 2017;12(12):e0189166. doi: 10.1371/journal.pone.0189166.
19. Cooke NM, Egan K, McFadden S, Grogan L, Breathnach OS, O'Leary J, et al. Increased platelet reactivity in patients with late‐stage metastatic cancer. Cancer medicine. 2013;2(4):564-70. doi: 10.1002/cam4.86.
20. Toth B, Liebhardt S, Steinig K, Ditsch N, Rank A, Bauerfeind I, et al. Platelet-derived microparticles and coagulation activation in breast cancer patients. Thrombosis and haemostasis. 2008;100(10):663-9.
21. Zhang R, Guo H, Xu J, Li B, Liu Y-J, Cheng C, et al. Activated platelets inhibit hepatocellular carcinoma cell differentiation and promote tumor progression via platelet-tumor cell binding. Oncotarget. 2016;7(37):60609. doi: 10.18632/oncotarget.11300.
22. Kedzierska M, Czernek U, Szydłowska-Pazera K, Potemski P, Piekarski J, Jeziorski A, et al. The changes of blood platelet activation in breast cancer patients before surgery, after surgery, and in various phases of the chemotherapy. Platelets. 2013;24(6):462-8. doi: 10.3109/09537104.2012.711866.
23. Holmes CE, Levis JE, Schneider DJ, Bambace NM, Sharma D, Lal I, et al. Platelet phenotype changes associated with breast cancer and its treatment. Platelets. 2016;27(7):703-11. doi: 10.3109/09537104.2016.1171302.
24. Singla T, Singla G, Ranga S, Singla S, Arora R. Role of platelet aggregation in metastatic breast cancer patients. Indian Journal of Pathology and Microbiology. 2020;63(4):564. doi: 10.4103/IJPM.IJPM_817_19.
25. Inwald, E., Klinkhammer-Schalke, M., Hofstädter, F., Zeman, F., Koller, M., Gerstenhauer, M., & Ortmann, O. (2013). Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast cancer research and treatment, 139(2), 539-552. doi: 10.1007/s10549-013-2560-8.

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