Venous Thromboembolism Risk and Coagulation Markers in Rare Breast Tumors: A Perspective
DOI:
https://doi.org/10.67224/ioasdjmps.2026.v03i02.007Keywords:
Venous thromboembolism, Coagulation markers, Rare breast tumors, Hypercoagulability, Thrombosis riskAbstract
Venous thromboembolism (VTE) is a frequent and serious complication in cancer patients, with risk varying according to tumor subtype and biology. Rare breast tumors, including metaplastic, secretory, adenoid cystic, and phyllodes tumors, remain understudied regarding their association with coagulation abnormalities and thrombotic risk. This perspective synthesizes current knowledge on the pathophysiology of coagulation activation, the prognostic value of coagulation markers such as D-dimer and thrombin generation, and the clinical implications for VTE risk management in patients with rare breast tumors. Recognizing the distinct coagulation profiles and thrombotic tendencies in these tumors is critical to refining risk stratification and guiding personalized thromboprophylaxis. Future research focusing on molecular mechanisms and biomarker validation is essential to improve clinical outcomes and reduce thrombotic morbidity in this unique patient population.
References
1. Donnellan, E., & Khorana, A. A. (2017). Cancer and venous thromboembolic disease: a review. The Oncologist, 22(2), 199-207. doi: 10.1634/theoncologist.2016-0214.
2. Fowler, C., & Pastores, S. M. (2025). Venous thromboembolic events in cancer immunotherapy: a narrative review. Journal of Clinical Medicine, 14(14), 4926. https://doi.org/10.3390/jcm14144926
3. Lyman, G. H. (2011). Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thromboprophylaxis. Cancer, 117(7), 1334-1349. doi: 10.1002/cncr.25714.
4. Obeagu, E. I. (2025). N2 neutrophils and tumor progression in breast cancer: molecular pathways and implications. Breast Cancer: Targets and Therapy, 639-651. doi: 10.2147/BCTT.S542787.
5. Obeagu, E. I., & Obeagu, G. U. (2024). Exploring the profound link: breastfeeding’s impact on alleviating the burden of breast cancer–a review. Medicine, 103(15), e37695. doi: 10.1097/MD.0000000000037695.
6. Suzuki, S., Seino, M., Sato, H., Kawai, M., Saito, Y., Saito, K., ... & Fukui, T. (2025). Malignant phyllodes tumors: diagnostic, investigative and therapeutic challenges. Encyclopedia, 5(4), 157. https://doi.org/10.3390/encyclopedia5040157
7. Reimer, T. (2008). Management of rare histological types of breast tumours. Breast Care, 3(3), 190-196. doi: 10.1159/000136826.
8. Mitrugno, A., Tormoen, G. W., Kuhn, P., & McCarty, O. J. (2016). The prothrombotic activity of cancer cells in the circulation. Blood reviews, 30(1), 11-19. doi: 10.1016/j.blre.2015.07.001.
9. Neilson, T., Li, Z., Minami, C., & Myers, S. P. (2025). Adenoid cystic carcinoma of the breast: a narrative review and update on management. Cancers, 17(7), 1079. https://doi.org/10.3390/cancers17071079
10. Moik, F., & Ay, C. (2022). Hemostasis and cancer: Impact of haemostatic biomarkers for the prediction of clinical outcomes in patients with cancer. Journal of Thrombosis and Haemostasis, 20(12), 2733-2745. doi: 10.1111/jth.15880.
11. Obeagu, E. I., & Obeagu, G. U. (2024). Lymphocyte infiltration in breast cancer: a promising prognostic indicator. Medicine, 103(49), e40845. doi: 10.1097/MD.0000000000040845.
12. Ayandipo, O., Ajagbe, O., Afolabi, A., Ogundiran, T., Orunmuyi, A., Soneye, O., ... & Soneye, O. Y. (2023). Venous Thromboembolism in Hospitalized Patients with Surgical Breast Cancer: Risks and Outcomes. Cureus, 15(7).: e42096. doi: 10.7759/cureus.42096.
13. Donnellan, E., & Khorana, A. A. (2017). Cancer and venous thromboembolic disease: a review. The Oncologist, 22(2), 199-207. doi: 10.1634/theoncologist.2016-0214.
14. Obeagu, E. I., & Obeagu, G. U. (2024). Breast cancer: A review of risk factors and diagnosis. Medicine, 103(3), e36905. doi: 10.1097/MD.0000000000036905.
15. Caine GJ, Stonelake PS, Lip GY, Kehoe ST. (2002). The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia., 4(6):465-73. doi: 10.1038/sj.neo.7900263.
16. Wrzeszcz, K., Rhone, P., Kwiatkowska, K., & Ruszkowska-Ciastek, B. (2023). Hypercoagulability state combined with post-treatment hypofibrinolysis in invasive breast cancer: a seven-year follow-up evaluating disease-free and overall survival. Life, 13(5), 1106. doi: 10.3390/life13051106.
17. Hassan, N., Efing, J., Kiesel, L., Bendas, G., & Götte, M. (2023). The tissue factor pathway in cancer: overview and role of heparan sulfate proteoglycans. Cancers, 15(5), 1524. doi: 10.3390/cancers15051524.
18. Hisada, Y., & Mackman, N. (2021). Tissue factor and extracellular vesicles: activation of coagulation and impact on survival in cancer. Cancers, 13(15), 3839. doi: 10.3390/cancers13153839.
19. Qureshi, M., Alam, M. T., & Unar, A. (2025). The role of tissue Factor-Positive microparticles in gynecological Cancer-Associated disseminated intravascular coagulation: molecular mechanisms and clinical implications. Onco, 5(3), 33. https://doi.org/10.3390/onco5030033
20. Kore, R. A., & Abraham, E. C. (2014). Inflammatory cytokines, interleukin-1 beta and tumor necrosis factor-alpha, upregulated in glioblastoma multiforme, raise the levels of CRYAB in exosomes secreted by U373 glioma cells. Biochemical and biophysical research communications, 453(3), 326-331. doi: 10.1016/j.bbrc.2014.09.068.
21. Sprague, A. H., & Khalil, R. A. (2009). Inflammatory cytokines in vascular dysfunction and vascular disease. Biochemical pharmacology, 78(6), 539-552. doi: 10.1016/j.bcp.2009.04.029.
22. Obeagu, E. I., & Obeagu, G. U. (2024). Exploring neutrophil functionality in breast cancer progression: a review. Medicine, 103(13), e37654. doi: 10.1097/MD.0000000000037654.
23. Kim, G. E., Kim, J. H., Lee, K. H., Choi, Y. D., Lee, J. S., Lee, J. H., ... & Yoon, J. H. (2012). Stromal matrix metalloproteinase-14 expression correlates with the grade and biological behavior of mammary phyllodes tumors. Applied Immunohistochemistry & Molecular Morphology, 20(3), 298-303. doi: 10.1097/PAI.0b013e318235a132.
24. Wang, K., Wu, F., Seo, B. R., Fischbach, C., Chen, W., Hsu, L., & Gourdon, D. (2017). Breast cancer cells alter the dynamics of stromal fibronectin-collagen interactions. Matrix Biology, 60, 86-95. doi: 10.1016/j.matbio.2016.08.001.
25. Wrzeszcz, K., Rhone, P., Kwiatkowska, K., & Ruszkowska-Ciastek, B. (2023). Hypercoagulability state combined with post-treatment hypofibrinolysis in invasive breast cancer: a seven-year follow-up evaluating disease-free and overall survival. Life, 13(5), 1106. doi: 10.3390/life13051106.
26. Ayana, S., Aynalem, M., Adane, T., & Shiferaw, E. (2025). Coagulation profiles of breast cancer patients attending at cancer treatment centres in Northwest Ethiopia 2023: a comparative cross-sectional study. Scientific reports, 15(1), 16979. doi: 10.1038/s41598-025-02104-w.
27. Riondino, S., Ferroni, P., Zanzotto, F. M., Roselli, M., & Guadagni, F. (2019). Predicting VTE in cancer patients: candidate biomarkers and risk assessment models. Cancers, 11(1), 95. doi: 10.3390/cancers11010095.
28. Canonico, M. E., Santoro, C., Avvedimento, M., Giugliano, G., Mandoli, G. E., Prastaro, M., ... & Esposito, G. (2022). Venous thromboembolism and cancer: a comprehensive review from pathophysiology to novel treatment. Biomolecules, 12(2), 259. https://doi.org/10.3390/biom12020259
29. Khorana, A. A., & Connolly, G. C. (2009). Assessing risk of venous thromboembolism in the patient with cancer. Journal of Clinical Oncology, 27(29), 4839-4847. doi: 10.1200/JCO.2009.22.3271.
30. Gran, O. V., Brækkan, S. K., Paulsen, B., Skille, H., & Hansen, J. B. (2016). D-dimer measured at first venous thromboembolism is associated with future risk of cancer. Haematologica, 101(12), e473-e475. doi: 10.3324/haematol.2016.151712.
31. Obeagu, E. I. (2025). Mentzer Index in breast cancer: Insights into anemia and tumor progression–a narrative review. Medicine, 104(40), e45114. doi: 10.1097/MD.0000000000045114.
32. Depasse, F., Binder, N. B., Mueller, J., Wissel, T., Schwers, S., Germer, M., ... & Turecek, P. L. (2021). Thrombin generation assays are versatile tools in blood coagulation analysis: a review of technical features, and applications from research to laboratory routine. Journal of Thrombosis and Haemostasis, 19(12), 2907-2917. doi: 10.1111/jth.15529.
33. Binder, N. B., Depasse, F., Mueller, J., Wissel, T., Schwers, S., Germer, M., ... & Turecek, P. L. (2021). Clinical use of thrombin generation assays. Journal of Thrombosis and Haemostasis, 19(12), 2918-2929. doi: 10.1111/jth.15538.
34. Asakura, H., Hifumi, S., Jokaji, H., Saito, M., Kumabashiri, I., Uotani, C., ... & Matsuda, T. (1992). Prothrombin fragment F1+ 2 and thrombin—antithrombin III complex are useful markers of the hypercoagulable state in atrial fibrillation. Blood coagulation & fibrinolysis, 3(4), 469-473.
35. Lundbech, M., Krag, A. E., Christensen, T. D., & Hvas, A. M. (2020). Thrombin generation, thrombin-antithrombin complex, and prothrombin fragment F1+ 2 as biomarkers for hypercoagulability in cancer patients. Thrombosis research, 186, 80-85. doi: 10.1016/j.thromres.2019.12.018.
36. Lawrence, R., Watters, M., Davies, C. R., Pantel, K., & Lu, Y. J. (2023). Circulating tumour cells for early detection of clinically relevant cancer. Nature Reviews Clinical Oncology, 20(7), 487-500. doi: 10.1038/s41571-023-00781-y.
37. Obeagu, E. I. (2025). Neutrophil-driven tumor inflammation in breast cancer: Pathways and therapeutic implications: A narrative review. Medicine, 104(25), e43024. doi: 10.1097/MD.0000000000043024.
38. Khan, U. T., Walker, A. J., Baig, S., Card, T. R., Kirwan, C. C., & Grainge, M. J. (2017). Venous thromboembolism and mortality in breast cancer: cohort study with systematic review and meta-analysis. BMC cancer, 17(1), 747. doi: 10.1186/s12885-017-3719-1.
39. Kuderer, N. M., & Lyman, G. H. (2014). Guidelines for treatment and prevention of venous thromboembolism among patients with cancer. Thrombosis research, 133, S122-S127. doi: 10.1016/S0049-3848(14)50021-7.
40. Binder, N. B., Depasse, F., Mueller, J., Wissel, T., Schwers, S., Germer, M., ... & Turecek, P. L. (2021). Clinical use of thrombin generation assays. Journal of Thrombosis and Haemostasis, 19(12), 2918-2929. doi: 10.1111/jth.15538.
41. Nicola, A., Crowley, M., & See, M. (2021). A novel algorithm to reduce VTE in peri-operative patients on tamoxifen. The Breast, 58, 88-92. doi: 10.1016/j.breast.2021.04.009.
42. Zalunardo, B., Panzavolta, C., Bigolin, P., & Visonà, A. (2022). Multidisciplinary care for the prevention and treatment of venous thromboembolism in patients with cancer-associated thrombosis (CAT): impact of educational interventions on CAT-related events and on patients’ and clinicians’ awareness. Life, 12(10), 1594. doi: 10.3390/life12101594.
43. Zhou, H., Chen, H., Cheng, C., Wu, X., Ma, Y., Han, J., ... & Wang, Q. (2021). A quality evaluation of the clinical practice guidelines on breast cancer using the RIGHT checklist. Annals of Translational Medicine, 9(14), 1174. doi: 10.21037/atm-21-2884.
44. Obeagu, E. I. (2025). Thromboinflammatory pathways in breast cancer: clinical and molecular insights into venous thromboembolism risk–a narrative review. Annals of Medicine and Surgery, 87(9), 5822-5828. doi: 10.1097/MS9.0000000000003644.
45. Londero, A. P., Bertozzi, S., Cedolini, C., Neri, S., Bulfoni, M., Orsaria, M., ... & Barillari, G. (2022). Incidence and risk factors for venous thromboembolism in female patients undergoing breast surgery. Cancers, 14(4), 988. doi: 10.3390/cancers14040988.
46. Attard, L. M., Gatt, A., Bertoletti, L., Delluc, A., & Riva, N. (2022). Direct oral anticoagulants for the prevention and acute treatment of cancer-associated thrombosis. Vascular Health and Risk Management, 793-807. doi: 10.2147/VHRM.S271411.
47. Wrzeszcz, K., Rhone, P., Kwiatkowska, K., & Ruszkowska-Ciastek, B. (2023). Hypercoagulability state combined with post-treatment hypofibrinolysis in invasive breast cancer: a seven-year follow-up evaluating disease-free and overall survival. Life, 13(5), 1106. doi: 10.3390/life13051106.
48. Sherman S, Shats O, Fleissner E, Bascom G, Yiee K, Copur M, Crow K, Rooney J, Mateen Z, Ketcham MA, Feng J, Sherman A, Gleason M, Kinarsky L, Silva-Lopez E, Edney J, Reed E, Berger A, Cowan K. (2011). Multicenter breast cancer collaborative registry. Cancer Inform.; 10:217-26. doi: 10.4137/CIN.S7845.
49. Haut, E. R., Aboagye, J. K., Shaffer, D. L., Wang, J., Hobson, D. B., Yenokyan, G., ... & Lau, B. D. (2018). Effect of real-time patient-centered education bundle on administration of venous thromboembolism prevention in hospitalized patients. JAMA network open, 1(7), e184741. doi: 10.1001/jamanetworkopen.2018.4741.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Emmanuel Ifeanyi Obeagu (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
