Background. An elevated platelet count is often associated with malignancies, and it has been confirmed as an adverse prognostic factor in various cancers including early stage breast cancer. We sought to determine if thrombocytosis is also a prognostic factor in metastatic breast cancer. Patients and Methods. The records of 165 metastatic breast cancer patients with complete follow-up that had thrombocytosis or normal platelet counts were reviewed. Kaplan-Meier curves were constructed, and the survivals of the two groups were compared using the LogRank test. A Cox regression analysis was used to determine if thrombocytosis is an independent factor for overall and progression free survival. Results. There was a statistically significant difference in overall and progression free survival favoring the normal platelets group (LogRank test and 0.008, resp.). Thrombocytosis remained a significant adverse prognostic factor in multivariate analysis. Other independent prognostic factors for overall survival included age, ER/PR status, and grade. Conclusion. Thrombocytosis represents an independent adverse prognostic factor in patients with metastatic breast cancer. Thus metastatic breast cancer joins a range of cancers in which this easily measurable value can be used for clinical prognostication. Further use as a predictive value for specific treatments has a rationale and deserves to be investigated. 1. Introduction Platelets are important cellular particles for hemostasis and vascular integrity. They are produced from bone marrow precursor cells, megakaryocytes. Abnormalities in their normal circulating number either in the form of thrombocytosis or thrombocytopenia are associated with many pathologic conditions [1]. Cytokines that stimulate thrombopoiesis are often elevated in cancer, and as a result, various cancers have been associated with thrombocytosis. In addition thrombocytosis has been found to be an adverse prognostic factor in many types of common cancers. Breast cancer is the most common female malignancy. When localized, it is treated with surgery and often with adjuvant therapies to decrease the risk of local or systemic recurrences [2]. Both adjuvant therapies and therapies in the metastatic disease setting are guided by biologic characteristics such as hormone receptors and growth factor Her-2 expression. These characteristics possess also prognostic information, but additional markers are needed to further promote prognostication of breast cancer. In early stage breast cancer patients undergoing chemotherapy in five clinical trials of the
References
[1]
J. S. Bleeker and W. J. Hogan, “Thrombocytosis: diagnostic evaluation, thrombotic risk stratification, and risk-based management strategies,” Thrombosis, vol. 2011, Article ID 536062, 16 pages, 2011.
[2]
L. F. Hernandez-Aya and A. M. Gonzalez-Angulo, “Adjuvant systemic therapies in breast cancer,” Surgical Clinics of North America, vol. 93, no. 2, pp. 473–491, 2013.
[3]
S. Taucher, A. Salat, M. Gnant et al., “Impact of pretreatment thrombocytosis on survival in primary breast cancer,” Thrombosis and Haemostasis, vol. 89, no. 6, pp. 1098–1106, 2003.
[4]
G. Scatter, J. Lee, J. M. S. Bartlett, D. J. Slamon, and M. F. Press, “Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations,” Journal of Clinical Oncology, vol. 27, no. 8, pp. 1323–1333, 2009.
[5]
B. Dawson-Saunders and R. G. Trapp, Basic and Clinical Biostatistics, Appleton and Lange, Norwalk, Conn, USA, 1994.
[6]
J. F. Lawless, Statistical Models and Methods for Lifetime Data, John Wiley and sons, New York, NY, USA, 1982.
[7]
J. Levin and C. L. Conley, “Thrombocytosis associated with malignant disease,” Archives of Internal Medicine, vol. 114, pp. 497–500, 1964.
[8]
D. J. Slamon, B. Leyland-Jones, S. Shak et al., “Use of chemotherapy plus a monoclonal antibody against her2 for metastatic breast cancer that overexpresses HER2,” The New England Journal of Medicine, vol. 344, no. 11, pp. 783–792, 2001.
[9]
V. Valero, J. Forbes, M. D. Pegram et al., “Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 Study): two highly active therapeutic regimens,” Journal of Clinical Oncology, vol. 29, no. 2, pp. 149–156, 2011.
[10]
H. Shimada, G. Oohira, S.-I. Okazumi et al., “Thrombocytosis associated with poor prognosis in patients with esophageal carcinoma,” Journal of the American College of Surgeons, vol. 198, no. 5, pp. 737–741, 2004.
[11]
S. G. Hwang, K. M. Kim, J. H. Cheong, et al., “Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of gastric cancer,” European Journal of Surgical Oncology, vol. 38, pp. 562–567, 2012.
[12]
N. P. Symbas, M. F. Townsend, R. El-Galley, T. E. Keane, S. D. Graham, and J. A. Petros, “Poor prognosis associated with thrombocytosis in patients with renal cell carcinoma,” BJU International, vol. 86, no. 3, pp. 203–207, 2000.
[13]
R. L. Stone, A. M. Nick, I. A. McNeish et al., “Paraneoplastic thrombocytosis in ovarian cancer,” The New England Journal of Medicine, vol. 366, no. 7, pp. 610–618, 2012.
[14]
E. Hernandez, M. Lavine, C. J. Dunton, et al., “Poor prognosis associated with thrombocytosis in patients with cervical cancer,” Cancer, vol. 69, pp. 2975–2977, 1992.
[15]
I. Domínguez, S. Crippa, S. P. Thayer et al., “Preoperative platelet count and survival prognosis in resected pancreatic ductal adenocarcinoma,” World Journal of Surgery, vol. 32, no. 6, pp. 1051–1056, 2008.
[16]
M. Ikeda, H. Furukawa, H. Imamura et al., “Poor prognosis associated with thrombocytosis in patients with gastric cancer,” Annals of Surgical Oncology, vol. 9, no. 3, pp. 287–291, 2002.
[17]
T. Gungor, M. Kanat-Pektas, A. Sucak, and L. Mollamahmutoglu, “The role of thrombocytosis in prognostic evaluation of epithelial ovarian tumors,” Archives of Gynecology and Obstetrics, vol. 279, no. 1, pp. 53–56, 2009.
[18]
B. Paule, J. Belot, C. Rudant, C. Coulombel, and C. C. Abbou, “The importance of IL-6 protein expression in primary human renal cell carcinoma: an immunohistochemical study,” Journal of Clinical Pathology, vol. 53, no. 5, pp. 388–390, 2000.
[19]
J. Nakashima, M. Tachibana, Y. Horiguchi et al., “Serum interleukin 6 as a prognostic factor in patients with prostate cancer,” Clinical Cancer Research, vol. 6, no. 7, pp. 2702–2706, 2000.
[20]
I. Benoy, R. Salgado, C. Colpaert, R. Weytjens, P. B. Vermeulen, and L. Y. Dirix, “Serum interleukin 6, plasma VEGF, serum VEGF, and VEGF platelet load in breast cancer patients,” Clinical Breast Cancer, vol. 2, no. 4, pp. 311–315, 2002.
[21]
D. Buergy, F. Wenz, C. Groden, and M. A. Brockmann, “Tumor-platelet interaction in solid tumors,” International Journal of Cancer, vol. 130, no. 12, pp. 2747–2760, 2012.
[22]
B. Ho-Tin-Noé, M. Demers, and D. D. Wagner, “How platelets safeguard vascular integrity,” Journal of Thrombosis and Haemostasis, vol. 9, supplement 1, pp. 56–65, 2011.
[23]
B. Ho-Tin-Noé, C. Carbo, M. Demers, S. M. Cifuni, T. Goerge, and D. D. Wagner, “Innate immune cells induce hemorrhage in tumors during thrombocytopenia,” American Journal of Pathology, vol. 175, no. 4, pp. 1699–1708, 2009.
[24]
L. J. Gay and B. Felding-Habermann, “Contribution of platelets to tumour metastasis,” Nature Reviews Cancer, vol. 11, no. 2, pp. 123–134, 2011.
[25]
E. Gunsilius, A. Petzer, G. Stockhammer et al., “Thrombocytes ave the major source for soluble vascular endothelial growth factor in peripheral blood,” Oncology, vol. 58, no. 2, pp. 169–174, 2000.
[26]
M. Labelle, S. Begum, and R. Hynes, “Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis,” Cancer Cell, vol. 20, no. 5, pp. 576–590, 2011.
[27]
R. Kalluri and R. A. Weinberg, “The basics of epithelial-mesenchymal transition,” Journal of Clinical Investigation, vol. 119, no. 6, pp. 1420–1428, 2009.
[28]
T. M. H. Niers, D. J. Richel, J. C. M. Meijers, and R. O. Schlingemann, “Vascular endothelial growth factor in the circulation in cancer patients may not be a relevant biomarker,” PLoS One, vol. 6, no. 5, Article ID e19873, 2011.
[29]
D. Y. Heng, M. J. MacKenzie, U. N. Vaishampayan, et al., “Primary anti-vascular endothelial growth factor (VEGF)-refractory metastatic renal cell carcinoma: clinical characteristics, risk factors, and subsequent therapy,” Annals of Oncology, vol. 23, pp. 1549–1555, 2012.
