Skip to main content

Advertisement

SpringerLink
Log in

Thrombocytosis as a prognostic factor in inflammatory breast cancer

  • Clinical trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Platelets are essential components of hemostasis and also play an important role in the tumor microenvironment. The purposes of our research were to examine the role of thrombocytosis in inflammatory breast cancer (IBC) and to know which cytokine drives thrombocytosis.

Methods

We reviewed the medical records of 3654 patients with stage I–III breast cancer treated between 1998 and 2013, including 230 patients (6%) with IBC. We used Chi-squared test or Fisher’s exact test to compare the variables between patients with and without thrombocytosis. Multivariate Cox regression models were used to determine the association of thrombocytosis with overall survival. We also examined baseline serum cytokine levels in 81 patients with primary IBC to determine the association of inflammatory cytokines with thrombocytosis.

Results

We found that thrombocytosis was the only variable that predicted prognosis. Fifty-five patients (1.5%) had thrombocytosis. Thrombocytosis was more prevalent in patients with IBC than in those with non-IBC (3.4% vs. 1.4%, p = 0.015). In patients with IBC, thrombocytosis was associated with worse overall survival [hazard ratio 2.38, 95% confidence interval (CI) 1.05–5.4, p = 0.0378]. Circulating levels of growth-regulated oncogene (GRO) (odds ratio 1.003, 95% CI 1.001–1.005, p = 0.0019) and transforming growth factor β (TGF-β) (odds ratio 1.3, 95% CI 1.128–1.499, p = 0.0003) were associated with thrombocytosis.

Conclusions

Thrombocytosis was more prevalent in patients with IBC than in those with non-IBC and it was associated with poor prognosis. GRO and TGF-β were associated with thrombocytosis in IBC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65:5–29

    Article  PubMed  Google Scholar 

  2. Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  CAS  PubMed  Google Scholar 

  3. Lucci A, Hall CS, Lodhi AK et al (2012) Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol 13:688–695

    Article  PubMed  Google Scholar 

  4. Tefferi A, Thiele J, Orazi A et al (2007) Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 110:1092–1097

    Article  CAS  PubMed  Google Scholar 

  5. Silvis SE, Turkbas N, Doscherholmen A (1970) Thrombocytosis in patients with lung cancer. JAMA 211:1852–1853

    Article  CAS  PubMed  Google Scholar 

  6. Monreal M, Fernandez-Llamazares J, Pinol M et al (1998) Platelet count and survival in patients with colorectal cancer–a preliminary study. Thromb Haemost 79:916–918

    CAS  PubMed  Google Scholar 

  7. Stone RL, Nick AM, McNeish IA et al (2012) Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med 366:610–618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Borsig L (2008) The role of platelet activation in tumor metastasis. Expert Rev Anticancer Ther 8:1247–1255

    Article  CAS  PubMed  Google Scholar 

  9. Taucher S, Salat A, Gnant M et al (2003) Impact of pretreatment thrombocytosis on survival in primary breast cancer. Thromb Haemost 89:1098–1106

    CAS  PubMed  Google Scholar 

  10. Rajkumar A, Szallasi A (2013) Paraneoplastic thrombocytosis in breast cancer. Anticancer Res 33:4545–4546

    PubMed  Google Scholar 

  11. Hance KW, Anderson WF, Devesa SS et al (2005) Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst 97:966–975

    Article  PubMed  PubMed Central  Google Scholar 

  12. Fouad TM, Kogawa T, Liu DD et al (2015) Overall survival differences between patients with inflammatory and noninflammatory breast cancer presenting with distant metastasis at diagnosis. Breast Cancer Res Treat 152:407–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Dawood S, Merajver SD, Viens P et al (2011) International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann Oncol 22:515–523

    Article  CAS  PubMed  Google Scholar 

  14. Fouad TM, Kogawa T, Reuben JM, Ueno NT (2014) The role of inflammation in inflammatory breast cancer. Adv Exp Med Biol 816:53–73

    Article  CAS  PubMed  Google Scholar 

  15. van Golen KL, Wu ZF, Qiao XT et al (2000) RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells. Neoplasia 2:418–425

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hartman ZC, Yang XY, Glass O et al (2011) HER2 overexpression elicits a proinflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis. Can Res 71:4380–4391

    Article  CAS  Google Scholar 

  17. Benoy I, Salgado R, Colpaert C et al (2002) Serum interleukin 6, plasma VEGF, serum VEGF, and VEGF platelet load in breast cancer patients. Clin Breast Cancer 2:311–315

    Article  CAS  PubMed  Google Scholar 

  18. Ferrajoli A, Lee BN, Schlette EJ et al (2008) Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood 111:5291–5297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19:1423–1437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Koh CH, Bhoo-Pathy N, Ng KL et al (2015) Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer. Br J Cancer 113:150–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Azab B, Bhatt VR, Phookan J et al (2012) Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. Ann Surg Oncol 19:217–224

    Article  PubMed  Google Scholar 

  22. Liu X, Meng QH, Ye Y et al (2015) Prognostic significance of pretreatment serum levels of albumin, LDH and total bilirubin in patients with non-metastatic breast cancer. Carcinogenesis 36:243–248

    Article  PubMed  Google Scholar 

  23. Brown JE, Cook RJ, Lipton A, Coleman RE (2012) Serum lactate dehydrogenase is prognostic for survival in patients with bone metastases from breast cancer: a retrospective analysis in bisphosphonate-treated patients. Clin Cancer Res 18:6348–6355

    Article  CAS  PubMed  Google Scholar 

  24. Horsfall LJ, Rait G, Walters K et al (2011) Serum bilirubin and risk of respiratory disease and death. JAMA 305:691–697

    Article  CAS  PubMed  Google Scholar 

  25. Boehlen F, Clemetson KJ (2001) Platelet chemokines and their receptors: what is their relevance to platelet storage and transfusion practice? Transfus Med 11:403–417

    Article  CAS  PubMed  Google Scholar 

  26. Bechara C, Chai H, Lin PH et al (2007) Growth related oncogene-alpha (GRO-alpha): roles in atherosclerosis, angiogenesis and other inflammatory conditions. Med Sci Monit 13:RA87-90

    PubMed  Google Scholar 

  27. Wen Y, Giardina SF, Hamming D et al (2006) GROalpha is highly expressed in adenocarcinoma of the colon and down-regulates fibulin-1. Clin Cancer Res 12:5951–5959

    Article  CAS  PubMed  Google Scholar 

  28. Loukinova E, Dong G, Enamorado-Ayalya I et al (2000) Growth regulated oncogene-alpha expression by murine squamous cell carcinoma promotes tumor growth, metastasis, leukocyte infiltration and angiogenesis by a host CXC receptor-2 dependent mechanism. Oncogene 19:3477–3486

    Article  CAS  PubMed  Google Scholar 

  29. Salim JP, Goette NP, Lev PR et al (2009) Dysregulation of stromal derived factor 1/CXCR4 axis in the megakaryocytic lineage in essential thrombocythemia. Br J Haematol 144:69–77

    Article  CAS  PubMed  Google Scholar 

  30. Mallini P, Lennard T, Kirby J, Meeson A (2014) Epithelial-to-mesenchymal transition: what is the impact on breast cancer stem cells and drug resistance. Cancer Treat Rev 40:341–348

    Article  CAS  PubMed  Google Scholar 

  31. Cohen EN, Gao H, Anfossi S et al (2015) Inflammation mediated metastasis: immune induced epithelial-to-mesenchymal transition in inflammatory breast cancer cells. PLoS ONE 10:e0132710

    Article  PubMed  PubMed Central  Google Scholar 

  32. Van Laere SJ, Ueno NT, Finetti P et al (2013) Uncovering the molecular secrets of inflammatory breast cancer biology: an integrated analysis of three distinct affymetrix gene expression datasets. Clin Cancer Res 19:4685–4696

    Article  PubMed  Google Scholar 

  33. Labelle M, Begum S, Hynes RO (2011) Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 20:576–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cho MS, Bottsford-Miller J, Vasquez HG et al (2012) Platelets increase the proliferation of ovarian cancer cells. Blood 120:4869–4872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by Japanese Cancer Society (Grant Name: My Oncology Dream award 2014). Additional support was provided by the Morgan Welch Inflammatory Breast Cancer Research Program, and State of Texas Rare and Aggressive Breast Cancer Research Program Grant.

Author information

Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1220 Holcombe Blvd, Houston, TX, 77030, USA

    Kenichi Harano, Takahiro Kogawa, Bora Lim & Naoto T. Ueno

  2. Morgan Welch Inflammatory Breast Cancer Research Program, The University of Texas MD Anderson Cancer Center, 1220 Holcombe Blvd, Houston, TX, 77030, USA

    Kenichi Harano, Evan N. Cohen, Bora Lim, James M. Reuben & Naoto T. Ueno

  3. Department of Medical Oncology, Nippon Medical School Musashikosugi Hospital, 1-396, Kosugi-cho, Nakahara-ku, Kawasaki City, Kanagawa, 211-8533, Japan

    Kenichi Harano

  4. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA

    Jimin Wu & Ying Yuan

  5. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Evan N. Cohen & James M. Reuben

  6. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Unit 3552, Houston, TX, 77030, USA

    Naoto T. Ueno

Authors
  1. Kenichi Harano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takahiro Kogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jimin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ying Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Evan N. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bora Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. James M. Reuben
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Naoto T. Ueno
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Naoto T. Ueno.

Ethics declarations

Conflict of interest

Ying Yuan is a consultant of Agenus. Other authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harano, K., Kogawa, T., Wu, J. et al. Thrombocytosis as a prognostic factor in inflammatory breast cancer. Breast Cancer Res Treat 166, 819–832 (2017). https://doi.org/10.1007/s10549-017-4463-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-017-4463-6

Keywords

Search

Navigation