Breast Cancer Research and Treatment

, Volume 138, Issue 2, pp 621–631

Chronic comorbid conditions associated with risk of febrile neutropenia in breast cancer patients treated with chemotherapy

  • Victoria M. Chia
  • John H. Page
  • Roberto Rodriguez
  • Su-Jau Yang
  • Julie Huynh
  • Chun Chao
Epidemiology

Abstract

Chemotherapy-induced febrile neutropenia (FN) is associated with increased patient mortality and health care costs. Comorbid conditions such as liver and renal dysfunction have been linked to increased risk of FN. However, the effects of other chronic comorbid conditions on risk of FN have not been well studied. To examine the association between chronic comorbid conditions and FN in breast cancer patients, we identified incident breast cancer patients from 2000 to 2009 treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. Patients who received primary prophylactic granulocyte colony-stimulating factor (G-CSF) were excluded. We assessed history of comorbid conditions prior to cancer diagnosis using ICD-9 codes and disease registries. FN events were identified in the first chemotherapy cycle using a combination of ICD-9 codes and hospital discharge diagnoses. For each comorbid condition, propensity scores that included patient characteristics and other predisposing comorbid conditions were calculated and adjusted for in Cox models to determine associations between that comorbid condition and FN. We also evaluated secondary models that additionally adjusted for cancer stage, baseline absolute neutrophil count (ANC), chemotherapy regimen, and dose reductions. A total of 7,127 breast cancer patients were included; median age was 55 years, and the majority had localized (47 %) or regional (49 %) disease at diagnosis. In the first chemotherapy cycle, 335 (4.7 %) patients developed FN. Congestive heart failure (HR = 3.0; 95 % CI: 1.3–5.9), osteoarthritis (HR = 2.0; 95 % CI: 1.4–2.8), previous cancer (HR = 3.4; 95 % CI: 1.2–7.5), and thyroid disorder (HR = 1.6; 95 % CI: 1.1–2.3) were associated with increased risk of FN. These estimates were similar to those from secondary models that also adjusted for additional cancer and treatment-related covariates. Our findings suggest that several chronic comorbid conditions may be associated with risk of FN. This information, if confirmed by others, may aid clinical decision making with respect to use of prophylactic G-CSF during chemotherapy treatment.

Keywords

Breast cancer Comorbidities Febrile neutropenia Neutropenia 

Supplementary material

10549_2013_2454_MOESM1_ESM.doc (78 kb)
Supplementary material 1 (DOC 78 kb)

References

  1. 1.
    Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH (2006) Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 106(10):2258–2266. doi:10.1002/cncr.21847 PubMedCrossRefGoogle Scholar
  2. 2.
    Caggiano V, Weiss RV, Rickert TS, Linde-Zwirble WT (2005) Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy. Cancer 103(9):1916–1924. doi:10.1002/cncr.20983 PubMedCrossRefGoogle Scholar
  3. 3.
    Lyman GH, Michels SL, Reynolds MW, Barron R, Tomic KS, Yu J (2010) Risk of mortality in patients with cancer who experience febrile neutropenia. Cancer 116(23):5555–5563. doi:10.1002/cncr.25332 PubMedCrossRefGoogle Scholar
  4. 4.
    Lyman GH, Kuderer NM (2003) Epidemiology of febrile neutropenia. Support Cancer Ther 1(1):23–35. doi:10.3816/SCT.2003.n.002 PubMedCrossRefGoogle Scholar
  5. 5.
    Bonadonna G, Valagussa P (1981) Dose-response effect of adjuvant chemotherapy in breast cancer. N Engl J Med 304(1):10–15PubMedCrossRefGoogle Scholar
  6. 6.
    Budman DR, Berry DA, Cirrincione CT, Henderson IC, Wood WC, Weiss RB, Ferree CR, Muss HB, Green MR, Norton L, Frei E 3rd (1998) Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The cancer and leukemia group B. J Natl Cancer Inst 90(16):1205–1211. doi:10.1093/jnci/90.16.1205 PubMedCrossRefGoogle Scholar
  7. 7.
    Chirivella I, Bermejo B, Insa A, Perez-Fidalgo A, Magro A, Rosello S, Garcia-Garre E, Martin P, Bosch A, Lluch A (2009) Optimal delivery of anthracycline-based chemotherapy in the adjuvant setting improves outcome of breast cancer patients. Breast Cancer Res Treat 114(3):479–484. doi:10.1007/s10549-008-0018-1 PubMedCrossRefGoogle Scholar
  8. 8.
    Michels SL, Barron RL, Reynolds MW, Smoyer Tomic K, Yu J, Lyman GH (2012) Costs associated with febrile neutropenia in the US. Pharmacoeconomics 30(9):809–823. doi:10.2165/11592980-000000000-00000 PubMedCrossRefGoogle Scholar
  9. 9.
    Trillet-Lenoir V, Green J, Manegold C, Von Pawel J, Gatzemeier U, Lebeau B, Depierre A, Johnson P, Decoster G, Tomita D et al (1993) Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer 29A(3):319–324PubMedCrossRefGoogle Scholar
  10. 10.
    Vogel CL, Wojtukiewicz MZ, Carroll RR, Tjulandin SA, Barajas-Figueroa LJ, Wiens BL, Neumann TA, Schwartzberg LS (2005) First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study. J Clin Oncol 23(6):1178–1184. doi:10.1200/JCO.2005.09.102 PubMedCrossRefGoogle Scholar
  11. 11.
    Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, Lyman GH, Pettengell R, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 47(1):8–32. doi:10.1016/j.ejca.2010.10.013 PubMedCrossRefGoogle Scholar
  12. 12.
    NCCN (2012) Myeloid growth factors. NCCN Clinical Practice Guidelines in Oncology v1.2012Google Scholar
  13. 13.
    Pettengell R, Bosly A, Szucs TD, Jackisch C, Leonard R, Paridaens R, Constenla M, Schwenkglenks M (2009) Multivariate analysis of febrile neutropenia occurrence in patients with non-Hodgkin lymphoma: data from the INC-EU prospective observational European neutropenia study. Br J Haematol 144(5):677–685. doi:10.1111/j.1365-2141.2008.07514.x PubMedCrossRefGoogle Scholar
  14. 14.
    Crawford J (2006) Risk assessment and guidelines for first-cycle colony-stimulating factor use in the management of chemotherapy-induced neutropenia. Oncology (Williston Park) 20(5 Suppl 4):22–28Google Scholar
  15. 15.
    Ellis GK, Livingston RB, Gralow JR, Green SJ, Thompson T (2002) Dose-dense anthracycline-based chemotherapy for node-positive breast cancer. J Clin Oncol 20(17):3637–3643PubMedCrossRefGoogle Scholar
  16. 16.
    Lyman GH, Lyman CH, Agboola O (2005) Risk models for predicting chemotherapy-induced neutropenia. Oncologist 10(6):427–437. doi:10.1634/theoncologist.10-6-427 PubMedCrossRefGoogle Scholar
  17. 17.
    von Minckwitz G, Schwenkglenks M, Skacel T, Lyman GH, Pousa AL, Bacon P, Easton V, Aapro MS (2009) Febrile neutropenia and related complications in breast cancer patients receiving pegfilgrastim primary prophylaxis versus current practice neutropaenia management: results from an integrated analysis. Eur J Cancer 45(4):608–617. doi:10.1016/j.ejca.2008.11.021 CrossRefGoogle Scholar
  18. 18.
    Crawford J, Glaspy JA, Stoller RG, Tomita DK, Vincent ME, McGuire BW, Ozer H (2005) Final results of a placebo-controlled study of filgrastim in small-cell lung cancer: exploration of risk factors for febrile neutropenia. Support Cancer Ther 3(1):36–46. doi:10.3816/SCT.2005.n.023 PubMedCrossRefGoogle Scholar
  19. 19.
    Hosmer W, Malin J, Wong M (2010) Development and validation of a prediction model for the risk of developing febrile neutropenia in the first cycle of chemotherapy among elderly patients with breast, lung, colorectal, and prostate cancer. Support Care Cancer. doi:10.1007/s00520-010-0821-1 PubMedGoogle Scholar
  20. 20.
    Schwenkglenks M, Pettengell R, Jackisch C, Paridaens R, Constenla M, Bosly A, Szucs TD, Leonard R (2011) Risk factors for chemotherapy-induced neutropenia occurrence in breast cancer patients: data from the INC-EU prospective observational European neutropenia study. Support Care Cancer 19(4):483–490. doi:10.1007/s00520-010-0840-y PubMedCrossRefGoogle Scholar
  21. 21.
    Koebnick C, Langer-Gould AM, Michael K, Gould MK, Chao CR, Iyer RL, Smith N, Wansu Chen W, Jacobsen SJ (2012) Sociodemographic characteristics of members of a large, integrated health care system: comparison with US Census Bureau data. Perm J 16(3):37–41PubMedGoogle Scholar
  22. 22.
    Glynn RJ, Schneeweiss S, Sturmer T (2006) Indications for propensity scores and review of their use in pharmacoepidemiology. Basic Clin Pharmacol Toxicol 98(3):253–259. doi:10.1111/j.1742-7843.2006.pto_293.x PubMedCrossRefGoogle Scholar
  23. 23.
    Ozer H (2003) New directions in the management of chemotherapy-induced neutropenia: risk models, special populations, and quality of life. Semin Oncol 30(4 Suppl 13):18–23PubMedCrossRefGoogle Scholar
  24. 24.
    Lyman GH, Morrison VA, Dale DC, Crawford J, Delgado DJ, Fridman M (2003) Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin’s lymphoma receiving CHOP chemotherapy. Leuk Lymphoma 44(12):2069–2076PubMedCrossRefGoogle Scholar
  25. 25.
    O’Reilly RA (1998) Splenomegaly in 2,505 patients in a large university medical center from 1913 to 1995. 1913 to 1962: 2,056 patients. West J Med 169(2):78–87PubMedGoogle Scholar
  26. 26.
    Wiseman BK, Doan CA (1942) A newly recognized granulopenic syndrome caused by excessive splenic leukolysis and successfully treated by splenectomy. Ann Intern Med 16:1097Google Scholar
  27. 27.
    Tomer Y, Davies TF (1993) Infection, thyroid disease, and autoimmunity. Endocr Rev 14(1):107–120PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Victoria M. Chia
    • 1
  • John H. Page
    • 1
  • Roberto Rodriguez
    • 2
  • Su-Jau Yang
    • 3
  • Julie Huynh
    • 2
    • 4
  • Chun Chao
    • 3
  1. 1.Center for Observational Research, Amgen Inc.Thousand OaksUSA
  2. 2.Department of OncologyLos Angeles Medical Center, Kaiser Permanente Southern CaliforniaLos AngelesUSA
  3. 3.Department of Research and EvaluationKaiser Permanente Southern CaliforniaPasadenaUSA
  4. 4.Department of Hematology and OncologyHarbor-UCLA Medical CenterTorranceUSA

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