Supportive Care in Cancer

, Volume 16, Issue 1, pp 67–74 | Cite as

Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group

  • Lorenzo GianniEmail author
  • Bernard F. Cole
  • Ilaria Panzini
  • Raymond Snyder
  • Stig B. Holmberg
  • Michael Byrne
  • Diana Crivellari
  • Marco Colleoni
  • Stefan Aebi
  • Edda Simoncini
  • Olivia Pagani
  • Monica Castiglione-Gertsch
  • Karen N. Price
  • Aron Goldhirsch
  • Alan S. Coates
  • Alberto Ravaioli
Original Article


Goal of the work

Anemia is a common side effect of chemotherapy. Limited information exists about its incidence and risk factors. The objective of this study was to evaluate the incidence of anemia and risk factors for anemia occurrence in patients with early breast cancer who received adjuvant chemotherapy.

Materials and methods

We evaluated risk factors for anemia in pre- and post/perimenopausal patients with lymph node-positive early breast cancer treated with adjuvant chemotherapy in two randomized trials. All patients received four cycles of doxorubicin and cyclophosphamide (AC) followed by three cycles of cyclophosphamide, methotrexate, fluorouracil (CMF). Anemia incidence was related to baseline risk factors. Multivariable analysis used logistic and Cox regression.

Main results

Among the 2,215 available patients, anemia was recorded in 11% during adjuvant chemotherapy. Grade 2 and 3 anemia occurred in 4 and 1% of patients, respectively. Pretreatment hemoglobin and white blood cells (WBC) were significant predictors of anemia. Adjusted odds ratios (logistic regression) comparing highest versus lowest quartiles were 0.18 (P < 0.0001) for hemoglobin and 0.52 (P = 0.0045) for WBC. Age, surgery type, platelets, body mass index, and length of time from surgery to chemotherapy were not significant predictors. Cox regression results looking at time to anemia were similar.


Moderate or severe anemia is rare among patients treated with AC followed by CMF. Low baseline hemoglobin and WBC are associated with a higher risk of anemia.


Adjuvant therapy Adverse event Anemia Breast cancer Chemotherapy 



We thank the patients, physicians, nurses, data managers, and trial coordinators who participate in the International Breast Cancer Study Group trials and Joie Celano for central data management. Supported in part by the Swiss Group for Clinical Cancer Research, Frontier Science and Technology Research Foundation, The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group, National Health and Medical Research Council of Australia (grants 940892, 980380, 100925), United States National Cancer Institute (CA-75362), Swedish Cancer Society, Foundation for Clinical Research of Eastern Switzerland, Cancer Association of South Africa (for South African patients), Orion-Farmos (for medication for trial 14–93).


  1. 1.
    Barrett-Lee PJ, Ludwig H, Birgegard G, Bokemeyer C, Gascon P, Kosmidis PA, Krzakowski M, Nortier JW, Kongable G, Schneider M, Schrijvers D, Van Belle SJ (2006) European cancer anaemia survey advisory board and participating centers. Independent risk factors for anemia in cancer patients receiving chemotherapy: results from the European Cancer Anaemia Survey. Oncology 70:34–48PubMedCrossRefGoogle Scholar
  2. 2.
    Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock J, Trelle S, Weingart O, Bayliss S, Djulbegovic B, Bennett CL, Langensiepen S, Hyde C, Engert A (2006) Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst 98:708–714PubMedCrossRefGoogle Scholar
  3. 3.
    Bron D, Meuleman N, Mascaux C (2001) Biological basis of anemia. Semin Oncol 28(suppl 8):S1–S6CrossRefGoogle Scholar
  4. 4.
    Cella D (1998) Factors influencing quality of life in cancer patients: anemia and fatigue. Semin Oncol 25(suppl 7):S43–S46Google Scholar
  5. 5.
    Chang J, Couture F, Young S, McWatters KL, Lau CY (2005) Weekly epoetin alfa maintains hemoglobin, improves quality of life, and reduces transfusion in breast cancer patients receiving chemotherapy. J Clin Oncol 23:2597–2605PubMedCrossRefGoogle Scholar
  6. 6.
    Coiffier B, Guastalla JP, Pujade-Lauraine E, Bastit P (2001) Anemia Study Group Anemia Study Group. Predicting cancer-associated anaemia in patients receiving non-platinum chemotherapy: results of a retrospective survey. Eur J Cancer 37:1617–1623PubMedCrossRefGoogle Scholar
  7. 7.
    Couture F, Turner AR, Melosky B, Xiu L, Plante RK, Lau CY, Quirt I (2005) Prior red blood cell transfusions in cancer patients increase the risk of subsequent transfusions with or without recombinant human erythropoietin management. Oncologist 10:63–71PubMedCrossRefGoogle Scholar
  8. 8.
    Demetri GD, Kris M, Wade J, Degos L, Cella D (1998) Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: results from a prospective community oncology study. Procrit Study Group. J Clin Oncol 16:3412–3425PubMedGoogle Scholar
  9. 9.
    Denison U, Baumann J, Peters-Engl C, Samonigg H, Krippl P, Lang A, Obermair A, Wagner H, Sevelda P (2003) Incidence of anaemia in breast cancer patients receiving adjuvant chemotherapy. Breast Cancer Res Treat 79:347–353PubMedCrossRefGoogle Scholar
  10. 10.
    Dranitsaris G, Clemons M, Verma S, Lau C, Vincent M (2005) Chemotherapy-induced anaemia during adjuvant treatment for breast cancer: development of a prediction model. Lancet Oncol 6:856–863PubMedCrossRefGoogle Scholar
  11. 11.
    Du XL, Osborne C, Goodwin JS (2002) Population-based assessment of hospitalizations for toxicity from chemotherapy in older women with breast cancer. J Clin Oncol 20:4636–4642PubMedCrossRefGoogle Scholar
  12. 12.
    Groopman JE, Itri LM (1999) Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst 91:1616–1634PubMedCrossRefGoogle Scholar
  13. 13.
    Hardee ME, Arcasoy MO, Blackwell KL, Kirkpatrick JP, Dewhirst MW (2006) Erythropoietin biology in cancer. Clin Cancer Res 12:332–339PubMedCrossRefGoogle Scholar
  14. 14.
    Hassett MJ, O’Malley AJ, Pakes JR, Newhouse JP, Earle CC (2006) Frequency and cost of chemotherapy-related serious adverse effects in a population sample of women with breast cancer. J Natl Cancer Inst 98:1108–1117PubMedCrossRefGoogle Scholar
  15. 15.
    Henke M, Mattern D, Pepe M, Bezay C, Weissenberger C, Werner M, Pajonk F (2006) Do erythropoietin receptors on cancer cells explain unexpected clinical findings? J Clin Oncol 24:4708–4713PubMedCrossRefGoogle Scholar
  16. 16.
    International Breast Cancer Study Group (2004) Toremifene and tamoxifen are equally effective for early-stage breast cancer: first results of International Breast Cancer Study Group Trials 12-93 and 14-93. Ann Oncol 15:1749–1759CrossRefGoogle Scholar
  17. 17.
    International Breast Cancer Study Group (2006) Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13–93. J Clin Oncol 24:1332–1341CrossRefGoogle Scholar
  18. 18.
    Kirshner J, Hatch M, Hennessy DD, Fridman M, Tannous RE (2004) Anemia in stage II and III breast cancer patients treated with adjuvant doxorubicin and cyclophosphamide chemotherapy. Oncologist 9:25–32PubMedCrossRefGoogle Scholar
  19. 19.
    Leyland-Jones B, Semiglazov V, Pawlicki M, Pienkowski T, Tjulandin S, Manikhas G, Makhson A, Roth A, Dodwell D, Baselga J, Biakhov M, Valuckas K, Voznyi E, Liu X, Vercammen E (2005) Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol 23:5960–5972PubMedCrossRefGoogle Scholar
  20. 20.
    Littlewood TJ, Zagari M, Pallister C, Perkins A (2003) Baseline and early treatment factors are not clinically useful for predicting individual response to erythropoietin in anemic cancer patients. Oncologist 8:99–107PubMedCrossRefGoogle Scholar
  21. 21.
    National Cancer Institute. Cancer Therapy Evaluation Program: Common Terminology Criteria for Adverse Events v3.0 (CTCAE), 8/2006 update.
  22. 22.
    National Comprehensive Cancer Network. National Comprehensive Cancer Network: clinical practice guidelines in oncology: senior adult oncology-Version 1.2005.
  23. 23.
    Pivot X, Guardiola E, Etienne M, Thyss A, Foa C, Otto J, Schneider M, Magne N, Bensadoun RJ, Renee N, Milano G (2000) An analysis of potential factors allowing an individual prediction of cisplatin-induced anaemia. Eur J Cancer 36:852–857PubMedCrossRefGoogle Scholar
  24. 24.
    Ray-Coquard I, Le Cesne A, Rubio MT, Mermet J, Maugard C, Ravaud A, Chevreau C, Sebban C, Bachelot T, Biron P, Blay JY (1999) Risk model for severe anemia requiring red blood cell transfusion after cytotoxic conventional chemotherapy regimens. The Elypse 1 Study Group. J Clin Oncol 17:2840–2846PubMedGoogle Scholar
  25. 25.
    Tanvetyanon T, Choudhury AM (2006) Severity, risk factors, and physician practices in the management of anemia during concurrent chemoradiation for head and neck carcinoma. Cancer 106:1554–1559PubMedCrossRefGoogle Scholar
  26. 26.
    Tas F, Eralp Y, Basaran M, Sakar B, Alici S, Argon A, Bulutlar G, Camlica H, Aydiner A, Topuz E (2002) Anemia in oncology practice: relation to diseases and their therapies. Am J Clin Oncol 25:371–379PubMedCrossRefGoogle Scholar
  27. 27.
    Vincent M, Dranitsaris G, Verma S, Lau C, Gascon P, Van Belle S, Ludwig H (2007) The development and validation of a prediction tool for chemotherapy-induced anemia in patients with advanced nonsmall cell lung cancer receiving palliative chemotherapy. Support Care Cancer 15(3):265–272PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Lorenzo Gianni
    • 1
    Email author
  • Bernard F. Cole
    • 2
    • 3
  • Ilaria Panzini
    • 1
  • Raymond Snyder
    • 4
  • Stig B. Holmberg
    • 5
  • Michael Byrne
    • 6
  • Diana Crivellari
    • 7
  • Marco Colleoni
    • 8
  • Stefan Aebi
    • 9
    • 10
  • Edda Simoncini
    • 11
  • Olivia Pagani
    • 10
    • 12
  • Monica Castiglione-Gertsch
    • 13
  • Karen N. Price
    • 14
  • Aron Goldhirsch
    • 8
    • 12
  • Alan S. Coates
    • 13
    • 15
  • Alberto Ravaioli
    • 1
  1. 1.Divisione di Oncologia e di EmatologiaOspedale degli Infermi, and Istituto Scientifico Romagnolo per lo Studio e la Cura dei TumoriRiminiItaly
  2. 2.IBCSG Statistical CenterBostonUSA
  3. 3.Dartmouth Medical SchoolLebanonUSA
  4. 4.St. Vincent’s Hospital MelbourneMelbourneAustralia
  5. 5.Department of SurgerySahlgrenska University HospitalGothenburgSweden
  6. 6.Sir Charles Gairdner HospitalNedlandsAustralia
  7. 7.Centro di Riferimento OncologicoAvianoItaly
  8. 8.European Institute of OncologyMilanItaly
  9. 9.InselspitalBernSwitzerland
  10. 10.Swiss Group for Clinical Cancer Research (SAKK)BernSwitzerland
  11. 11.Oncologia Medica-Spedali CiviliBresciaItaly
  12. 12.Oncology Institute of Southern SwitzerlandBellinzonaSwitzerland
  13. 13.International Breast Cancer Study Group Coordinating CenterBernSwitzerland
  14. 14.IBCSG Statistical CenterFrontier Science and Technology Research FoundationBostonUSA
  15. 15.University of SydneySydneyAustralia

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