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

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Abstract

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.

Conclusions

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.

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Acknowledgment

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).

Author information

Authors and Affiliations

  1. Divisione di Oncologia e di Ematologia, Ospedale degli Infermi, and Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Azienda USL-Rimini Via Settembrini 2, I-47037, Rimini, Italy

    Lorenzo Gianni, Ilaria Panzini & Alberto Ravaioli

  2. IBCSG Statistical Center, Dana-Farber Cancer Institute, Boston, MA, USA

    Bernard F. Cole

  3. Dartmouth Medical School, Lebanon, NH, USA

    Bernard F. Cole

  4. St. Vincent’s Hospital Melbourne, Melbourne, Australia

    Raymond Snyder

  5. Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden

    Stig B. Holmberg

  6. Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

    Michael Byrne

  7. Centro di Riferimento Oncologico, Aviano, Italy

    Diana Crivellari

  8. European Institute of Oncology, Milan, Italy

    Marco Colleoni & Aron Goldhirsch

  9. Inselspital, Bern, Switzerland

    Stefan Aebi

  10. Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland

    Stefan Aebi & Olivia Pagani

  11. Oncologia Medica-Spedali Civili, Brescia, Italy

    Edda Simoncini

  12. Oncology Institute of Southern Switzerland, Bellinzona, Switzerland

    Olivia Pagani & Aron Goldhirsch

  13. International Breast Cancer Study Group Coordinating Center, Bern, Switzerland

    Monica Castiglione-Gertsch & Alan S. Coates

  14. IBCSG Statistical Center, Frontier Science and Technology Research Foundation, Boston, MA, USA

    Karen N. Price

  15. University of Sydney, Sydney, Australia

    Alan S. Coates

Authors
  1. Lorenzo Gianni
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  2. Bernard F. Cole
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  3. Ilaria Panzini
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  4. Raymond Snyder
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  5. Stig B. Holmberg
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  6. Michael Byrne
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  7. Diana Crivellari
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  8. Marco Colleoni
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  9. Stefan Aebi
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  10. Edda Simoncini
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  11. Olivia Pagani
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  12. Monica Castiglione-Gertsch
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  14. Aron Goldhirsch
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  15. Alan S. Coates
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  16. Alberto Ravaioli
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Corresponding author

Correspondence to Lorenzo Gianni.

IBCSG Trials 13-93 and 14-93 Participants and Authors

IBCSG Trials 13-93 and 14-93 Participants and Authors

Trial 13-93 Study Chair: Marco Colleoni; Trial 14-93 Study Chairs: Edda Simoncini, Olivia Pagani; Scientific Committee: A. Goldhirsch, A.S. Coates (Co-Chairs); Foundation Council: B. Thürlimann (President), M. Castiglione, A.S. Coates, J.P. Collins, H. Cortés Funes, R.D. Gelber, A. Goldhirsch, M. Green, A. Hiltbrunner, S.B. Holmberg, D. K. Hossfeld, I. Láng, J. Lindtner, C.-M. Rudenstam, R. Stahel, H.-J. Senn, A. Veronesi; Coordinating Center (Bern, Switzerland): M. Castiglione-Gertsch (CEO), A. Hiltbrunner (Director), G. Egli, M. Rabaglio, R. Studer, B. Ruepp, R. Maibach, M. Strausak, E. Marbot; Statistical Center (Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, MA, USA): R.D. Gelber (Group Statistician), K.N. Price (Director of Scientific Administration), B.F. Cole, S. Gelber, M.M. Regan, D. Zahrieh, Z. Sun, A. Giobbie-Hurder; Quality of Life Office (Bern, Switzerland): J. Bernhard, G. Egli, Ch. Hürny, D. Gerber; Pathology Office: B. Gusterson, G. Viale; Data Management Center (Frontier Science & Tech. Res. Found., Amherst, NY, USA): L. Blacher (Director), J. Celano, M. Isley, R. Hinkle, S. Lippert, K. Scott; Centro di Riferimento Oncologico Aviano, Italy: A. Veronesi, D. Crivellari, S. Monfardini, E. Galligioni, M.D. Magri, A. Buonadonna, S. Massarut, C. Rossi, E. Candiani, A. Carbone, R. Volpe, M. Roncadin, M. Arcicasa, F. Coran, S. Morassut; Spedali Civili & Fondazione Beretta, Brescia, Italy: E. Simoncini, G. Marini, P. Marpicati, M. Braga, P. Grigolato, L. Lucini; Istituto Europeo di Oncologia, Milano, Italy: A. Goldhirsch, M. Colleoni, G. Martinelli, G. Viale, L. Orlando, F. Nolè, R. Torrisi, T. De Pas, F. de Braud, S. Cinieri, F. Peccatori, A. Luini, R. Orecchia, G. Renne, F. de Braud, A. Costa, S. Zurrida, P. Veronesi, V. Sacchini, V. Galimberti, M. Intra, U. Veronesi; Ospedale Infermi Rimini, Italy: A. Ravaioli, D. Tassinari, G. Oliverio, F. Barbanti, P. Rinaldi, E. Pini, G. Drudi; Ospedale S. Eugenio Roma, Italy: M. Antimi, M. Minelli, V. Bellini, R. Porzio, E. Pernazza,G. Santeusanio, L.G. Spagnoli; General Hospital, Gorizia, Italy: S. Foladore, L. Foghin, G. Pamich, C. Bianchi, B. Marino, A. Murgia, V. Milan; West Swedish Breast Cancer Study Group, Göteborg, Sweden: C.M. Rudenstam, A. Wallgren, S. Ottosson-Lönn, R. Hultborn, G. Colldahl-Jädeström, E. Cahlin, J. Mattsson, S. B.Holmberg, O. Ruusvik, L.G. Niklasson, S. Dahlin, G. Karlsson, B. Lindberg, A. Sundbäck, S. BergegÂrdh, O. Groot, L.O. Dahlbäck, H. Salander, C. Andersson, M. Heideman, A. Nissborg, A. Wallin, G. Claes, T. Ramhult, J.H. Svensson, P. Liedberg, A. Nilsson, G. Havel, G. Oestberg, S. Persson, M. Suurküla, J. Matusik; The Institute of Oncology, Ljubljana, Slovenia: J. Lindtner, D. Erzen, T. Cufer, J. Cervek, O. Cerar, B. Zakotnik, E. Majdic, R. Golouh, J. Lamovec, J. Jancar, I. Vrhovec, M. Kramberger; Groote Schuur Hospital, Cape Town, Rep. of South Africa: E. Murray, I.D. Werner, D.M. Dent, A. Gudgeon, E. Panieri, E. McEvoy, J. Toop, R. Bowen; Sandton Oncology Center, Johannesburg, South Africa: D. Vorobiof, M. Chasen, G. Fotheringham, G. de Muelenaere, B. Skudowitz, C. Mohammed, A. Rosengarten; Madrid Breast Cancer Group, Madrid, Spain: H. Cortès-Funes, C. Mendiola, C. Gravalos, Colomer, M. Mendez, F. Cruz Vigo, P. Miranda, A. Sierra, F. Martinez-Tello, A. Garzon, S. Alonso, A. Ferrero, C. Vargas; SAKK (Swiss Group for Clinical Cancer Research): Inselspital, Bern: M.F. Fey, M. Castiglione-Gertsch, E. Dreher, H. Schneider, S. Aebi, K. Buser, J. Ludin, G. Beck, A. Haenel, J.M. Lüthi, H.J. Altermatt, M. Nandedkar; Kantonsspital, St. Gallen: H.J. Senn, B. Thürlimann, Ch. Oehlschlegel, G. Ries, M. Töpfer, U. Lorenz, A. Ehrsam, B. Späti, E. Vogel; Ospedale San Giovanni, Bellinzona: F. Cavalli, O. Pagani, H. Neuenschwander, L. Bronz, C. Sessa, M. Ghielmini, T. Rusca, P. Rey, J. Bernier, E. Pedrinis, T. Gyr, L. Leidi, G. Pastorelli, A. Goldhirsch; Kantonsspital, Basel: R. Herrmann, C.F. Rochlitz, J.F. Harder, O. Köchli, U. Eppenberger, J. Torhorst; Hôpital des Cadolles, Neuchâtel: D. Piguet, P. Siegenthaler, V. Barrelet, R.P. Baumann; Kantonsspital, Zürich: B. Pestalozzi, C. Sauter, V. Engeler, U. Haller, U. Metzger, P. Huguenin, R. Caduff; Centre Hôpitalier Universitaire, Lausanne: L. Perey, S. Leyvraz, P. Anani, C. Genton, F. Gomez, P. De Grandi, P. Reymond, R. Mirimanoff, M. Gillet, J.F. Delaloye; Hôpital Cantonal, Geneva: P. Alberto, H. Bonnefoi, P. Schäfer, F. Krauer, M. Forni, M. Aapro, R. Egeli, R. Megevand, E. Jacot-des-Combes, A. Schindler, B. Borisch, S. Diebold; Kantonsspital Graubünden, Chur: F. Egli, P. Forrer, A. Willi, R. Steiner. J. Allemann, T. Rüedi, A. Leutenegger, U. Dalla Torre; Kantonsspital Aarau: A. Schönenberger, M. Wernli, M. Bargetzi, W. Mingrone, P. Schmid, E. Bärtschi, K. Beretta; Australian New Zealand Breast Cancer Trials Group (ANZ BCTG): J.F. Forbes, D. Lindsay, A. Wilson, D. Preece; Statistical Center, NHMRC CTC, University of Sydney: R.J. Simes, H. Dhillon; The Cancer Council Victoria, Melbourne, VIC: J. Collins, R. Snyder, E. Abdi, R. Abraham, R. Basser, P. Briggs, W.I. Burns, M. Chipman, J. Chirgwin, V. Ganju, G. Goss, M. Green, I. Haines, S. Hart, R. Holmes, G. Lindeman, J. McKendrick, S. McLachlan, R. McLennan, P. Mitchell, G. Richardson, M. Schwarz, C. Underhill; The Canberra Hospital, Canberra, ACT: R. Stuart-Harris; Flinders Medical Centre, Bedford Park, SA: T. Malden; Newcastle Mater Misericordiae Hospital, Waratah, NSW: J.F. Forbes, J. Stewart, S. Ackland, A. Bonaventura, D. Jackson; Mount Hospital, Perth, WA: G. van Hazel; Prince of Wales Hospital, Randwick, NSW: M. Friedlander, B. Brigham, C. Lewis; Royal Perth Hospital, Perth, WA: E. Bayliss, A. Chan, D. Ransom, J. Trotter; Sir Charles Gairdner Hospital, Nedlands, WA: M. Byrne, G. van Hazel, A. Davidson, J. Dewar, M. Buck; Royal Prince Alfred Hospital and Dubbo Base Hospital Sydney, NSW: J. Beith, M. Boyer, A.S. Coates, R. J. Simes, A. Sullivan, M.H.N. Tattersall; St George Hospital. Kogarah, NSW: P. de Souza; Auckland Hospital, Auckland, New Zealand: V.J. Harvey, P. Thompson, D. Porter

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Gianni, L., Cole, B.F., Panzini, I. et al. Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group. Support Care Cancer 16, 67–74 (2008). https://doi.org/10.1007/s00520-007-0295-y

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  • DOI: https://doi.org/10.1007/s00520-007-0295-y

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