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Risk factors for chemotherapy-induced neutropenia occurrence in breast cancer patients: data from the INC-EU Prospective Observational European Neutropenia Study

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Abstract

Background

Chemotherapy-induced neutropenia (CIN) places patients at risk of life-threatening infections. While reduction of chemotherapy dose or delay of the subsequent treatment cycle and, consequently, reduction of relative dose intensity (RDI) may limit myelotoxicity, these actions can also impact adversely on treatment outcome and should be avoided in adjuvant settings.

Patients and methods

Based on data from 444 breast cancer patients in the INC-EU Prospective Observational European Neutropenia Study, we have evaluated patient-specific and treatment-specific factors that impact on the incidence of grade 4 CIN (absolute neutrophil count <0.5 × 109/L), either during the first or in any cycle of (neo)adjuvant chemotherapy, across a range of regimens and doses.

Results

Using multivariate logistic regression analysis, risk factors for grade 4 CIN were identified as older age, lower weight, higher planned dose intensity of doxorubicin, epirubicin, or docetaxel, higher number of planned cycles, vascular comorbidity, lower baseline white blood cell count, and higher baseline bilirubin. Use of colony-stimulating factor before a neutropenic event occurred, dose delays, and dose reductions were protective against grade 4 CIN.

Conclusions

By identifying risk factors for grade 4 CIN, CSF prophylaxis may be appropriately targeted to prevent low RDI in patients treated with curative intent.

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Acknowledgements

The authors would like to thank the following physicians for providing patient data: J.C.A. Adansa; J.J.C. Hernandez; S. Al-Ismail; C. André; G.-A. Banat; A. Barnes; A.L. Barriuso; J.L. Bello; A. Biswas; A. Bols; A. Brownell; W. Brugger; R.O. Casasnovas; M. Clemens; R. Coleman; P. Colombat; N. Davidson; R. Depenbusch; H.G. Derigs; A. Engert; J.C. Espinosa; S. Ferrer; O. Fitoussi; B. Gaede; L. Garderet; B. Hancock; M. Hänel; A. Hasenburg; A. Hong; U. Karck; G. Köhler; A.W. Hutcheon; C. Lerchenmüller; R. Lipp; J.R.M. Lorenzo; K. McAdam; F. Majois; J.L. Mansi; M.G. Martinez; J. Mebis; N. Mounier; A.A. Munoz; A. O’Callaghan; M. Quigley; S. Rösel; C. Rudin; R. Schlag; G. Schlimok; M. Sandherr; P. Solal-Celigny; T. Steck; H. Tesch; D. Turner; X. Vallantin; J. Van Erps; E. Van Den Neste; A. Van Hoof; J.B. Vermorken; K. Verpoort; A. Wardley; M. Warm; E. Weidmann; J. Wimperis; W. Zeller. The authors wish to thank Prof. Gary Lyman, Duke University and the Duke Comprehensive Cancer Center, Durham, North Carolina and members of the Awareness of Neutropenia in Chemotherapy (ANC) Study Group for the useful discussions comparing risk models. The authors wish to thank Amgen (Europe) GmbH, Zug, Switzerland for supporting this work with an educational grant. The authors wish to thank medcept ltd., Switzerland, who provided medical writing support to the INC-EU with funding from Amgen (Europe) GmbH.

Conflicts of interest

This study was supported by an educational grant from Amgen (Europe) GmbH. M.S. receives research funding from Amgen and acts as a consultant in receipt of honoraria from Amgen. R.P. is a consultant in receipt of honoraria from Chugai, Bayer, Roche, and Amgen. C.J. is a consultant in receipt of honoraria from Amgen and Astra Zeneca. R.Pa. is a consultant in receipt of honoraria from Astra Zeneca, Novartis, Pfizer, Sanofis, and Schering-Plough and receives research funding from Amgen, Novartis, and Pfizer. M.C. has no conflicts of interest to declare. A.B. receives research funding from Amgen. T.S. has no conflicts of interest to declare. R.L. has modest share ownership interest in GlaxoSmithKline, is a consultant in receipt of honoraria from Amgen, Astra Zeneca, Novartis, Pfizer, Roche, and Zeneus, and was in receipt of research funding from Amgen.

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Authors and Affiliations

  1. European Center of Pharmaceutical Medicine, University of Basel, Klingelbergstrasse 61, 4056, Basel, Switzerland

    Matthias Schwenkglenks & Thomas D. Szucs

  2. Cellular and Molecular Medicine, St. George’s University of London, Cranmer Terrace, London, SW17 0RE, UK

    Ruth Pettengell

  3. Department of Gynecology and Obstetrics, Klinikum Offenbach, Starkenburgring 66, 63069, Offenbach, Germany

    Christian Jackisch

  4. Department of Medical Oncology, University Hospital Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium

    Robert Paridaens

  5. Servicio de Oncologia, Complexo Hospitalario de Pontevedra, 36071, Pontevedra, Spain

    Manuel Constenla

  6. Service d’Hématologie, Cliniques Universitaires UCL, Avenue Dr. Gaston Therasse, 5530, Godinne, Belgium

    André Bosly

  7. Cancer Services and Clinical Haematology, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK

    Robert Leonard

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  1. Matthias Schwenkglenks
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  2. Ruth Pettengell
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  3. Christian Jackisch
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  4. Robert Paridaens
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  5. Manuel Constenla
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  6. André Bosly
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  7. Thomas D. Szucs
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  8. Robert Leonard
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Correspondence to Matthias Schwenkglenks.

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Schwenkglenks, M., Pettengell, R., Jackisch, C. et al. 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, 483–490 (2011). https://doi.org/10.1007/s00520-010-0840-y

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  • DOI: https://doi.org/10.1007/s00520-010-0840-y

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