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Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study

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Abstract

The adjuvant use of aromatase inhibitors in breast cancer is associated with adverse effects on bone health. We previously reported a decline in bone mineral density (BMD) following the switch from tamoxifen to exemestane in the Intergroup Exemestane Study (IES). Here we report effects of endocrine treatment withdrawal on BMD, bone turnover markers (BTM) and fracture rates. 4,724 patients took part in IES, and 206 patients were included in a bone sub-study. BMD and BTM were assessed pre-randomization, during and after the end of treatment (EOT). To evaluate treatment withdrawal effects, 12- and 24-month post EOT BMD results are available for 122 and 126 patients, respectively. Similar patient numbers had BTM measured post EOT. Following treatment withdrawal, the differences in BMD observed between the two endocrine strategies were partially reversed. At 24 months from EOT, spine BMD increased by 1.53% (95%CI 0.63–2.43; p = 0.001) after stopping exemestane and fell by 1.93% (95%CI −2.91 to 0.95; p = 0.0002) following tamoxifen withdrawal. A similar pattern of changes was observed at the hip. At 2 years post EOT, BMD changes from baseline were similar with both treatment strategies. Corresponding inverse changes in BTM were seen, with an increase following tamoxifen withdrawal and a reduction after exemestane. A higher number of fractures occured during exemestane treatment, but fracture rates were similar after treatment withdrawal. With the switch strategy used in IES, the on treatment adverse bone effects of exemestane are reversed. Ongoing monitoring of BMD is therefore not routinely required.

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Acknowledgments

We would like to thank the following investigators who also contributed patients to this study. J Chirgwin, Box Hill Hospital and Maroondah Hospital, Victoria, Australia; L Petruzelka, University Hospital, Prague, Czech Republic; P Redmond, Cork University Hospital, Cork, Ireland; A Hill, St. Vincent’s Hospital, Dublin, Ireland; V Harvey, Auckland Hospital, Auckland, New Zealand; M Krzakowski, Centrum Onkologii, Warszawa, Poland; P Tomczak, Klinika Onkologii Akademii Medycznej W Poznaniu, Poznan, Poland; P Simmonds, Southampton General Hospital, Southampton, UK; S Goodman, Yeovil District Hospital, Somerset, UK; AU Buzdar, University of Texas M. D. Anderson Cancer Center, Houston, USA. We would also like to thank Jazz Heer, Suzanne Hodgson, Joy Liao, Deirdre Price (Central Evaluation Facility), George Baffoe, Saro Niththyananthan (Bone Markers Unit) and Iva Amoako, Claire Snowdon, Sandy Beare, Lorna Gibson (Coordinating Data Centre) of Imperial College London, UK; Pfizer for their continued support and funding; the Independent Data Monitoring Committee (IDMC); and especially, the women who participated in this study.

Conflict of interest

R. E. Coleman: Honoraria—Pfizer.

L. M. Banks: Research Funding—Pfizer.

S. I. Girgis: None.

E. Vrdoljak: Honoraria—Pfizer.

J. Fox: None.

S. J. Cawthorn: None.

R. C. Coombes: Honoraria—Pfizer, Research Funding—Pfizer.

A. Patel: Honoraria—Pfizer, Research Funding—Pfizer.

J. M. Bliss: Honoraria—Pfizer, Research Funding—Pfizer.

L. S. Kilburn: None.

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Authors and Affiliations

  1. Academic Unit of Clinical Oncology, Cancer Research Centre, Weston Park Hospital, Sheffield, UK

    Robert E. Coleman

  2. Department of Biosurgery and Surgical Technology, Imperial College, London, UK

    Linda M. Banks

  3. Department of Investigative Medicine, Imperial College, London, UK

    Samia I. Girgis

  4. Center of Oncology, Clinical Hospital Split, Split, Croatia

    Eduard Vrdoljak

  5. Castle Hill Hospital, Cottingham, Hull, UK

    John Fox

  6. Frenchay Hospital, Bristol, UK

    Simon J. Cawthorn

  7. St Margaret’s Hospital, Epping, UK

    Ashraf Patel

  8. Section of Clinical Trials, The Institute of Cancer Research, Sutton, UK

    Judith M. Bliss & Lucy S. Kilburn

  9. ICCG Data Centre, Imperial College, London, UK

    R. Charles Coombes

Authors
  1. Robert E. Coleman
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  2. Linda M. Banks
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  3. Samia I. Girgis
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  4. Eduard Vrdoljak
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  5. John Fox
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  6. Simon J. Cawthorn
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  7. Ashraf Patel
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  8. Judith M. Bliss
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  9. R. Charles Coombes
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  10. Lucy S. Kilburn
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Corresponding author

Correspondence to Robert E. Coleman.

Additional information

This study was conducted on behalf of the Intergroup Exemestane Study (IES) group.

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Coleman, R.E., Banks, L.M., Girgis, S.I. et al. Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study. Breast Cancer Res Treat 124, 153–161 (2010). https://doi.org/10.1007/s10549-010-1121-7

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  • DOI: https://doi.org/10.1007/s10549-010-1121-7

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