Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane
Study.
Author(s): Coleman RE, Banks LM, Girgis SI, Vrdoljak E, Fox J, Cawthorn SJ, Patel A, Bliss
JM, Coombes RC, Kilburn LS.
Affiliation(s): Academic Unit of Clinical Oncology, Cancer Research Centre, Weston Park Hospital,
Sheffield, UK. R.E.Coleman@sheffield.ac.uk
Publication date & source: 2010, Breast Cancer Res Treat. , 124(1):153-61
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 occurred 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.
|