Tamoxifen Adjuvant breast cancer treatments associated with bone loss
Tamoxifen is probably the most widely used endocrine treatment for breast cancer worldwide. It is only effective in women with ER+ breast cancer, and most patients with these cancers will receive the drug at some time. Until recently, it was the gold standard for the adjuvant endocrine treatment of patients with ER+ operable breast cancer. In spite of high levels of circulating oestrogen from the ovaries in premenopausal women, compared with relatively low levels from non-ovarian tissue in postmenopausal women, the anticancer response to tamoxifen in pre and postmenopausal women with metastases is similar.
Tamoxifen is an oestrogen antagonist that competitively inhibits oestrogen binding to the oestrogen receptor. However, tamoxifen may become a tumour agonist, thereby reducing or
reversing its antiproliferative activity. With respect to bone, tamoxifen has a differential effect in pre and postmenopausal women. In premenopausal women with high levels of circulating oestrogen from the ovaries, tamoxifen predominantly has an anti-oestrogenic effect causing increased loss of BMD for 1–2 years. However, this loss is only about 1–2% and is not persistent through 5 years of tamoxifen therapy. No special monitoring or treatment to prevent this loss would be required. In postmenopausal women, tamoxifen is known to increase BMD of the spine, hip, but not the forearm51-53 or total body.46 It also reduces biochemical markers
of bone resorption and bone formation to a similar extent to raloxifene.
In summary, the bone loss caused by tamoxifen in premenopausal women does not present a clinical problem requiring boneprotecting medication, and tamoxifen protects against bone loss in postmenopausal women. However, following ovarian suppression with luteinizing hormone-releasing hormone analogues, the oestrogen agonist action of tamoxifen is insufficient to counteract the rapid bone loss associated with medical castration.
Tamoxifen is probably the most widely used endocrine treatment for breast cancer worldwide. It is only effective in women with ER+ breast cancer, and most patients with these cancers will receive the drug at some time. Until recently, it was the gold standard for the adjuvant endocrine treatment of patients with ER+ operable breast cancer. In spite of high levels of circulating oestrogen from the ovaries in premenopausal women, compared with relatively low levels from non-ovarian tissue in postmenopausal women, the anticancer response to tamoxifen in pre and postmenopausal women with metastases is similar.
Tamoxifen is an oestrogen antagonist that competitively inhibits oestrogen binding to the oestrogen receptor. However, tamoxifen may become a tumour agonist, thereby reducing or
reversing its antiproliferative activity. With respect to bone, tamoxifen has a differential effect in pre and postmenopausal women. In premenopausal women with high levels of circulating oestrogen from the ovaries, tamoxifen predominantly has an anti-oestrogenic effect causing increased loss of BMD for 1–2 years. However, this loss is only about 1–2% and is not persistent through 5 years of tamoxifen therapy. No special monitoring or treatment to prevent this loss would be required. In postmenopausal women, tamoxifen is known to increase BMD of the spine, hip, but not the forearm51-53 or total body.46 It also reduces biochemical markers
of bone resorption and bone formation to a similar extent to raloxifene.
In summary, the bone loss caused by tamoxifen in premenopausal women does not present a clinical problem requiring boneprotecting medication, and tamoxifen protects against bone loss in postmenopausal women. However, following ovarian suppression with luteinizing hormone-releasing hormone analogues, the oestrogen agonist action of tamoxifen is insufficient to counteract the rapid bone loss associated with medical castration.
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