Raloxifene: handle with care

We have seen some women at high risk for breast cancer taking the selective estrogen receptor modulator raloxifene, in the belief that it is a breast cancer “preventive” with few of the risks or side effects of tamoxifen. Raloxifene is, in fact, not approved in North America for breast cancer prevention. Furthermore, perhaps because raloxifene has become available more recently, women, and sometimes physicians, do not seem to be aware that the risks of developing deep venous thrombosis, pulmonary emboli and hot flashes are similar to those seen with tamoxifen.1

We have also observed the frequent use of raloxifene by women who have completed the recommended 5-year course of adjuvant therapy with tamoxifen following a diagnosis of breast cancer. In randomized trials, there were more recurrences of breast cancer and more deaths in women who received adjuvant therapy with tamoxifen for 10 or more years than in those who received tamoxifen for 5 years.2 This may be explained by the observation in animal and in vitro models that cells grown for long periods in the presence of tamoxifen can become dependent on it.3

Because raloxifene is very similar to tamoxifen, the prescription of raloxifene to a patient with residual tamoxifen- dependent breast cancer cells could promote the growth of such a cancer. In fact, it has recently been demonstrated in animal models that tamoxifen- dependent breast cancer cells can be stimulated by raloxifene.4 Thus, physicians should be particularly concerned about the prescription of raloxifene in this situation.

If patients can develop tamoxifen- dependent breast cancers after protracted periods of therapy, perhaps women with a previous diagnosis of breast cancer who have not been treated with tamoxifen but who are treated with raloxifene for osteoporosis may develop raloxifene-dependent tumours. There are few safety data on the use of raloxifene in women with a previous diagnosis of breast cancer.5^,6

In summary, raloxifene is not currently indicated for breast cancer prevention; it should not be prescribed as a substitute for tamoxifen as adjuvant therapy for breast cancer; it should not be prescribed to women who have completed 5 years of tamoxifen as adjuvant therapy for breast cancer; and the prescription of raloxifene to prevent or treat osteoporosis in women with a previous history of breast cancer who have not received tamoxifen or who have received it for less than 5 years should be considered only with caution and after discussion with the patient's medical oncologist. Alternative approaches to treat or prevent osteoporosis in women with a previous diagnosis of breast cancer include therapy with bisphosphonates, calcitonin and calcium supplements, diet modifications and exercise.