Commentary

The large, randomised MORE trial by Johnell et al previously reported reduction in vertebral fracture risk and breast cancer risk by raloxifene in a group of women selected on the basis of having low bone mineral density or pre-existing vertebral fracture, or both. This new study determined whether self reported prior menopausal HT influenced raloxifene’s ability to prevent vertebral fractures or to reduce breast cancer risk.

This analysis was not preplanned; thus, it is not surprising that women who used HT before participating in MORE had different characteristics from those who had not. Women who had prior HT use had a lower baseline bone density than women who had no prior HT use. The authors posit that baseline differences, such as residual protective effects of oestrogen, may explain the differential reduction in vertebral fracture risk by raloxifene between women who had prior HT use and those who had not.

The other major finding of this study was that breast cancer risk was reduced to a comparable extent in women who had and had not taken HT. No formal breast cancer risk assessment was done at the initiation of the MORE trial. Thus, subgroup analysis of high risk women was not possible.

Many questions remain. Even if raloxifene receives US Food and Drug Administration approval for breast cancer risk reduction in the future, head to head trials comparing efficacy and adverse effects of raloxifene, tamoxifen, and aromatase inhibitors are not yet available. Moreover, many women who discontinue oestrogen therapy will choose bisphosphonates instead of raloxifene because raloxifene has not been shown to reduce hip fracture risk. Until completion of pending studies (such as the Study of Tamoxifen and Raloxifene [STAR] trial comparing tamoxifen and raloxifene for preventing breast cancer),¹ tamoxifen will remain the choice for breast cancer risk reduction and bisphosphonates will remain the treatment of choice to prevent hip fractures in women with osteoporosis.