New endocrine therapies for breast cancer.

Abstract

How do the new endocrine therapies stand up to the aims of modern endocrine therapy outlined in Table 1? We wish to see increased efficacy, decreased toxicity and improved general health in women taking a new agent. None of the new non-steroidal anti-oestrogens have shown unequivocal evidence of improved efficacy in the clinic to mirror their improved profiles over tamoxifen in preclinical studies. We know that toremifene is equivalent to tamoxifen, but we do not have any phase III data from the other four compounds in development. The specific steroidal antioestrogen, ICI 182,780, looks very promising, but is early in its developmental programme. The new aromatase inhibitors are likely to prove equal to tamoxifen or progestagens, but it is disappointing that improved oestrogen suppression has not led, to date, to improved efficacy. No comment can be made about adjuvant or preventative therapy for any of the new agents, although trials are planned for the new aromatase inhibitors in this clinical situation. Currently, the antiprogestins are disappointing and we will need to wait a considerable time for new agents in preclinical testing to reach the clinic. Many of the new agents are associated with decreased toxicity. It is likely that the NSAEs will be equitoxic with tamoxifen. The steroidal antioestrogen looks particularly non-toxic as do the new aromatase inhibitors, and thus we have an advance in terms of reduced toxicity. The effects of the new agents on the uterus, lipids and bone are in the early stages of testing. Raloxifene, ICI 182,780 and the new aromatase inhibitors are expected to have no proliferative effects on the endometrium, but only the new NSAEs are expected to have beneficial cardiovascular and skeletal effects. If the steroidal anti-oestrogens and new aromatase inhibitors become adjuvant therapies of choice, other agents to prevent osteoporosis and cardiovascular events may also have to be administered.