Steroid hormones play an important role in growth regulation of both normal breast tissue and breast tumours. The question remains which steroids are involved and how they act in the development and progression of breast cancer. It is hoped tlhat a fundamental understanding of the mechanisms involved in effects of steroids on cell growth will provide a baisis for improvement in therapy. Figure 1 illustrates the stages in the development of breast cancer. Steroids may play a permissive role in carcinogenesis, which remains poorly understood, but by contrast they play an important part in regulation of the tumour cells and progression of the disease. Of all the steroids, oestrogen has undoubtedly received the greatest attention (Beck, 1989). It is nearly a century since Beatson (1896) discovered the beneficial effect of ovariectomy in some patients with metastatic breast cancer and the role of oestrogen in tumourcell growth remains today the one clue to providing a therapy not based solely on general cytotoxic drugs. Recent data suggest, however, that proliferation of normal breast epithelial cells may be regulated by progestins rather than by oestrogen (Anderson et al., 1989) and that progestins could have adverse effects on early stages of breast cancer (King, 1990)i. These facts could imply a switch from progestin to oestrogen regulation of cell growth at some stage during the early development of breast cancer. Later stages of progression, however, are characterized by a loss of any steroid hormone sensitivity, and this presents a major current clinical problem. Thirty percent of established human breast cancers regress under endocrine therapy, but regression is invariably of a temporary nature to be replaced ultiimately by steroid-independent tumours. Our general aims, therefore, should be to understand growth regulation of normal breast epithelial cells, how such cells become malignant often responding initially to oestrogen, and then why the cells should subsequently develop steroid independence and resistance to endocrine therapy.
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