Progestins and antiprogestins in mammary tumour growth and metastasis

Growth of the normal mammary gland involves proliferation, differentiation, programmed cell death and remodelling of the basement membrane throughout the cyclic ovarian stimulation of the menstrual cycle and the pregnancy/lactation cycle. The regulation of these processes involves a balance between the actions of oestrogen and progesterone. Although it is generally accepted that oestrogens are the major adverse hormonal factor in onset and progression of human breast cancer, recent studies suggest that progesterone and its synthetic progestins may be more important than oestrogen as an ovarian stimulus in driving proliferation of normal human and rodent mammary epithelium. One might expect that some aspects of these complex progestin-regulated events might be retained in breast cancer. This review focuses on evidence that progesterone has proliferative actions in breast cancers; on the role of progestins in regulation of metastasis-related adhesion molecules on breast cancer cells and on the preliminary data showing that progesterone antagonists may be powerful new tools for the management of metastastic breast cancer. This evidence suggests that progesterone is a stimulus for onset and progression of breast tumours and that antiprogestins can interrupt these processes.