Anti-Estrogens

Types of breast cancers

The majority of breast cancers are estrogen receptor positive (ER) and grow in response to estrogen, although a large number of these tumours are also progesterone receptor positive (ER/PR) and grow in response to progesterone.  Breast tumours that are only estrogen dependent respond well to anti-estrogen treatment which is usually started after surgery and chemotherapy/ radiotherapy.

Another form of breast cancer is responsive to Human Epidermal Growth Factor a protein that stimulates cell growth through a specific receptor (HER-2).  These tumours have more than usual numbers of receptors for HER-2 receptors and tend to be more aggressive and fast growing.  They do not respond to anti-estrogen therapy, although they do respond to another form of therapy that makes use of monoclonal antibodies to target and kill the cancer cells.  

Anti-estogen therapy

Anti-estrogen therapy is used to treat estrogen-dependent breast cancers to prevent their growth and recurrence.  There are two types of anti-estrogen therapy available and they work by different modes of action to reduce the stimulation of the cancer cells by estrogen.

• Selective oestrogen receptor modulator (SERM):  These drugs, such as tamoxifen, block the oestrogen receptor on tumour cells by binding to the receptor but do not mimic the action of estrogen on these cells.  This action prevents the binding of estrogen to its receptor and prevents the growth of early and advanced stage tumours and also helps prevent their recurrence. SERMS do however mimic the action of estrogens on other cells, such as bone cells and can be used to help prevent osteoporosis in post-menopausal women.
• Aromatase inhibitor:  These drugs, such as anastrozole and letrozole, block biosynthesis of oestrogen by inhibiting the action of the enzyme aromatase, which is a critical enzyme in the biosynthesis of estrogen from its precursors, particularly androstenedione, in peripheral tissues such as adipose and breast.¹  Estrone produced by the action of aromatase is then converted to estadiol, which is the more active form of estrogen and binds to the estrogen receptor in breast tumours.  These drugs and can only be used in post-menopausal women, who have stops producing estrogen naturally. 

References

1. Reed MJ.  The role of aromatase in breast tumors.  Breast Cancer Research and Treatment. 1994: 30; 7-17.