Aromatase inhibitors and breast cancer.
Oestrogens are involved in risk to, and progression of, breast cancer. Drugs that inhibit the production of oestrogens (aromatase inhibitors, AIs), are therefore extremely attractive strategies both to prevent the disease and to treat established tumours. AIs now have a central role in the treatment of established breast cancer and are being considered for prevention. Third generation agents have been derived from rational drug design. They are able to block oestrogen production and reduce oestrogen levels to a degree that has not been observed previously and without affecting levels of other hormones. Such selective reduction of endogenous oestrogen provides targeted therapy for hormone-dependent breast cancer. This has led to improved clinical benefits in patients with these tumours. Anastrozole, letrozole and exemestane all have impressive antitumour effects in postmenopausal women with breast cancer and they are at least as beneficial as or better than other established endocrine agents when used to treat hormone-sensitive cancer in the advanced setting or as an adjuvant to surgery in earlier stages of the disease; ongoing trials are exploring the use of AIs in the preventative setting. Third generation inhibitors are well tolerated, having no greater side effects than might be expected from oestrogen suppression. Important differences in endocrinological and molecular effects exist between AIs and SERMs. These have implications for the preferred drug sequence and setting in which AIs are used. Since the major obstacle to more widespread use is primary/acquired resistance, discovery of the mechanisms by which resistance occurs offers hope for the future. More detailed study of AIs will yield important information about the involvement of oestrogen on the development and progression of breast cancer. Consequently AIs offer major clinical benefits to patients with breast cancer and the promise of relatively nontoxic intervention in women at high risk of the disease.
Breast Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK. wmiller@staffmail.ed.ac.uk
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D000273:Adipose Tissue / Q000201:enzymology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D001141:Aromatase / Q000502:physiology; D047072:Aromatase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects / Q000201:enzymology; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D020847:Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D009363:Neoplasm Proteins; D001141:Aromatase