title: An integrated view of aromatase and its inhibition.
abstract: Aromatase inhibition has become a major treatment strategy for postmenopausal women with oestrogen-dependent breast cancer. Its optimal application is, however, dependent upon (i) the accurate identification of cancers which are ultimately dependent upon the activity of the aromatase enzyme, (ii) the use of the best method/inhibitor by which to blockade aromatase activity. The single best predictor of response to aromatase inhibitors is the presence of tumour oestrogen receptors; receptor-negative cancers rarely respond whereas those with high levels seem particularly likely to benefit. However, there is a need for additional discriminatory markers. The use of microarray technology coupled with neoadjuvant therapy is likely to yield promising candidate genes. The finding that, amongst peripheral tissues, the tumour itself may have high activity has led to the suggestion that the tumour aromatase measurements may be predictive; however, in situ studies and the lack of robust assays for tumour aromatase suggest that tumour aromatase may not be an influential marker. Whilst drugs such as anastrozole, exemestane, formestane and letrozole are all effective and specific inhibitors of aromatase, they differ in structure, potency and mechanism of action. Thus, differential sensitivity of tissues/tumours and non-cross resistance mean inhibitors are not equivalent and individual agents may have differing roles according to the setting in which they will be used. Aromatase inhibitors have evolved as key endocrine agents in the treatment of breast cancer. They offer the promise of rational treatment management based on the accurate identification of individual cohorts of tumours responsive to specific drugs.
authors: Breast Unit Research Group, Western General Hospital, Edinburgh, Scotland EH4 2XU, UK. w.r.miller@ed.ac.uk
authors: W R
authors: WR
authors: Miller
authors: T J
authors: TJ
authors: Anderson
authors: D B
authors: DB
authors: Evans
authors: A
authors: A
authors: Krause
authors: G
authors: G
authors: Hampton
authors: J M
authors: JM
authors: Dixon
mesh_terms: D001141:Aromatase / Q000096:biosynthesis; D047072:Aromatase Inhibitors; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004967:Estrogens / Q000032:analysis / Q000096:biosynthesis; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D020360:Neoadjuvant Therapy; D020411:Oligonucleotide Array Sequence Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001141:Aromatase; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen