Use of aromatase inhibitors in the adjuvant treatment of breast cancer.

Abstract

The value of endocrine treatment of early breast cancer has been illustrated by the antioestrogen, tamoxifen, which has now been available for nearly 30 years. However, if the recognised side effects and pharmacological properties of tamoxifen are taken into consideration, it is possible that other endocrine treatments that are now available can provide equal or superior efficacy, along with improved tolerability. One such group of agents is the aromatase inhibitors specifically the new-generation triazole aromatase inhibitors, such as anastrozole and letrozole, which have both shown tolerability and efficacy advantages over standard treatments in postmenopausal women with advanced breast cancer. There are convincing reasons why the new generation of aromatase inhibitors have advantages over tamoxifen. For instance, from their agonist properties, the effects on the endometrium and tumour stimulation seen with tamoxifen would not be expected, nor would the visual disturbances that have been associated with the triphenylethylene compounds, including tamoxifen. A number of aromatase inhibitors, for instance, anastrozole, letrozole and exemestane, are currently being investigated for treatment of early breast cancer. The results of the trials of aromatase inhibitors and tamoxifen will, in the next few years, define whether or not the new-generation aromatase inhibi- Endocrine-Related Cancer (1999) 6 231-234 tors have a role to play in the treatment of postmenopausal women with early breast cancer.

The molecular, cellular and clinical consequences of targeting the estrogen receptor following estrogen deprivation therapy

“…Aromatase inhibitors target a cytochrome P450 type enzyme called aromatase (CYP19A1) that converts androgen to estrogen, thus blocking the biosynthesis of estrogen that fuels the proliferation of ER-positive breast cancer. Newer AIs made it possible to achieve a safer therapeutic benefit for postmenopausal breast cancer patients (Santen et al , 2009) and as new molecules became more specific and less toxic it has become possible to initiate larger and longer clinical studies to compare the therapeutic effects with tamoxifen, in the adjuvant setting (Baum, 1999). …”

Effects of Femara and Tamoxifen on Proliferation of FM3A Cells in Culture

“…These agents are only effective in patients in whom ovarian function has been effectively suppressed either naturally or therapeutically (Buzdar, 2003). One such group of agents is the aromatase inhibitors specifically the new generation triazole aromatase inhibitors, such as anastrozole and letrozole, which have both shown tolerability and efficacy advantages over standard treatments in postmenopausal women with advanced breast cancer (Baum, 1999). Third-generation aromatase inhibitors have become the gold standard in second-line therapy and are being considered as an alternative to tamoxifen for first-line endocrine therapy based on results from randomized trials in postmenopausal patients with metastatic, receptorpositive, or receptor-unknown breast cancer (Mouridsen et al, 2003) In the present study, to evaluate and compare the antiproliferative effects of Tamoxifen and Femara, estrogen receptor positive breast cancer cell line FM3A was used and for this purpose labelling index, mitotic index and apoptotic index were evaluated as cell kinetic parameters.…”

Potent CYP19 (Aromatase) 1-[(Benzofuran-2-yl)(phenylmethyl)pyridine, -imidazole, and -triazole Inhibitors: Synthesis and Biological Evaluation

“…7 The "ATAC" (Arimidex, Tamoxifen, Alone or in Combination) trial suggested that aromatase inhibitors, specifically arimidex, may well be superior to tamoxifen (the current first-line therapy of choice) for the treatment of hormone-dependent breast cancer. 8,9 Studies have also indicated the use of aromatase inhibitors for preventive therapeutics, owing to their ability to reduce estrogen levels; a high level of plasma estrogen has been shown to be a high risk factor for subsequent breast cancer. 10 1-[(Benzofuran-2-yl)phenylmethyl]imidazoles 11 and -triazoles 12 are potent P450 AROM inhibitors, with the pyridine derivatives displaying moderate activity (Figure 1).…”

“…In vitro studies showed that letrozole significantly suppressed the endogenous aromatase-induced proliferation of MCF-7 cells . The “ATAC” (Arimidex, Tamoxifen, Alone or in Combination) trial suggested that aromatase inhibitors, specifically arimidex, may well be superior to tamoxifen (the current first-line therapy of choice) for the treatment of hormone-dependent breast cancer. , Studies have also indicated the use of aromatase inhibitors for preventive therapeutics, owing to their ability to reduce estrogen levels; a high level of plasma estrogen has been shown to be a high risk factor for subsequent breast cancer 1 Potent nonsteroidal CYP19 inhibitors. …”