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Role of aromatase inhibitors in breast cancer.

Carpenter R, Miller WR - Br. J. Cancer (2005)

Bottom Line: In addition, with increased efficacy and favourable safety and tolerability profiles, the aromatase inhibitors are starting to challenge tamoxifen as first choice endocrine treatment in a number of settings.Potential differences in side-effect profiles may appear between the steroidal and nonsteroidal aromatase inhibitors when used in long-term settings.Thus, it has been suggested that the steroidal agents have favourable end organ effects; for example, the steroidal inhibitor, exemestane, has minimal negative effects on bone and lipid metabolism in animal and clinical studies.

View Article: PubMed Central - PubMed

Affiliation: The Breast & Endocrine Unit, St Bartholomew's Hospital, London EC1A 7BE, UK.

ABSTRACT
Primarily, the role of the aromatase inhibitors has been investigated in postmenopausal women with breast cancer, although it is also now being assessed in premenopausal patients following ovarian ablation/suppression. Aromatase inhibitors markedly suppress endogenous oestrogens without directly interacting with oestrogen receptors, and thus have a different mechanism of action to the antioestrogen, tamoxifen. The inhibitors may be divided into subgroups according to their structure (steroidal and nonsteroidal), and there appears to be a lack of cross-resistance between the classes of aromatase inhibitors enabling them to be used sequentially and potentially to prolong endocrine hormone therapy. In addition, with increased efficacy and favourable safety and tolerability profiles, the aromatase inhibitors are starting to challenge tamoxifen as first choice endocrine treatment in a number of settings. Potential differences in side-effect profiles may appear between the steroidal and nonsteroidal aromatase inhibitors when used in long-term settings. Thus, it has been suggested that the steroidal agents have favourable end organ effects; for example, the steroidal inhibitor, exemestane, has minimal negative effects on bone and lipid metabolism in animal and clinical studies. This paper provides an overview of the current and future roles of aromatase inhibitors for breast cancer treatment.

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Mechanisms of action of tamoxifen and exemestane.
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fig1: Mechanisms of action of tamoxifen and exemestane.

Mentions: Unlike tamoxifen, aromatase inhibitors do not directly interact with the oestrogen receptor but indirectly affect signalling in postmenopausal women by blocking the conversion of adrenal androgens to oestrogen in peripheral (ie non-ovarian) tissues, including the breast itself (Figure 1; Miller, 1991). Enhanced aromatase activity has been observed in adipose tissue adjacent to breast cancers (O'Neill et al, 1988), and may promote growth of malignant cells (O'Neill et al, 1988). Aromatase inhibitors inhibit in situ oestrogen synthesis in both tumour and non-malignant breast tissue (Miller and Dixon, 2001), and have demonstrated efficacy in suppressing peripheral oestrogen synthesis in postmenopausal women (Smith and Dowsett, 2003).


Role of aromatase inhibitors in breast cancer.

Carpenter R, Miller WR - Br. J. Cancer (2005)

Mechanisms of action of tamoxifen and exemestane.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361691&req=5

fig1: Mechanisms of action of tamoxifen and exemestane.
Mentions: Unlike tamoxifen, aromatase inhibitors do not directly interact with the oestrogen receptor but indirectly affect signalling in postmenopausal women by blocking the conversion of adrenal androgens to oestrogen in peripheral (ie non-ovarian) tissues, including the breast itself (Figure 1; Miller, 1991). Enhanced aromatase activity has been observed in adipose tissue adjacent to breast cancers (O'Neill et al, 1988), and may promote growth of malignant cells (O'Neill et al, 1988). Aromatase inhibitors inhibit in situ oestrogen synthesis in both tumour and non-malignant breast tissue (Miller and Dixon, 2001), and have demonstrated efficacy in suppressing peripheral oestrogen synthesis in postmenopausal women (Smith and Dowsett, 2003).

Bottom Line: In addition, with increased efficacy and favourable safety and tolerability profiles, the aromatase inhibitors are starting to challenge tamoxifen as first choice endocrine treatment in a number of settings.Potential differences in side-effect profiles may appear between the steroidal and nonsteroidal aromatase inhibitors when used in long-term settings.Thus, it has been suggested that the steroidal agents have favourable end organ effects; for example, the steroidal inhibitor, exemestane, has minimal negative effects on bone and lipid metabolism in animal and clinical studies.

View Article: PubMed Central - PubMed

Affiliation: The Breast & Endocrine Unit, St Bartholomew's Hospital, London EC1A 7BE, UK.

ABSTRACT
Primarily, the role of the aromatase inhibitors has been investigated in postmenopausal women with breast cancer, although it is also now being assessed in premenopausal patients following ovarian ablation/suppression. Aromatase inhibitors markedly suppress endogenous oestrogens without directly interacting with oestrogen receptors, and thus have a different mechanism of action to the antioestrogen, tamoxifen. The inhibitors may be divided into subgroups according to their structure (steroidal and nonsteroidal), and there appears to be a lack of cross-resistance between the classes of aromatase inhibitors enabling them to be used sequentially and potentially to prolong endocrine hormone therapy. In addition, with increased efficacy and favourable safety and tolerability profiles, the aromatase inhibitors are starting to challenge tamoxifen as first choice endocrine treatment in a number of settings. Potential differences in side-effect profiles may appear between the steroidal and nonsteroidal aromatase inhibitors when used in long-term settings. Thus, it has been suggested that the steroidal agents have favourable end organ effects; for example, the steroidal inhibitor, exemestane, has minimal negative effects on bone and lipid metabolism in animal and clinical studies. This paper provides an overview of the current and future roles of aromatase inhibitors for breast cancer treatment.

Show MeSH
Related in: MedlinePlus