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Effect of aromatase inhibitors on the lipid profile of postmenopausal breast cancer patients
The two most commonly used alternative strategies of endocrine treatment in postmenopausal women with hormone-receptor-positive breast cancers are either the interference with estrogen signaling by a selective estrogen-receptormodulator, such as tamoxifen, or the inhibition of endogenous estrogen production via an aromatase inhibitor (AI). Tamoxifen has been used effectively for over 30 years and it is generally accepted that it exerts a beneficial effect on lipid profiles. Still, its use has been questioned especially in recent years, following indication of an increased risk of endometrial cancer, thromboembolic eventsand tolerability concerns, along with, most importantly, the development of resistance during long-term adjuvant treatment. On the other hand, inhibition of aromatase, the enzyme that converts androgens to estrogens, with an AI has been shown to be an effective alternative to tamoxifen in multiple clinical trials with anastrozole, letrozole and exemestane. At the same time, due to the high levelsof estrogen deprivation caused by AIs, there is uncertainty over the long-term safety of these agents, in particular with respect to the effects on bone metabolism of postmenopausal women and the lipid profile, and thus, cardiovascular disease. Current data on AIs showing favorable, neutral or unfavorable effect on different lipid parameters in various studies, do not allow the drawing of anyfinal conclusions about their effect on lipid metabolism. However, considering disease outcome, particularly in high-risk patients, the benefits of receiving an AI are likely to outweigh the disadvantages of any changes to lipid profiles. Therefore, each patient should be carefully evaluated before the appropriate therapy is decided and blood lipid levels should be monitored during adjuvant hormonaltreatment; the instigation of lipid-lowering treatment should be undertaken if required.
KEYWORDS: anastrozole n aromatase inhibitor n breast cancer n endocrine therapy
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exemestane n letrozole n postmenopausal lipid n tamoxifen

Adjuvant hormonal therapy is the treatment of choice in postmenopausal women with endocrine responsive breast cancer, which aims to reduce the risk of recurrenceand, therefore, increase overall survival. The two most commonly used endocrine therapies are the interference with estrogen signaling by binding to the estrogen-receptor protein with a selective estrogen-receptor modulator (SERM), such as tamoxifen, or the inhibition of endogenous estrogen production via using an aromatase inhibitor (AI). Tamoxifen has been the standard adjuvant endocrine therapyfor postmenopausal women with breast cancer for the last 30 years; the main benefit is prolongation of disease-free and overall survival of the patient [1] . In addition, tamoxifen treatment has a positive effect on lipid metabolism that seems to result in a reduced risk of cardiovascular disease [2–5] . Tamoxifen decreases the activity of two lipolytic enzymes
10.2217/CLP.10.4 © 2010 FutureMedicine Ltd

and induces hyperlipidemia [3] . Tamoxifen also affects the plasma lipoprotein–lipid concentration and lipid transfer protein I activity in postmenopausal women [5] . In breast cancer patients, tamoxifen decreases levels of lipoprotein (a) (Lp[a]) and IGF-I [4] . Using all these mechanisms tamoxifen reacts beneficially to women’s lipid profiles. However, use of tamoxifen has beenquestioned in recent years, owing to increased risk of endometrial cancer, thromboembolic events and tolerability concerns. These risks are considered to be a consequence of tamoxifen’s partial estrogen-agonistic effect. Furthermore, development of resistance to tamoxifen limits the duration of effective treatment to 5 years [6] . More recently, the third-generation aromatase inhibitors anastrozole,...