Estrogens Aromatase and Risk of Breast Cancer

Many of the etiological factors associated with BC have a hormonal component (1). Additionally, high BC risk has been related to increased E exposure from either endogenous (41-46) or exogenous sources (47, 48). Polymorphisms in the aromatase gene in women at high BC risk (49,50), and enhanced aromatase activity in the breasts of women with BC (51, 52) have been reported. Conversely, E deprivation may protect against the disease (53,54). For example, ovarian ablation before the age of 35 years is calculated to reduce subsequent BCs by two thirds (53).

These observations provide the rationale for the use of endocrine therapy as preventative measures against BC in women with high risk ofthe disease. Four trials using tamoxifen have been published (55-57), as has a fifth trial using raloxifene (58). Although there are differences among studies, a recent metaanalysis of the tamoxifen trials indicated that results were compatible with a 42% reduction in short term incidence of breast cancer with tamoxifen use (59).

These studies provide the impetus to use aromatase inhibitors as preventative agents and determine whether they may be more effective than selective ER modulators (SERMs).

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