This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. High breast density is known to be one of the strongest risk factors for breast cancer development. Anti-estrogen agents such as tamoxifen are known to decrease breast density and decrease breast cancer development in high risk patients. Third generation aromatase inhibitors decrease circulating and breast estrogen levels. Whether these agents decrease breast density is unknown. However, recent studies in breast cancer patients have shown a decrease in the development of contralateral breast cancer in these women therefore suggesting that these agents may be a viable alternative for breast cancer prevention. Aromatase inhibitors result in estrogen depletion not only at the breast but also in other estrogen responsive systems. We will therefore explore the ability of letrozole to decrease breast density in women with high mammographic breast density. The effects of letrozole on bone turnover markers, bone density and the GH-IGF-I axis will be assesed in this pilot study. Recent preliminary data suggest that aromatase inhibitors may lead to bone density loss and increased fracture risk after 2.5 years of use. Whether approved bisphosphonates such as zoledronic acid can prevent the bone deterioration is unknown. A subset of women in this study who are receiving letrozole will also receive zoledronic acid.
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