Estrogen plays an important role in the skeletal health of all women. Many therapies used in the treatment of breast cancer reduce estrogen levels and have the potential to affect bone negatively by increasing the risk of osteoporosis and associated bone fractures. The long-term effects of systemic endocrine therapy on bone, therefore, are an important consideration in the adjuvant setting. Tamoxifen has been shown to have a moderate protective effect on postmenopausal bone due to its partial estrogen agonist activity; however, its long-term use is potentially associated with negative side effects, such as an increased risk of thromboembolic disease and endometrial cancer. Newer agents, the third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, for example, do not possess estrogen agonist effects and have improved breast cancer outcomes when compared to the standard 5 years of tamoxifen. However, patients treated with adjuvant AIs have been shown to have an increased incidence of osteoporosis and osteoporotic fractures. In order to select the optimal adjuvant therapy for each patient, it is important to assess the overall risk:benefit ratio for each endocrine strategy. All postmenopausal women should follow published guidelines to assess the risk of osteoporosis and, where appropriate, they should receive bone mineral density monitoring. Postmenopausal women with breast cancer who are at increased risk of osteoporotic fracture should be identified and managed with appropriate nonpharmacologic and pharmacologic measures. © 2005 Wiley-Liss, Inc.
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