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Breast cancer remains the second leading cause of cancer death in women in the US and it is estimated that 40,460 American women will die of the disease in 2007.1 Moreover, recurrence has a significant impact on breast cancer mortality. Indeed, distant metastasis; the most common form of recurrence in the majority of cases2-4; represents the main cause of death in women with breast cancer.5 In recent decades improvements in early detection and the recognized benefits of adjuvant systemic therapy in reducing risk of distant relapse has contributed to a steady decline in breast cancer mortality,6,7 but despite these advances distant metastasis remains a challenge. Improvements in screening and imaging techniques have helped in the early detection of breast cancer and this, in turn, has resulted in a greater number of patients presenting with early-stage breast cancer.
In patients with early disease, a multimodal approach to treatment is essential for improving survival. Breast cancer recurrence, particularly distant recurrence, in women with early stage disease is associated with increased mortality.8 Treatments that can address the risk of breast cancer recurrence, especially distant metastases, have the potential to remain disease-free and improve overall survival in women with early-stage breast cancer. Adjuvant systemic therapy has demonstrated its benefits in reducing the risk of occult micrometastatic infiltration and is now recommended clinical practice for patients with nodepositive and high-risk, node-negative breast cancer.9 The challenges associated with distant recurrence in early-stage breast cancer are discussed in this review, with a focus on adjuvant endocrine therapy.
Early Breast Cancer and Distant Metastases
Widespread screening coupled with advances in imaging technologies has resulted in earlier detection of breast cancer. Consequently, more than half of the women currently presenting with breast cancer in the US have an early-stage form of the disease.10 Early-stage invasive breast cancer is defined as breast cancer that has not spread beyond the breast or the axillary lymph nodes, and includes ductal carcinoma in situ, stage I, stage IIA, stage IIB, and stage IIIA breast cancers (see Table 1).9