Treatment strategies that effectively reduce early recurrence risk in postmenopausal women with endocrine-sensitive breast cancer: AIs upfront vs. switching

Abstract

Several large, well-controlled clinical trials have now established that the aromatase inhibitors (AIs), including letrozole, anastrozole, and exemestane, are more effective than tamoxifen when used as adjuvant endocrine therapy in postmenopausal women with breast cancer. Yet, it is an open question as to how these drugs should be best integrated into the adjuvant treatment regimen. Both letrozole and anastrozole have shown efficacy over tamoxifen when used as initial adjuvant therapy (initiated just following surgery for breast cancer), while exemestane and anastrozole have been used as switching adjuvant therapy, i.e., following 2-3 years of initial adjuvant tamoxifen therapy, with proven efficacy over continued tamoxifen. Studies demonstrate that recurrence risk peaks in the early period after surgery, and that distant metastases in particular, accounting for most of the early recurrences, have worse survival rates when compared with other types of recurrences. Treatments that reduce recurrences, especially distant metastases, in this early period are therefore likely to improve overall survival (OS) and reduce mortality from breast cancer. In this review, we discuss early recurrence risk among postmenopausal women with successfully treated early breast cancer, the efficacy of the different AIs in reducing early recurrences and distant metastases when incorporated into adjuvant therapy, and the evidence for increased OS when AIs are used as initial or switch adjuvant therapy.

Fig. 1

5-Year disease-specific survival of breast cancer patients having local recurrence (LR), recurrence at regional lymph nodes (RNR), or distant recurrence (DR). Disease-specific survival for LR was significantly different from RNR or DR patients (P < 0.0001) (Data from Elder et al. 2006)

Fig. 2

Hazard ratio for death in patients with no recurrence (No R), contralateral recurrence (CR), locoregional recurrence (LRR), or distant recurrence (DR). The associated P-value for comparison with No R group is shown (Data from Lamerato et al. 2005)