Safely promoting breast-conserving surgery and preventing early relapses with an aromatase inhibitor

Neoadjuvant therapy improves patient outcomes substantially by increasing the rate of breast-conserving surgery. Following primary surgery, women with hormone-sensitive early breast cancer remain at risk for loco-regional and systemic recurrence. The most common relapse event, distant metastases, is associated with the poorest outcomes. As a neoadjuvant therapy, anastrozole, letrozole, and exemestane have been investigated in phase 3 studies and have shown efficacy in this setting. All three aromatase inhibitors (AIs) significantly improved the rate of breast-conserving surgery. As initial adjuvant therapy, the third-generation AIs anastrozole and letrozole more effectively reduce recurrence risk compared with tamoxifen following surgery, especially in the first 2 years, when the risk is greatest. Tamoxifen, once the standard initial therapy, is associated with improved disease-free survival but may be more effective at reducing loco-regional recurrence than distant metastases. Initial adjuvant letrozole therapy has also shown a pronounced reduction in the risk of distant metastases early on in the course of therapy. If AIs are not used upfront, sequential use of exemestane or anastrozole following tamoxifen provides greater protection against relapse than continuing on tamoxifen. Side effects associated with estrogen deprivation of AIs are less serious than those of tamoxifen and are easily managed. Various molecular markers are under study as surrogates to predict response to neoadjuvant therapy, which may in turn predict responsiveness to adjuvant therapy. Surgeons treating breast cancer patients and prescribing endocrine therapy should be aware of all treatment strategies, including neoadjuvant and adjuvant hormonal therapy, and inform their patients of the benefits and the potential side effects. Early and long-term-risk reduction with AI treatment should be discussed with patients, as should the management of common AI-associated adverse events.