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.