Role of endocrine therapy in the neoadjuvant surgical setting

Most neoadjuvant (preoperative) therapy of breast cancer has involved the use of chemotherapy, but primary endocrine therapy has also been shown to be effective in postmenopausal women with estrogen receptor-positive tumors. Neoadjuvant therapy can reduce tumor volume, permitting surgery for otherwise inoperable tumors or allowing breast-conserving surgery rather than mastectomy for operable tumors. The preoperative treatment setting also allows for assessment and comparison of responses to different agents, which may then be used in the adjuvant therapy setting following surgery. Since tumor biopsies can be obtained before, during, and after preoperative therapy, the relationship between biomarkers and response or resistance to surgery can be investigated. In the Edinburgh Breast Unit, neoadjuvant endocrine therapy with aromatase inhibitors has been more successful than with tamoxifen. Recurrence rates following preoperative endocrine therapy and breast-conserving surgery have been acceptably low, provided that radiation therapy was also administered postoperatively. Both the probability of response to neoadjuvant letrozole or tamoxifen and the degree of tumor shrinkage increased as estrogen receptor expression increased, consistent with the results of other studies. Attempts to identify biomarkers of response to neoadjuvant endocrine therapy are under way, with early indications that reduced cell proliferation 14 days after initiation of treatment correlates with responses to tamoxifen.