Preoperative hormonal therapy: results and implications

The development of presurgical endocrine strategies for the treatment of primary breast cancer was developed initially from the application of such treatments in elderly patients to try to avoid the potential complications of surgery. Although there are few data available, one study has indicated that in oestrogen receptor (ER)-positive tumours clinical responses are as frequent with endocrine therapy as with cytotoxic chemotherapy. The optimal duration of treatment is not established, although most trials range between 3 and 4 months. A randomized trial indicated that the aromatase inhibitor letrozole was significantly better than tamoxifen when given as neoadjuvant therapy to patients ineligible for breast conserving surgery (BCS). A similar result was obtained for anastrozole in another randomized trial (IMPACT) but no greater efficacy than tamoxifen was seen in tumours in which BCS was possible. These two studies have provided an indication that aromatase inhibitors may be significantly more effective than tamoxifen in HER2-positive tumours. In the IMPACT trial the changes in the proliferation marker Ki67 were predictive of outcome in the large ATAC adjuvant trial, supporting the concept of using the neoadjuvant scenario to assess new therapeutic agents/ideas prior to initiating large phase 3 studies. The relatively easy availability of tissue samples during before and during neoadjuvant trials makes this a particularly valuable arena for translational research studies with new targeted agents in combination with hormonal treatment.