First-line endocrine treatment of breast cancer: aromatase inhibitor or antioestrogen?

Until recently, endocrine therapy for breast cancer was relatively simple. If the tumour expressed hormone receptors, regardless of stage and age, tamoxifen was indicated. While this largely remains the case for premenopausal women, clinical trials in postmenopausal women have broadened our choice to include one of three selective aromatase inhibitors (AIs), the nonsteroidal agents anastrozole or letrozole and the steroidal agent exemestane. Comparative data concerning the efficacy, toxicity, tolerability and cost of AI vs tamoxifen continues to evolve with over 40 000 women slated to be involved in clinical trials. Currently, tamoxifen remains an appropriate choice for adjuvant treatment, and will remain so unless a clear survival advantage emerges for adjuvant AI therapy. However, anastrozole is widely seen as a useful alternative, with particular merit for patients prone to the development of serious tamoxifen side effects. For endocrine therapy naïve advanced disease, several trials have provided evidence that a nonsteroidal AI has replaced tamoxifen as optimal treatment. In the neoadjuvant setting, letrozole was also more effective than tamoxifen, both in terms of response rates and the incidence of breast-conserving surgery, and so AI therefore also dominates this evolving indication. The ongoing adjuvant clinical trials ask all the relevant questions regarding tamoxifen and AI in combination, sequence and duration, except for 5 years of an AI vs a longer period. For both the advanced and early-stage disease, resistance remains the key obstacle to overcome, and trials that combine endocrine agents with signal transduction inhibitors such as HER1 and HER2 kinase inhibitors, farnesyl transferase inhibitors, mTOR inhibitors as well as COX2 inhibitors are being developed in a concerted attempt to address this problem.