New generation aromatase inhibitors in breast cancer. Weighing out potential costs and benefits

Abstract

Endocrine therapy is the oldest and still one of the most effective forms of systemic therapy for breast cancer. Unfortunately, only one-third of all breast carcinomas respond to a strategy that modifies the activity of estrogen at the level of the tumour. Therefore, it is important that patients with cancer likely to respond are reliably identified. Substantial evidence indicates that tumour estrogen receptor level is the best predictor of response to hormonal therapy. Although antiestrogen therapy is still considered the endocrine modality of choice for all stages of breast cancer, there is renewed interest in finding new agents with improved therapeutic indices. The development of agents which selectively suppress aromatase, a key enzyme in estrogen biosynthesis, can be attributed not only to the importance of extraglandular aromatase activity, but also to the unparalleled success of tamoxifen. The present status, emerging roles and concerns of the new aromatase inhibitors are discussed in order to assess their potential costs and therapeutic merit.