Application of aromatase inhibitors in endocrine responsive breast cancers.

Aromatase (estrogen synthetase) inhibitors (AIs) have been incorporated into adjuvant treatment of early-stage breast cancer in post-menopausal women and their role in pre-menopausal is being investigated. Several questions regarding AIs remain unanswered: optimal sequence with tamoxifen; optimal duration and the best agent in the class. The benefits of extending therapy beyond 5 years has been established by the MA17 trial and many follow-on trials are exploring prolonged therapy. Several strategies to overcome de novo and acquired resistance are being explored. Improving on the "total estrogen blockade" by adding fulvestrant is one example; blocking collaborating cell signaling pathways is another. Candidate targets for this include the erbB2, IGF1R and the mTOR cell survival pathway. Identification of both host (pharmacogenomic) and tumor (genomic) signatures as prognostic and predictive factors will help to select patients for appropriate therapies in the future and reduce the number needed to treat to benefit a few.