Letrozole in the treatment of breast cancer

Endocrine therapy, predominantly using the antioestrogen tamoxifen, has long been a key treatment strategy for oestrogen receptor-positive breast cancer. An alternative approach is to treat patients with aromatase inhibitors, which suppress oestrogen biosynthesis. Letrozole, and other third-generation aromatase inhibitors, are highly specific and potent inhibitors of oestrogen production, which markedly reduce circulating oestrogen levels and whole-body aromatisation of androgen precursors after menopause. In postmenopausal women with hormone receptor-positive or receptor-unknown breast cancer, letrozole has been shown to be superior to megestrol acetate and aminoglutethimide in second-line treatment for advanced breast cancer. Letrozole was also superior to tamoxifen in first-line treatment for advanced breast cancer, as well as in systemic preoperative (neoadjuvant) treatment of locally advanced breast cancer. A recent adjuvant trial demonstrated significant superiority of letrozole over tamoxifen in disease-free survival, and another trial demonstrated that treatment for early breast cancer with letrozole, following 5 years of adjuvant tamoxifen (extended adjuvant therapy), significantly improved disease-free survival compared with placebo, irrespective of nodal status. Ongoing trials will determine whether the optimal use of letrozole in the adjuvant therapy of early breast cancer is as a replacement for tamoxifen, or sequenced additionally before or after tamoxifen.