Fulvestrant – a new treatment for postmenopausal women with hormone-sensitive advanced breast cancer

Approximately 75% of breast tumours in postmenopausal women are positive for the oestrogen receptor (ER) and/or the progesterone receptor (PgR) and are, therefore, potential candidates for endocrine treatment. Fulvestrant is a new type of ER antagonist with no agonist effects and a novel mode of action; it binds, blocks and degrades the ER, leading to a reduction in cellular ER and, consequently, in PgR levels. This novel mode of action results in a lack of cross-resistance with other commonly used endocrine treatments. In Phase III trials in postmenopausal women with advanced breast cancer progressing on prior anti-oestrogen therapy, fulvestrant was at least as effective as the third-generation aromatase inhibitor, anastrozole, in terms of time to progression and objective response, and was associated with similar overall survival. In the first-line setting, fulvestrant showed similar efficacy to tamoxifen in patients with ER-positive and/or PgR-positive disease. Efficacy in more heavily pretreated patients has also been demonstrated in the fulvestrant compassionate use programme. Fulvestrant is well tolerated, being associated with a significantly lower incidence of joint disorders compared with anastrozole, and a lower incidence of hot flushes compared with tamoxifen. Fulvestrant, therefore, provides clinicians with a useful additional treatment for hormone-sensitive advanced breast cancer in postmenopausal women. Ongoing trials will help to clarify the optimal position of fulvestrant in the endocrine treatment sequence for these patients.