Guidance on the use of trastuzumab for the treatment of advanced breast cancer

Approximately 32,000 new cases of breast cancer were reported in England and Wales in 1996. In 1998, breast cancer caused over 11,000 deaths in England and Wales and was the leading cause of death in women aged 35 to 54 years.

Advanced and metastatic breast cancer (MBC) are defined by clinical staging based on the tumour, node and metastasis staging system (stage III denotes locally advanced disease and stage IV indicates metastatic breast cancer).

Between 16% and 20% of women initially presenting with breast cancer have advanced disease with distant metastases and around 50% of those presenting with early or localised breast cancer will eventually develop MBC.

Some breast tumours contain an amplification of the human epidermal growth factor receptor (HER2), which causes overexpression of the HER2 protein and is associated with a poorer prognosis. Approximately 15% to 20% of people with MBC overexpress HER2 at level 3 or more, measured by immunohistochemical techniques. The average period of survival after diagnosis of MBC is 18 to 24 months, but this is reduced by up to 50% for patients overexpressing HER2.

First-line systemic therapy for advanced or metastatic breast cancer is chemotherapy for oestrogen receptor-negative patients (usually an anthracycline-containing regimen or sometimes a combination of cyclophosphamide, methotrexate and fluorouracil), and hormone manipulation therapy for oestrogen receptor-positive patients. However, the choice of therapy is influenced by the rate of progression and distribution of disease and by whether the drugs have already been administered as adjuvant therapies.

Current NICE guidance states that docetaxel and paclitaxel should be available for the treatment of advanced breast cancer where initial cytotoxic chemotherapy (including an anthracycline) has failed or is inappropriate.