John Mann, Queen’s University Belfast, takes a look at drugs on the market.

In this issue: The best drug for breast cancer?

There have been several well-publicised cases recently where breast cancer patients have been given the new drug herceptin from their hard-up NHS Trust hospitals. The drug is certainly expensive but does it offer advantages over the other tried and tested treatments for breast cancer? 

For over 20 years the main treatment of breast cancer has been tamoxifen (1) (Novaldex). This drug acts by binding to oestrogen receptors in the cytoplasm of tumour cells, thus denying those receptors access to oestrogens, eg  oestrone (2), the latter being required for the growth and reproduction of ca  35 per cent of mammary tumour cell types. Normally, the oestrogen–receptor complex passes from the cytoplasm into the nucleus of the cell where it binds to DNA at a ‘hormone response element’, which triggers a burst of replication and eventual production of new protein. 

More recently, new drugs – aromatase inhibitors – have begun to compete with tamoxifen for the treatment of breast cancer. These drugs act by inhibiting one of the enzymes (aromatase) required for the production (biosynthesis) of oestrogens, so once again the cancer cells are starved of the oestrogens necessary for growth. A recently completed, large-scale clinical trial suggested that aromatase inhibitors, such as anastrozole (3) (Arimidex) and letrozole (4) (Femara), can be even more effective than anti-oestrogens like tamoxifen, but again these drugs require the tumour cells to be oestrogen-dependent for good clinical benefit. 

Herceptin (or Trastuzumab) works in a different way. The drug is a monoclonal antibody that has a specific affinity for the protein HER2, which is produced in abnormally large amounts (over-expressed by 10- to 100- fold) in ca  20 per cent of mammary tumours. The protein is a human epidermal growth factor receptor and is embedded in the cell membrane of the tumour cells, causing them to be permanently switched on for growth. The antibody herceptin binds to HER2 and inhibits this growth-promoting activity. The drug is only effective in those mammary tumours that over-express HER2 and is expensive, costing the NHS ca  £22K per patient per year. That said, these HER2 tumours are aggressive, and there is growing evidence that the use of chemotherapy in conjunction with herceptin can lead to longer periods of disease-free remission for patients suffering from breast cancer, and that has to be rated as money well spent. The most recent results suggest that recurrence rates for tumours can be reduced by as much as 45 per cent. 

Given the growing evidence of the efficacy of anastrozole and letrozole coupled with the new results using herceptin, the pressures on the NHS to allow use of these new drugs can only increase.