Breast tumour resistance overcome

Scientists have discovered why some breast cancers fail to respond to the drug tamoxifen – and found a way to combat the problem.

They have shown that another cancer drug – gefitinib – may be able to destroy a tumour’s resistance to tamoxifen’s anti-cancer effect. If confirmed, the finding could provide new hope for many patients. The study, by Baylor College of Medicine, is published in the Journal of the National Cancer Institute. Tamoxifen has been shown to reduce the risk of death from women with advanced breast cancer by about 15% over 10 to 15 years. However, the drug only works for women whose tumours are sensitive to the female sex hormone oestrogen. These are known as ER-positive tumours. And even among this group, it appears that only 40% to 50% actually benefit from taking tamoxifen. Studies have shown that resistance to the drug is higher among ER-positive tumours that also produce high levels of two other chemicals, called HER2 and AIB1.The Baylor team studied molecular interactions in breast cancer cells that expressed high levels of both HER2 and AIB1. They found that, in these cells, tamoxifen actually seemed to promote the effect of oestrogen, and stimulate tumour growth. However, when the breast cancer cells were treated with gefitinib this seemed to restore the ability of tamoxifen to block both the action of oestrogen and tumour growth. The researchers say that using drugs like gefitinib alone has little impact on tamoxifen-resistant ER-positive tumours. But they say their work does provide a strong case for combining the two drugs to overcome resistance. ‘More research needed’ Dr Michelle Barclay of the charity Breakthrough Breast Cancer, said: “These are interesting results that could, in the long term, benefit some women who unfortunately develop a resistance to tamoxifen. “However, the results are very preliminary and we look forward to further research into this combination, and results of clinical trials. “Studies like these are important as they enable us to understand more about the biology of breast cancer and how different treatments work, ultimately aiming to provide the best treatment suitable for each woman.” Samia al Qadhi, of Breast Cancer Care, was also very positive about the research. She said: “We know that many women worry about the possible implications of being told that their breast cancer is resistant to tamoxifen. “We look forward to seeing the results of clinical trials being carried out into the efficacy of gefitinib in restoring tamoxifen’s anti-cancer properties in these women.” (Source: BBC News: June 2004)