Research on a new anti-breast cancer drug therapy, a possiblealternative to Tamoxifen, shows successful results. Dr Muiris Houston, Medical Correspondent, reports
Womwn in the Republic have a one in 13 chance of developing breast cancer in their lifetime. According the National Cancer Registry report, Cancer in Ireland 1994-1998, 631 women die from the disease every year. But the overall survival rate from the disease five years after diagnosis is 78 per cent, rising to 97 per cent for those diagnosed with early breast cancer.
Much of this survival can be attributed to a four-pronged approach to treatment, involving surgery, radiotherapy, chemotherapy and hormone therapy. Almost one in four women in the State will be treated with a combination of surgery and hormone therapy.
Hormone therapy is based on the finding that many breast cancers are oestrogen sensitive. In other words, they grow more rapidly by feeding off the oestrogen in women's bodies. Blocking this effect helps to prevent recurrence and improve survival in women whose cancer has spread beyond the breast at the time of diagnosis.
For more than 20 years, the drug tamoxifen has been the standard hormone therapy used by doctors. It works by blocking the receptors on cells, which normally recognise oestrogen and allow it to enter the cell.
As a result, tamoxifen slows the growth of the tumour and can even shrink it. It is also used to prevent the recurrence of a breast cancer that has been surgically removed.
Tamoxifen is widely used and its efficacy is well proven. It reduces recurrence rates by about 50 per cent when used as a hormone therapy by patients with oestrogen receptor positive tumours. Taken for up to five years after diagnosis, it reduces the chance of recurrence and death in post-menopausal women.
In women whose breast cancer has spread to bone, liver or lung (metastatic spread), tamoxifen prolongs remission in about 50 per cent of cases. The hormone treatment is particularly effective in post-menopausal patients with oestrogen receptor positive disease which has spread
Tamoxifen has also been shown to reduce the risk of breast cancer in healthy women who are at an increased risk of developing the disease.
However, some women have developed metastases (secondary spread) while on tamoxifen and so are considered resistant to it. This led to the use of a new class of drug - the selective aromatase inhibitors - in patients who had experienced tamoxifen failure.
The new agents work by blocking the conversion of oestrogen precursor into oestrogen itself. As a result, there is less oestrogen circulating in the body to promote the further growth of breast cancer cells.
Selective aromatase inhibitors (SAI) had been shown to improve survival in post-menopausal women with secondary spread who had relapsed during or after treatment with tamoxifen. Now, with the publication of a major trial in the Lancet, comes scientific evidence that the drug anastrozole is an effective option in the treatment of post-menopausal women with early breast cancer.
The ATAC trial compared the safety and efficacy of tamoxifen with the SAI anastrazole alone and in combination. With over 9,000 patients, it is the largest hormone therapy trial in breast cancer yet completed.
Led by Prof Michael Baum from University College London, the international researchers included consultant surgeons from Dublin and Galway.
While originally designed to last five years, the results at 33 months follow up were such as to encourage a "fast-track" publication by the Lancet. They showed anastrozole to be significantly better than tamoxifen, with a relative risk reduction for tumour recurrence of 22 per cent. In addition, the new drug showed a slight improvement in three-year survival. Combining both drugs gave no additional benefit.
There was also good news in terms of side-effects. Although tamoxifen is a "clean" drug with a low incidence of cancer of the body of the uterus and clotting problems, anastrazole had an even lower risk of side-effects. However, the new drug was associated with more bone fractures than treatment with tamoxifen.
So, is this the end of the line for tamoxifen? Not quite. The American Society of Clinical Oncologists have not yet embraced anastrazole as the new standard for hormone therapy in breast cancer.
This is principally because patients with breast cancer have a long period when recurrence is a possibility. In addition, we know that tamoxifen has a significant "carry-over effect" ; that is, it continues to protect for some time after the patient ceases treatment. We therefore need a full five-year follow-up of anastrozole in order to give a final verdict on whether it will become the standard treatment.
Where does this leave the patient? If you are currently taking tamoxifen, the new data does not support a switch to anastrazole. The findings for anastrazole are applicable only to newly diagnosed patients with early breast cancer who have had initial treatment with surgery, chemotherapy or radiotherapy.
For such a woman, who is post-menopausal and whose tumour is sensitive to oestrogen, there is now a choice of hormone therapy between anastrazole and tamoxifen.
To see whether the 20-year reign of tamoxifen has finally ended, we will have to await the results of further clinical trials.