A new generation of drugs is giving women with breast cancer greater hope of survival than in the past. Doctors are looking to the genetics revolution to decide which patients should receive a particular combination of therapies. Recent headlines have trumpeted promising results for drugs such as Arimidex, which are likely to be added shortly to the armoury of therapies available to Britain's oncologists.
Yet the transformation of breast cancer treatment really began 17 years ago, when tamoxifen started to become commonly used in Britain. The drug, which is now routinely given to women for a period of five years after breast cancer surgery, works by blocking the female hormone oestrogen, which promotes the growth of tumours. It now also appears to protect healthy women with a strong family history of the disease.
Over the last decade, there has been a 20 per cent reduction in the mortality rate in the UK - a remarkable achievement for any disease. Tamoxifen, the nationwide screening programme, far greater awareness of the disease among women and the reorganisation of hospital cancer services have all played their part. With around 39,000 women a year diagnosed with breast cancer, survival rates vary enormously according to the stage of their cancer at the time of diagnosis. Those at the earliest stage, when the tumour is less than 2cm in diameter, have a 92 per cent chance of survival after five years, but that falls to just 27 per cent for those at an advanced stage.
Genetic testing now holds the prospect of prolonging life for many women, even if ultimately they cannot be cured. Much of the emphasis is on laboratory work to identify the 80 or 90 genetic factors that encourage the cancer cells to proliferate and spread through the body, so that therapies can be tailor-made to target specific dangerous enzymes.
Professor Trevor Powles, head of the breast cancer unit at the Royal Marsden Hospital in London, believes that chemotherapies are largely responsible for the dramatic fall in mortality rates over the past decade. 'Women should be more positive about breast cancer than ever. Here, 82 per cent of the patients are clear of the disease after five years,' he says.
'The future is looking very hopeful for breast cancer. There are new treatments on the drawing board that look very promising - not pie in the sky at all.'
The latest - Arimidex - is still undergoing trials, but promises to be even more successful than tamoxifen and may ultimately replace it. Whereas tamoxifen works by blocking the effect of oestrogen on cancer cells, the new drug, known as an aromatase inhibitor, stops the production of the hormone altogether. This matters because in up to four-fifths of cases, oestrogen promotes the growth of tumours. Another aromatase inhibitor, Femara, is also undergoing trials to see if it is effective on early stage breast cancer, and should be producing results in 2004.
The ATAC (Arimidex, tamoxifen alone or in combination) trial conducted by University College Hospital in London showed that post-menopausal women who took Arimidex daily for two and a half years after surgery were 77 per cent less likely to suffer a relapse by developing cancer in the unaffected breast. Using tamoxifen over the same period reduced the risk by 54 per cent.
There is still some way to go, and many want to see evidence that over a five-year period this adjuvant therapy is as safe as tamoxifen; the data stretches to three years so far. It is not clear yet what cutting off the oestrogen tap altogether would do for a woman's bone density, or for her libido. However, the study suggests Arimidex also carries fewer side-effects than tamoxifen, reducing the risk of cancer of the womb lining (endometrial cancer).
One drug that has just won Nice's blessing is Herceptin, a drug that has been available in the US for the past five years. This works by targeting the HER2 gene, which is only present in around one-fifth of breast cancer patients but merits serious attention because it encourages cancer cells to spread more quickly. Herceptin is not a cure but can prolong life by as much as 10 months, and there has been outrage that it took Nice 18 months to sanction a treatment that had won its licence years ago.
Other large-scale trials underway are looking at whether the drugsTaxotere and Taxol can help women at an early stage of the disease. Both are known to prolong the lives of patients who have advanced breast cancer.
Several 'bolt-on' drugs that hold out the promise of reducing the risk of death by preventing the spread of the disease are also in the pipeline. Cancer cells, unlike normal cells, don't stop reproducing, and a tumour is made up of billions of cells that are copies of the original cancer cell. In the process, they can also lose the molecules that keep them sticking in the right place, and become detached from their neighbours, which enables them to spread through the bloodstream to different parts of the body.
One of the bolt-on drugs being studied is clodronate. A trial led by Professor Powles at the Royal Marsden Hospital showed that by reducing the loss of bone, the therapy could cut the risk of the cells spreading into the bones.
The trial, involving 1,069 women with breast cancer, showed that 23 per cent fewer patients receiving clodronate compared with those taking the placebo died over a follow-up period of five and a half years. While they took the drug, it halved the chances of cancer cells spreading into the bone.
Advances in genetic testing mean that, in the future, patients' individual DNA profiles are likely to influence clinicians' decisions on which drugs they should have. So far the powerful BRCA1 and BRCA2 genes have been identified to reveal those women at high risk of having the cancer, but these comprise only 5 per cent of all cases. There are some 80 or 90 other proteins in the body that have a part to play in the development of tumours, either by predisposing a woman to be more sensitive to oestrogen or to other environmental factors.
What is becoming increasingly clear is that women carry stark differences in their chances of developing the disease according to their DNA. An analysis published earlier this year of the incidence of breast cancer in the relatives of 1,484 women with the disease, carried out by scientists in Cancer Research UK's laboratories in Cambridge, found inherited risk is caused by lots of so-called 'soft' genes, each having a modest effect, rather than the small number of high-risk ones such as BRCA1. In fact, 88 per cent of cases occurred in 50 per cent of the women at highest risk from the soft genes.
Laboratories may one day be able to carry out swift genetic analysis on the cancer cells taken from tumours to predict with greater accuracy which patients are likely to develop secondary cancers, rather than bombarding everyone with the same therapies.
Dr Alison Jones, medical oncologist at the Royal Free Hospital in north London says: 'At the moment, chemotherapy is given to everyone as an insurance policy after surgery as a form of protection. If we could predict the most dangerous cancers, we could be far more selective about who needs to receive it. Now that's a really exciting prospect.'
