Hopes that new breast cancer drugs might save thousands more lives were raised again last night with the publication of further promising evidence to suggest they outshine tamoxifen, the long-established gold standard treatment that has revolutionised treatment of early breast cancer since the 1980s.
A big study of more than 8,000 women, comparing results among those given one of the new drugs - letrozole - after surgery, and those given tamoxifen, reports particularly impressive results among women with a high chance of breast cancer returning. Among women whose breast cancer had spread to their lymph nodes, there were 29% fewer cases of cancer returning in those on letrozole, and among those who had also needed chemotherapy, there were 28% fewer cases of returning cancers.
In all the women taking letrozole, marketed as Femara by drug company Novartis, there was a 19% reduction in the risk of cancer returning and a 27% reduction in it having spread to other parts of the body. Trials involving close to 30,000 women have now shown big improvements following treatment with a drug from the new class called aromatase inhibitors, either alone or after tamoxifen. Other drugs in the group include anastrozole and exemestane.
Questions remain about which new drug is best for which patients, whether tamoxifen should still play a role, and in which sequence drugs should be given. There are also concerns that women on the new drugs might be at greater risk of cardiovascular problems, bone fractures and joint pain, although there are fewer instances of uterine cancer and blood clots compared with women on tamoxifen.
These are among issues that will be considered by advisers to the NHS in England and Wales, who must determine the effectiveness and value-for-money of the new drugs. Their verdict is expected in November next year, but the flood of good news from trials involving the aromatase inhibitors may lead to pressure on doctors to prescribe them, and local health trusts to fund them, in the way that there have been calls to fund Herceptin, a drug aimed at a different and particularly aggressive form of breast cancer.
Around four in five of the 41,000 women diagnosed with breast cancer in Britain each year have passed the menopause, and three-quarters of those might be suitable for treatment with an aromatase inhibitor because they have tumours fuelled by oestrogen. Tamoxifen, which reduces the risk of cancer returning by about half, works by stopping oestrogen stimulating cancer cells, while the aromatase inhibitors block an enzyme that manufactures oestrogen.
The new results for letrozole were published in the New England Journal of Medicine by the Breast International Group, a global coordinating body.
They come from a study of more than 8,000 women in 29 countries, including more than 400 in 11 centres in Britain. Women were enrolled between March 1998 and May 2003 to start a five-year course of treatment, on letrozole alone, letrozole followed by tamoxifen after two years, tamoxifen alone and tamoxifen followed by letrozole after two years.
Among the 4,003 women taking letrozole, there were 351 cases of cancer returning, while there were 428 among the 4,007 in the tamoxifen trials. Among the women where the breast cancer had included their lymph nodes, just over 40% of all involved, and in the 25% who had needed chemotherapy, the results for letrozole over tamoxifen were better - 29% and 28% fewer cases respectively.
In an accompanying editorial, Sandra Swain, of the National Cancer Institute, in Bethesda, Maryland, said experts were now trying to classify breast cancers into multiple categories. "It is essential to define each subgroup precisely and delineate distinct characteristics and targets that will lead us to tailored therapies that are better than the ones we have now."
Backstory
Hormone treatments such as tamoxifen introduced more than 20 years ago are a factor in improving survival rates for breast cancer. Most women newly diagnosed with tumours stimulated to grow by oestrogen are prescribed the drug for five years. It has proved a simple, safe and reliable treatment. Alternatives such as aromadase inhibitors have been around for some years but their first target was in women with breast cancer that had spread. Attention shifted in the 1990s towards seeing whether they could also lower the number of women whose cancer returned after surgery. Trials have compared the performance of individual drugs in the class, anastrozole (Arimidex), exemestane (Aromasin) and letrozole (Femara) with tamoxifen. Results are so encouraging Cancer Research UK has suggested the place of tamoxifen in cancer care should be reassessed.
