Ten years of tamoxifen treatment can approximately halve the number of deaths from the most common form of breast cancer during the second decade after diagnosis, according to the results of the Cancer Research UK- funded ATLAS trial published in the Lancet today (Wednesday).
Around three-quarters of women with breast cancer in the UK are diagnosed with oestrogen-receptor positive (ER+) disease, which is driven by the female hormone, oestrogen. After any surgery, radiotherapy or chemotherapy, many women receive some years of endocrine treatment with a drug like tamoxifen or with an aromatase inhibitor, to prevent any remaining cancer cells being ‘re-fuelled’ by oestrogen.
Tamoxifen taken daily for five years – the current standard duration of treatment – is already known to reduce death rates by around a third throughout the first 15 years after diagnosis, as the protective effects continue for at least a decade after the five years of treatment has ended.
The new trial investigated whether continuing to take tamoxifen for a total of 10 years would reduce the breast cancer death rate still further.
The international ATLAS study, also co-funded by the Medical Research Council, recruited nearly 7,000 women with ER+ breast cancer who were completing five years of tamoxifen treatment. They were randomly allocated, half to stop treatment immediately and half to continue for five more years. All were followed for an average of another eight years.
Initially there was little difference in outcome from the two groups, because throughout the first decade both groups were protected by the first five years of treatment. But, after year 10 the additional benefits of longer treatment emerged in the group that continued taking tamoxifen. Among them, the risk of dying during the second decade from breast cancer was further reduced by about a quarter – on top of the substantial benefits due to the first five years of treatment.
Most of the extra protection from taking the drug for longer occurred after the end of the 10-year treatment period.
Dr Christina Davies, a Cancer Research UK scientist at Oxford University and leader of the ATLAS study, said: “Around three-quarters of all UK women with breast cancer have hormone sensitive disease, and ATLAS shows that 10 years of tamoxifen helps save lives not just during the decade women are taking the drug, but also during the second decade after diagnosis.”
In post-menopausal women tamoxifen increases the risk of endometrial – or womb – cancer. The ATLAS results showed that the extra risk of dying from this disease was two per thousand women who took tamoxifen for five years, and four per thousand women who took tamoxifen for 10 years. The reduction in the numbers of deaths from breast cancer after 10 years of tamoxifen was about 30 times as great as this increase in the numbers of endometrial cancer deaths.
Cancer Research UK is a major funder of breast cancer research in the UK. Our research has contributed to developing treatments that mean that eight out of 10 women now survive their breast cancer for more than five years, compared with five out of 10 women in the 1970s. And 64 per cent of women now survive their breast cancer for at least 20 years.
Martin Ledwick, Cancer Research UK’s head information nurse, said: “This important study adds further clarity to the question about the length of time women should take tamoxifen. Although treatment for hormone receptor positive breast cancer has become more complex in recent years with some women receiving aromatese inhibitors, these results will help in deciding the length of treatment for women who are prescribed tamoxifen alone.”
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Long term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Davies et al. Lancet 5 December 2012 DOI: 10.1016/S0140-6736(12)61963-1
The researchers studied 12,894 women with breast cancer who were just completing about five years of tamoxifen treatment, of whom 1248 had ER-negative disease, 4800 had untested ER status and 6846 had ER+ disease. The reduction in death rate was calculated using data from the women with oestrogen-positive disease.
Of the 6846 women with oestrogen positive disease, 3418 were allocated to stop taking tamoxifen after five years, while 3428 were allocated to continue their tamoxifen treatment for a further five years (ie, for a total of ten years).
It is estimated that in Great Britain between 65 per cent and 85 per cent of breast cancers in women are oestrogen receptor positive. This range has been applied to the UK incidence figure (49,564). (Source: National Cancer Intelligence Network (2011): Second All Breast Cancer Report.)