Taking tamoxifen for ten years following breast cancer surgery rather than five is more effective and better at reducing the risk of recurrence and death, according to a recent trial led by Oxford University’s Clinical Trial Service Unit (CTSU), called ATLAS.

The findings, published online in The Lancet, explain how tamoxifen is able to suppress the effect that the female sex hormone estrogen has in causing estrogen receptor positive (ER-positive) breast cancer.

Lead investigator, Dr Christina Davies of Oxford University, said:

“Five years of adjuvant tamoxifen is already an excellent treatment that substantially reduces the 15-year risk for recurrence and death from ER-positive breast cancer, but ATLAS now shows that 10 years of tamoxifen is even more effective.”

After ER-positive breast cancer surgery to remove tumors, tamoxifen is usually recommended daily for five years. Tamoxifen works very well at lowering breast cancer mortality rate and at reducing the chance of recurrence.

Tamoxifen has been long used for the treatment of females with early-stage breast cancer, although a separate class of drugs, called aromatase inhibitors, has emerged in recent years as the preferred option.

Dr Christina Davies adds “ATLAS showed that protection against breast cancer recurrence and death is greater with 10 years than with five years of tamoxifen use. Women and their doctors should be aware of this evidence when deciding how long to continue tamoxifen, or any other endocrine treatment.”

The trial examined the benefits of continuing with tamoxifen for ten years, as well as looking at potential side effects. 6,846 women who had ER-positive breast cancer surgery were involved in the study between 1996 and 2005. They were either assigned to continue the use of tamoxifen after five years or told to stop. At the end of the eight year follow up period 1,328 of the women developed breast cancer again and 728 died.

Compared to those who stopped taking tamoxifen after five years, the breast cancer mortality rate of those who continued to use it for ten years was almost one quarter less.

For those who took tamoxifen for ten years the risk of death from breast cancer 10 to 15 years after diagnosis was 6.4% compared to 9.0% for those who only took it for 5 years.

It is vital that women with ER-positive breast cancer and their doctors know about this finding as tamoxifen is currently only used for five years.

Dr Davies said:

“The main additional benefit from continuing tamoxifen treatment is to reduce breast cancer mortality during the second decade after diagnosis,’ Dr Davies says. ‘We already knew that five years of tamoxifen reduces breast cancer mortality in this late period by about a third in comparison with no tamoxifen. We now know that 10 years of tamoxifen is even better, approximately halving breast cancer mortality during the second decade after diagnosis.”

Although using tamoxifen for an additional five years can also mean more side-effects, the study shows that the risks are small compared to the benefits. The most serious side effect associated with tamoxifen is an increase in the risk of developing endometrial cancer, the most common form of uterine cancer, in post-menopausal women.

Dr Davies adds “While our results show a small increase in life-threatening side-effects for women who take tamoxifen for ten years rather than five, this increase is greatly outweighed by the reduction in breast cancer mortality. Moreover, these side-effects cause little or no risk in pre-menopausal women with ER-positive disease, and if tamoxifen prevents the death of a pre-menopausal woman, then she could well gain several decades of life expectancy.”

The US Food and Drug Administration says that there is an increased risk of stroke associated with the use of tamoxifen, but the researchers in ATLAS did not find any evidence to support this.

According to Professor Trevor Powles of Cancer Centre London, “If, as seems likely, the ATLAS findings will be reinforced next year, this should herald a change of practice, with the standard of care revised to 10 years rather than 5 years of treatment in patients for whom tamoxifen is indicated.”

Experts say these finding will most likely not bring any drastic changes to medical practice, because the patients who were involved in this study were recruited nearly twenty years ago. Today, aromatase inhibitors have proved superior among older women with early-stage ER-positive cancer.

These results will be relevant for younger women (premenopausal) who are not considered candidates for aromatase inhibitors because of their side effects, and are typically prescribed tamoxifen.

The study was funded by the European Union, Cancer Research U.K., the US Army, the Medical Research Council (United Kingdom), and AstraZeneca.

Written by Joseph Nordqvist