Clinical Topics   /   Oncology

Extended Tamoxifen Treatment Lowers Recurrence, Deaths

By US Medicine

SAN ANTONIO – Longer is better when it comes to adjuvant treatment with tamoxifen for women with estrogen receptor-positive breast cancer.

That’s according to a recent study finding that, for those patients, continuing tamoxifen to 10 years instead of stopping at five years results in further reduction in recurrence and mortality, particularly after the 10th year. 1

“These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis,” according to the international Adjuvant Tamoxifen — Longer Against Shorter (ATLAS) study. It noted that longer therapy offered greater protection against late recurrence and death from breast cancer compared with the “current standard of five years of tamoxifen.”

The study, partly funded by the U.S. Army, was presented at the 2012 Cancer Therapy & Research Center-American Association of Cancer Research (CTRC-AACR) San Antonio Breast Cancer Symposium in December and simultaneously published in Lancet.

“Five years of adjuvant tamoxifen is already an excellent treatment that substantially reduces the 15-year risk for recurrence and death from estrogen receptor (ER)-positive breast cancer, but ATLAS now shows that 10 years of tamoxifen is even more effective,” said lead author Christina Davies, MD, a coordinator in the Clinical Trial Service Unit at the University of Oxford in Great Britain.

“The main additional benefit from continuing tamoxifen treatment is to reduce breast cancer mortality during the second decade after diagnosis,” Davies said. “We already knew that five years of tamoxifen reduces breast cancer mortality in this late period by almost 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.”

For the study, researchers enrolled 6,846 women with ER-positive breast cancer — half with node-positive disease — between 1996 and 2005. The women, who had been using tamoxifen for five years, were randomly assigned to continue treatment for another five years or to stop immediately.

With 1,328 breast cancer recurrences and 728 deaths after recurrence after about eight years of follow-up, length of treatment appeared to have little effect on either recurrence rates or death rates during the period five to nine years after diagnosis. During the second decade following diagnosis, however, the women who continued tamoxifen treatment had a 25% lower recurrence rate and a 29% lower breast cancer mortality rate compared with women who stopped after five years.

Overall, there was a 2.8% absolute gain, with risk for death from breast cancer five to 14 years after diagnosis, 12.2% with longer use compared with 15% for those who stopped after five years. The greatest benefit was during the 10- to 14-year time period after diagnosis, according to the researchers.

Longer-term tamoxifen use is not without risks, with endometrial cancer being the most dangerous potential side-effect. Because endometrial cancer is generally curable, however, that risk is heavily outweighed by the reduction in breast cancer deaths, Davies noted, adding that, in premenopausal women for whom tamoxifen is often the endocrine treatment of choice, there was no apparent excess of endometrial cancer.

“Many women with ER-positive breast cancer take tamoxifen, or some other adjuvant endocrine treatment, but the current recommendation is to stop after five years,” said Davies. “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.”

1. Davies C, Pan H, Godwin J, Gray R, et al. Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. 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 randomized trial. Lancet. 2012 Dec 4. doi:pii: S0140-6736(12)61963-1. 10.1016/S0140-6736(12)61963-1. [Epub ahead of print] PubMed PMID: 23219286.


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