Tamoxifen For 10 Years Is Better Than The Current Standard Of 5 Years According To The ATLAS Trial

 

Tamoxifen For 10 Years Is Better Than The Current Standard Of 5 Years According To The ATLAS TrialLong-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

Summary

Background

For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years.

Methods

In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12 894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633.

Findings

Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0•002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0•01), and reduced overall mortality (639 deaths vs 722 deaths, p=0•01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0•90 [95% CI 0•79—1•02] during years 5—9 and 0•75 [0•62—0•90] in later years; breast cancer mortality RR 0•97 [0•79—1•18] during years 5—9 and 0•71 [0•58—0•88] in later years). The cumulative risk of recurrence during years 5—14 was 21•4% for women allocated to continue versus 25•1% for controls; breast cancer mortality during years 5—14 was 12•2% for women allocated to continue versus 15•0% for controls (absolute mortality reduction 2•8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12 894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0•99 [0•89—1•10]; p=0•84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1•87 (95% CI 1•13—3•07, p=0•01 [including 0•2% mortality in both treatment groups]), stroke 1•06 (0•83—1•36), ischaemic heart disease 0•76 (0•60—0•95, p=0•02), and endometrial cancer 1•74 (1•30—2•34, p=0•0002). The cumulative risk of endometrial cancer during years 5—14 was 3•1% (mortality 0•4%) for women allocated to continue versus 1•6% (mortality 0•2%) for controls (absolute mortality increase 0•2%).

Interpretation

For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. 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.

Funding

Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.

Dr. Chris’s Take:

This was perhaps the most important study presented at the 2012 San Antonio Breast Conference. This study was also published in the British cancer journal The Lancet. Patient’s whose breast cancer is fed by estrogen and are premenopausal most likely will be prescribed tamoxifen which is a drug that blocks the estrogen receptors on breast cancer cell and leads to the death of the cancer cell. This has clearly reduced the likelihood that cancer will return either in the breast or somewhere else in the body. The normal duration of tamoxifen is 5 years but the ATLAS study above confirms that 10 years of treatment will reduce the return of breast cancer by nearly 4%. Lengthening tamoxifen to 10 year may not be for everyone as side effect such as blood clots, uterine cancer were increased in this study. I would favor this to be a good option for patients with higher risk breast cancer such as large size, lymph node involvement and higher grades. This data does not apply to the aromatase inhibitors such as femara (letrozole), arimidex (anastrozole) or aromasin (exemestane) which are commonly used for post-menopausal patients with estrogen fed cancers. The standard duration for these drugs is still 5 years. Ask your doctor if extending tamoxifen to 10 years if the correct treatment for you.

Resources: 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

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris was born in Europe but has lived in the US for many years. He attended college both in Europe and the US and completed medical school at the University of Texas. Residency and fellowship in oncology was completed at Baylor. Read More...
Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton