Ten years of adjuvant tamoxifen treatment further reduces breast cancer recurrence and improves survival

December 05, 2012

Tamoxifen is widely used for treating ER-positive breast cancer [1], and is usually given daily for 5 years after the cancer has been removed surgically. This substantially reduces the breast cancer mortality rate not only while treatment continues, but throughout the first 15 years after diagnosis. It is known that 5 years is more effective than just 2 years of tamoxifen, but it was not known whether continuing beyond 5 years would produce a further reduction in 15-year breast cancer mortality.

In the ATLAS trial, an international group of researchers, led by Dr Christina Davies of the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) at the University of Oxford, UK, examined whether continuing treatment with tamoxifen for ten years resulted in any further reduction in breast cancer mortality, in comparison with stopping tamoxifen treatment after only five years. They also assessed the additional side-effects resulting from longer-term use of tamoxifen.

For the analysis of side-effects, the researchers studied 12 894 women who had received tamoxifen for five years at the start of the study, regardless of whether or not those women had ER-positive disease. However, as tamoxifen's main protective effect is only against ER-positive breast cancer, the researchers restricted their analyses of the effects on recurrence and breast cancer mortality to the 6847 women with definitely ER-positive disease. Of these women, 3428 were randomly allocated to continue tamoxifen treatment for a further five years (ie, to ten years of treatment in total), and 3418 were allocated, as the control group, to stop tamoxifen immediately (ie, after only five years of treatment).

The researchers found that continuing tamoxifen for ten years rather than stopping at 5 years further reduced rates of recurrence and breast cancer mortality, but that the additional benefits took some years to emerge. Starting from entry to the trial at year 5, the risk of recurrence by year 15 was 21.4% in those allocated to continue tamoxifen, compared to 25.1% in the control group. Breast cancer mortality during years 5-15 was also significantly reduced, being 12.2% in those allocated to continue tamoxifen compared with 15.0% in the control group.

Although tamoxifen has some side-effects, their net effects on survival were relatively small, the most significant being an increased risk among post-menopausal women of developing cancer of the lining of the womb (endometrial cancer). This is, however, generally curable, and the excess risk of dying by year 15 of endometrial cancer was only 0.2% (0.4% in the group allocated to continue tamoxifen compared with 0.2% in the control group). The researchers found no evidence for an increased risk of stroke during treatment with tamoxifen, despite the fact that the US Food and Drug Administration (FDA) lists this as a possible side-effect of the drug.

According to Dr Davies, "Our results, taken together with results from previous trials of 5 years of tamoxifen versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. Good evidence now exists that 10 years of tamoxifen in ER-positive breast cancer produces substantial reductions in rates of recurrence and in breast cancer mortality not only during the first decade, while treatment continues, but also during the second decade, long after it has ended."

"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." [3]

Writing in a linked Comment, Professor Trevor Powles of the Cancer Centre London, UK, welcomes the results, adding "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." [3]

[1] ER-positive cancer is driven by the female sex hormone oestrogen, and tamoxifen blocks this effect.

[2] The mission of the 2012 CTRC-AACR San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR) and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR's scientific prestige in basic, translational and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit www.sabcs.org.

[3] Quotes direct from authors and cannot be found in text of Article / Comment.


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