Key study points:
- Adjuvant tamoxifen for 10 years after diagnosis of early ER-positive breast cancer reduces recurrence and mortality compared to adjuvant tamoxifen for only 5 years.
- The main side effects were an increased risk of pulmonary embolism and endometrial cancer.
Primer: Breast cancers commonly express the estrogen receptor, and signaling through this receptor promotes tumor growth. Tamoxifen is a selective estrogen receptor modulator that inhibits estrogen signaling to tumor cells and can thereby inhibit tumor growth.
Tamoxifen is frequently given to premenopausal women, whereas postemenopausal women may receive aromatase inhibitors instead. Aromatase inhibitors block the production of estrogen in the body. This strategy is ineffective in premenopausal women because the reduction in estrogen levels stimulates gonadotropin secretion, which promotes estrogen synthesis and counteracts the effect of the aromatase inhibitor.
Adjuvant tamoxifen refers to the administration of tamoxifen after surgical removal of the primary tumor. Randomized trials have shown that adjuvant tamoxifen for 5 years is more effective than just 2 years. However, it is unclear whether adjuvant tamoxifen for more than 5 years provides additional benefit. The Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial compares relapse and mortality in women who received adjuvant tamoxifen for either 5 or 10 years.
This [randomized controlled] study: The ATLAS trial enrolled 12,894 women from over 30 countries with early breast cancer and who had already been taking tamoxifen for approximately 5 years. Half the women were randomized to stop tamoxifen (control group) and the other half were randomized to continue for another 5 years (treatment group). All women were followed for 10 years from trial entry.
Only those with known ER-positive disease (6846 women) were used to evaluate the main outcomes (mortality and recurrence). Continued tamoxifen reduced the risk of recurrence in the trial period from 25.1% to 21.4% (RR 0.84, 95% CI 0.76 – 0.94; p=0.002). Overall mortality was also reduced in the treatment group (639 deaths in 3428 women vs. 722 deaths in 3418 women, p=0.01)
Notable side effects were an increased risk of pulmonary embolism and endometrial cancer. On the other hand, a reduction in ischemic heart disease was observed in the treatment group.
In sum: Longer adjuvant tamoxifen treatment reduces recurrence and mortality in women diagnosed with early ER-positive breast cancers. Tamoxifen appears to confer some carryover benefit, as the greatest differences in recurrence and mortality between the two groups were observed in the 5 years after the treatment group had stopped taking tamoxifen.
The consensus appears to be that the benefits of extended tamoxifen found in this study outweigh the risks and monetary cost (see Background Reading and Editorial in The Lancet).
Future studies are likely to explore even longer regimens of tamoxifen.
By [TJ] and [MP]
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