Continuing Tamoxifen Beyond 5 Years May Reduce Recurrence and Mortality in Women with Estrogen Receptor-Positive Early Breast Cancer

DynaMed Weekly Update - Volume 7, Issue 50

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In women with estrogen receptor (ER)-positive early breast cancer, adjuvant tamoxifen treatment for 5 years has been associated with reduced recurrence and breast cancer mortality for up to 15 years compared to either no tamoxifen treatment or treatment for 1-2 years (Lancet 2011 Aug 27;378(9793):771). Tamoxifen for 5 years is recommended for premenopausal women with early breast cancer (New Zealand Guidelines Group 2009 Aug). The newly-published Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial evaluated whether continuing tamoxifen for an additional 5 years would further improve outcomes in a group of 12,894 women. Previous smaller trials have not shown a benefit of such extended tamoxifen treatment.

In the ATLAS trial, women with early breast cancer who had completed 5 years of tamoxifen treatment were randomized without blinding to continued tamoxifen (20 mg/day) for a total 10 years vs. immediate stopping of tamoxifen treatment. ER status was positive in 53% (6,846 women), negative in 10% and unknown in 37%. Women were excluded at clinician discretion for any contraindication to continued tamoxifen. In the 10-year treatment group, treatment could be stopped for emergent definite contraindications and it could be restarted in the 5-year treatment group for definite indication. At publication, 91% had completed 10 years follow-up and 77% had completed 15 years follow-up. The adherence rates in the 10-year treatment group were 84% at 7 years and < 60% at 10 years.

In the prespecified subgroup of ER-positive women, the rates of breast cancer recurrence were 18% with 10-year tamoxifen treatment vs. 20.8% with 5-year treatment (p = 0.002, NNT 36) (level 2 [mid-level] evidence). Tamoxifen for 10 years was associated with reductions in both breast cancer mortality (9.66% vs. 11.6%, p = 0.01, NNT 52) and all-cause mortality (18.6% vs. 21.1% (p = 0.01, NNT 40). The benefits of continued treatment for both recurrence and mortality were significant at ≥ 10 years follow-up, but not at 5-9 years follow-up. There were no significant differences in mortality in analysis of women with ER-negative status or unknown ER status.

The risks of other adverse outcomes occurring prior to recurrence were analyzed in all women regardless of ER status. Continued tamoxifen treatment was associated with increased risk of endometrial cancer (event rate ratio 1.74, 95% CI 1.3-2.34) and pulmonary embolism (event rate ratio 1.87, 95% CI 1.13-3.07), and decreased risk of ischemic heart disease (event rate ratio 0.76, 95% CI 0.6-0.95). There was no significant difference in the rates of endometrial cancer-related death (Lancet 2012 Dec 4 early online).

For more information, see the Endocrine therapy for breast cancer topic in DynaMed.