Tamoxifen for 10 years may halve breast cancer mortality during the second decade after diagnosis

Continuing tamoxifen for 10 years rather than stopping at five years reduces recurrence and mortality in estrogen receptor-positive early breast cancer, particularly after year 10, a study found.

To assess the effects of continuing tamoxifen to 10 years instead of stopping at five years, researchers looked at data from nearly 13,000 women enrolled globally in the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial. Women with early breast cancer who had completed five years of treatment with tamoxifen were randomized 1:1 to continue tamoxifen to 10 years or stop treatment.

Results appeared online Dec. 5 at The Lancet.

Among women with estrogen receptor-positive early breast cancer, 10 years of treatment with tamoxifen reduced:

• the risk of breast cancer recurrence (617 recurrences in 3,428 women allocated to continue vs. 711 recurrences in 3,418 controls, P=0.002),
• breast cancer mortality (331 deaths vs. 397 deaths, P=0.01), and
• overall mortality (639 deaths vs. 722 deaths, P=0.01).

Researchers noted that reductions in adverse breast cancer outcomes appeared to be less extreme in the first decade of treatment compared to the second decade. The recurrence rate ratio (RR) during years five to nine was 0.90 (95% CI, 0.79 to 1.02) compared to 0.75 (95% CI, 0.62 to 0.90) after 10 years. The breast cancer mortality RR was 0.97 (95% CI, 0.79 to 1.18) during years five to nine and 0.71 (95% CI, 0.58 to 0.88) after 10 years. The cumulative risk of recurrence during years five to 14 was 21.4% for women allocated to continue versus 25.1% for controls. Breast cancer mortality during years five to 14 was 12.2% for women allocated to continue versus 15% for controls (absolute mortality reduction, 2.8%).

Treatment allocation seemed to have no effect on breast cancer outcomes among 1,248 women with estrogen receptor-negative disease and an intermediate effect among 4,800 women with unknown estrogen-receptor status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was similar in both groups (691 deaths without recurrence in 6,454 women allocated to continue versus 679 deaths in 6,440 controls; RR, 0.99; 95% CI, 0.89 to 1.10; P=0.84).

Researchers noted that this study, taken together with results from previous trials, suggest that 10 years of tamoxifen can approximately halve breast cancer mortality during the second decade after diagnosis.

There are side effects to note, researchers wrote. Tamoxifen increased the incidence of endometrial cancer in postmenopausal women who had not had a hysterectomy. Although there is little risk in premenopausal women, risk calculation shows that five years of adjuvant tamoxifen carries an absolute 15-year endometrial cancer risk of about 2% to 3%, and that 10 years is associated with an additional 2% risk by year 15. However, the death rate from endometrial cancer is about one-tenth of the incidence rate, so the excess of uterine cancer mortality is greatly outweighed by the decrease in breast cancer mortality, the authors said.

An editorial noted that other trials of tamoxifen are still under way, and a meta-analysis of all trials could result in changing the standard of care to 10 years of tamoxifen. “This change should open up a whole new era of clinical trials to assess the benefit of extended adjuvant endocrine therapy of breast cancer,” the editorialist wrote.