Twenty-five–year results of a Swedish study found that 2 years of adjuvant tamoxifen provides a long-term survival benefit in premenopausal women with estrogen receptor–positive breast cancer.
Twenty-five–year results of a Swedish study found that 2 years of adjuvant tamoxifen provides a long-term survival benefit in premenopausal women with estrogen receptor (ER)-positive breast cancer, in particular with regard to breast cancer-related mortality, when compared to a control group that received no systemic therapy.
The SBII:2pre trial was conducted in Sweden between 1984 and 1991, and in 2005 results showed a recurrence-free survival benefit with 2 years of tamoxifen and some indication that overall survival curves might be separating over time. “The carryover effect, indicating that the efficacy of the drug remains after cessation of treatment, has been observed in several studies with extended follow-up,” wrote study authors led by Maria Ekholm, MD, of Lund University in Lund, Sweden.
The original trial included 564 premenopausal women with primary breast cancer, randomized to either 2 years of adjuvant tamoxifen (276 patients) or no systemic treatment (288 patients). Of those, 250 patients remained alive in April 2014, and the median follow-up for those patients was 26.3 years. The results were published online ahead of print in the Journal of Clinical Oncology.
Of the 314 deaths among participants, 262 were categorized as breast cancer related. The unrelated deaths were generally well balanced between the two groups, with the exception of eight cardiac-related deaths, all found in the tamoxifen group.
There was a non-significant trend toward a cumulative mortality benefit with tamoxifen in all patients, with a hazard ratio (HR) of 0.82 (95% CI, 0.66–1.02; P = .080). For cumulative breast cancer-related mortality, the HR was 0.81 (95% CI, 0.64–1.03; P = .090).
Specifically in the 362 patients with ER-positive tumors, tamoxifen yielded a bigger survival advantage. In those patients, the HR for cumulative mortality was 0.77 (95% CI, 0.58–1.03; P = .075), but the HR for breast cancer-related mortality was significant, at 0.73 (95% CI, 0.53–0.99; P = .046). A significant positive effect of tamoxifen was also found in those with ER-positive, progesterone receptor (PR)-positive tumors, but not in those with ER-negative, PR-negative tumors.
Tamoxifen offered the most benefit in ER-positive patients who were younger than 40 years at diagnosis. In those patients, the HR for cumulative mortality was 0.45 (95% CI, 0.23–0.91), and in those 40 years and older it was 0.89 (95% CI, 0.65–1.23). Histologic grade 3 disease was also associated with a greater benefit with tamoxifen.
The effects of the drug on survival varied over time. There was no significant benefit out to year 5, and from 15 years and after, but from year 5 to year 15 the HR for cumulative mortality was 0.58 (95% CI, 0.37–0.91; P = .018). The same was true for cumulative breast cancer-related mortality.
“The long-term effect reported in this study is particularly important for young patients with a potentially long life expectancy who are at risk for late relapse, as is commonly seen in ER-positive breast cancer,” the authors concluded.