Clinical Question: Does exemestane therapy improve outcomes in patients who have breast cancer when begun two to three years after diagnosis?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (double-blinded)

Synopsis: Tamoxifen is the current standard of care for the treatment of estrogen-receptor–positive breast cancer in postmenopausal women. Exemestane is an aromatase inhibitor that blocks the conversion of androgens to estrogen and may be superior to tamoxifen in patients with metastatic disease.

After two to three years of tamoxifen therapy, patients were randomized to receive exemestane in a dosage of 25 mg daily (n = 2,380) or tamoxifen in a dosage of 20 mg daily (n = 2,362) to complete a five-year course of therapy. All of the women were postmenopausal, had normal renal and liver function, and had an estrogen-receptor–positive primary breast cancer. Allocation was concealed, and analysis was by intention to treat. Patients were reevaluated regularly. The primary outcome was disease-free survival.

The number of patients with death, contralateral breast cancer, or recurrence was lower in the exemestane group (183 versus 266 in the tamoxifen group; 7.8 percent versus 11.2 percent; P < .001). After three years, the likelihood of disease-free survival was 91.5 percent in the exemestane group and 86.8 percent in the tamoxifen group (absolute risk reduction = 4.7 percent; number needed to treat for three years = 21.3).

Fewer deaths occurred in the exemestane group, but this difference was not statistically significant (93 versus 106 in the tamoxifen group). The risk of contralateral breast cancer was lower in the exemestane group (hazard ratio = 0.44; 95 percent confidence interval, 0.20 to 0.98). Use of exemestane caused more arthralgias and episodes of diarrhea but fewer thromboembolic events, less vaginal bleeding, and less muscle cramping than tamoxifen.

Bottom Line: Exemestane improves outcomes for postmenopausal women with estrogen-receptor–positive breast cancer when given for two to three years after a two- to three-year course of treatment with tamoxifen. (Level of Evidence: 1b)