Fan Y, Sun T, Shao Z, et al. - This randomized clinical trial (MIRACLE) demonstrates the effectiveness of everolimus (mammalian target of rapamycin inhibitor) plus letrozole as first-line therapy for premenopausal patients with selective estrogen receptor modulator (SERM)-resistant, hormone receptor (HR)-positive, ERBB2-negative advanced breast cancer.

• Participants were premenopausal women with HR-positive, ERBB2-negative advanced breast cancer who faced disease progression while taking SERMs.

• 199 women were randomized in a 1:1 ratio to receive everolimus (10 mg orally once daily) plus letrozole (2.5 mg orally once daily) (n = 101) or letrozole alone (2.5 mg orally once daily) (n = 98).

• Everolimus plus letrozole provided significantly longer progression-free survival than letrozole alone in premenopausal patients with HR-positive/ERBB2-negative advanced breast cancer (19.4 months vs 12.9 months; hazard ratio, 0.64).

• Effectiveness of everolimus was evident even among patients taking treatment with the same endocrine agent post- disease progression.