Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials.

BACKGROUND: Several trials have been done to assess treatment of premenopausal breast cancer with luteinising-hormone-releasing hormone (LHRH) agonists, but results have been inconclusive, especially for patients with hormone-receptor-positive cancer.
METHODS: We collected individual patients' data from published trials and did analyses focused on women with tumours positive for oestrogen receptor, progesterone receptor, or both. The main endpoints were recurrence and death after recurrence.
FINDINGS: We obtained data for 11 906 premenopausal women with early breast cancer randomised in 16 trials. When used as the only systemic adjuvant treatment, LHRH agonists did not significantly reduce recurrence (28.4% relative reduction, 95% CI consistent with 50.5% reduction to 3.5% increase, p=0.08) or death after recurrence (17.8%, 52.8% reduction to 42.9% increase, p=0.49) in hormone-receptor-positive cancers. Addition of LHRH agonists to tamoxifen, chemotherapy, or both reduced recurrence by 12.7% (2.4-21.9, p=0.02); and death after recurrence by 15.1% (1.8-26.7, p=0.03). LHRH agonists showed similar efficacy to chemotherapy (recurrence 3.9% increase, 7.7% reduction to 17.0% increase; death after recurrence 6.7% reduction, 20.7% reduction to 9.6% increase; both not significant). No trials had assessed an LHRH agonist versus chemotherapy with tamoxifen in both arms. LHRH agonists were ineffective in hormone-receptor-negative tumours.
INTERPRETATION: LHRH agonists provide an additional class of agents for treatment of premenopausal women with hormone-receptor-positive breast cancer. Optimum duration of use is unknown.