Aromatase inhibitors have shown increased efficacy compared with tamoxifen in postmenopausal early breast cancer. This RCT assessed the efficacy and safety of anastrozole versus tamoxifen in premenopausal women (ER-positive, HER2-negative, operable disease with WHO performance status ≤2) receiving goserelin for early breast cancer in the neoadjuvant setting.

The study randomised 197 patients to goserelin 3•6 mg/month plus either anastrozole 1mg per day and tamoxifen placebo (n= 98) or tamoxifen 20mg per day and anastrozole placebo (n= 99) for 24 weeks before surgery. The primary endpoint was best overall tumour response (complete response or partial response), assessed by callipers, during the 24-week neoadjuvant treatment period for the intention-to-treat population. The primary endpoint was analysed for non-inferiority (i.e. lower limit of 95% CI for difference in overall response rates between groups ≤10%); in the event of non-inferiority, the superiority of the anastrozole group versus the tamoxifen group was assessed.

The findings of the primary analysis are published in the Lancet; treatment will also continue in the adjuvant setting for 5 years.

The following findings were reported:

• 185 patients completed the 24-week neoadjuvant treatment period and had breast surgery (95 anastrazole, 90 tamoxifen).

• More patients in the anastrozole group had a complete or partial response than did those in the tamoxifen group during 24 weeks of neoadjuvant treatment (anastrozole 70.4% [69 of 98] vs. tamoxifen 50.5% [50 of 99]; estimated difference between groups 19.9%, 95% CI 6.5 to 33.3; p=0.004).

• Treatment-related grade 3 adverse events were noted in 2 patients on anastrozole (arthralgia and syncope) and 1 patient on tamoxifen (depression).

• One serious adverse event was reported in the anastrozole group (benign neoplasm, not related to treatment), compared with none in the tamoxifen group.

The researchers suggest from these findings that “given its favourable risk-benefit profile, the combination of anastrozole plus goserelin could represent an alternative neoadjuvant treatment option for premenopausal women with early-stage breast cancer.”

According to an accompanying Comment article, although the study findings are interesting, the fundamental question about the value of ovarian suppression plus an aromatase inhibitor in premenopausal women remains unanswered. The study was underpowered to provide meaningful long-term outcome data and the clinical significance of modest short-term gains in clinical response in premenopausal women in the preoperative endocrine setting remains unknown. It notes that studies in progress, such as the Tamoxifen and Exemestane Trial (TEXT) and the Suppression of Ovarian Function Trial (SOFT), might provide further much needed data, but until then, ovarian suppression plus an aromatase inhibitor for (neo)-adjuvant therapy in premenopausal patients should only be given in the context of a clinical trial.