Is anastrozole really better than tamoxifen for low-risk breast cancer?

[OBJECTIVE] In 2002, the ATAC trial (Arimidex, Tamoxifen, Alone or in Combination) established anastrozole as the preferred adjuvant treatment over tamoxifen in postmenopausal women (disease-free survival at 89.4 ​% vs. 87.4 ​%) with hormone receptor-positive breast cancer (BC). The efficacy demonstrated in the ATAC trial led to the broader adoption of aromatase inhibitors in younger women. This practice necessitates using GnRH agonists or ovarian ablation to induce menopause, which causes significant side effects such as bone deterioration. Our study aimed to compare local recurrence (LR) and overall survival (OS) between anastrozole and tamoxifen for low Oncotype Recurrence Scores (RS). We hypothesize that there is little to no difference in LR and OS between the two medications in both pre- and postmenopausal women.

[METHODS] The TriNetX database was used to create retrospective cohort studies based on low (0-17) Oncotype RS. We conducted two studies comparing women <50 or >50 years old who were treated with either anastrozole or tamoxifen. All studies excluded Stage 4 or T4 tumors and had propensity scores matched by age, tumor stage, tumor size (T), and nodal status (N). Outcomes of interest were 10-year OS and LR.

[RESULTS] For patients aged >50, there were 1734 patients on anastrozole and 682 on tamoxifen, with 582 patients per cohort after matching. Within 10 years, 10 or fewer patients died, with no statistically significant difference in 10-year OS (KM analysis: 98 ​% vs. 97 ​%, p ​= ​0.6). LR was 7.2 ​% in the anastrozole group and 7.6 ​% in the tamoxifen group, with no statistically significant difference (HR 1, 95 ​% CI, 0.69-1.65). For patients aged <50, 94 received anastrozole and 270 received tamoxifen, with 82 matched patients included in the analysis. Within 10 years, no patients died, and 10 or fewer experienced LR. There was no significant difference in both 10-year OS (KM analysis: 100 ​% vs. 100 ​%, p ​= ​1) and LR (12 ​% vs. 12 ​%, HR 2, 95 ​% CI, 0.59-6.56).

[CONCLUSIONS] In both pre- and postmenopausal women, there is no difference in 10-year OS or LR between anastrozole and tamoxifen for BC patients with low Oncotype RS. We conclude that Stage 1-3, T1-T3 pre- and postmenopausal BC patients with Oncotype RS between 0 and 17 can safely choose either medication. This finding is of particular importance for premenopausal women who wish to avoid the adverse side effects of medically induced menopause and bone deterioration associated with the anastrozole and ovarian suppression approach.