Aromatase Inhibitors May Reduce Recurrence Risk in Premenopausal Breast Cancer Over Tamoxifen

Treatment with an aromatase inhibitor appears to reduce the risk of breast cancer recurrence in patients who are premenopausal and undergoing ovarian suppression vs tamoxifen.

Aromatase inhibitors may reduce the risk of disease recurrence in patients with premenopausal breast cancer who are receiving ovarian suppression compared with tamoxifen (Soltamox; RR, 0.79; 95% CI, 0.69-0.90; P = .0005), according to findings from an analysis published in Lancet Oncology.

The most notable benefit was observed in years 0 to 4 (RR, 0.68; 99% CI, 0.55-0.85; P <.0001), with investigators highlighting a 3.2% (95% CI, 1.8%-4.5%) absolute reduction in 5-year recurrence risk. In years 5 to 9 (RR, 0.98; 99% CI, 0.73-1.33; P = .89) and 10 or higher, investigators did not observe any further benefit, or loss of benefit.

Investigators identified 4 randomized clinical trials that were conducted prior to January 1, 2010, that featured patients with estrogen receptor (ER)–positive, operable breast cancer who were randomized to receive either an aromatase inhibitor and ovarian suppression or tamoxifen and ovarian suppression. Studies included the phase 3 TEXT study (NCT00066703), assessing triptorelin (Trelstar) plus exemestane (Aromasin) or tamoxifen in premenopausal patients with hormone-responsive disease; the phase 3 SOFT trial (NCT00066690), examining ovarian suppression plus tamoxifen or exemestane vs tamoxifen alone in hormone-responsive breast cancer; the phase 3 HOBOE trial (NCT00412022), assessing adjuvant triptorelin and tamoxifen/letrozole, or letrozole and zoledronic acid (Reclast) in premenopausal patients; and the phase 3 ABCSG XII study (NCT00295646).

Primary outcomes included invasive disease recurrence, including distant, locoregional, or new primary; breast cancer mortality; death without recurrence, and all-cause mortality. Data were gathered from 7230 premenopausal patients who underwent treatment from June 17, 1999, to August 4, 2015, 97.2% of whom were included in the report. In addition to having ER-positive tumors, 60.2% of patients had node-negative disease. Patients included in the SOFT, TEXT, and HOBOE trials received either 5 years of treatment with an aromatase inhibitor or tamoxifen, and those in the ABCSG XII underwent 3 years of treatment.

Of the patients included in the analysis, 12.6% experienced disease recurrence and 5.9% died, with most deaths being due to causes unrelated to disease and without the presence of disease recurrence (12.9%). The median follow up across all trials was 8.0 years.

Additional findings indicated that the 10-year recurrence rate was 14.7% in the aromatase inhibitor cohort compared with 17.5% in the tamoxifen cohort. A reduction in distant recurrence was also reported in the aromatase group compared with the tamoxifen group (RR, 0.83; 95% CI, 0.71-0.97; P = .018). However, when considering the median follow up, the differences in breast cancer mortality (RR, 1.01; 95% CI, 0.82-1.24; P = .94) and all-cause mortality (RR, 1.04; 95% CI, 0.86-1.27; P = .68) were not significant. Additionally, the risk ratio for breast cancer mortality for those who received treatment with an aromatase inhibitor vs tamoxifen was 1.25 for years 0 to 4 and 0.80 for years 5 to 9.

When assessing the 10-year recurrence risk by nodal and progesterone status and tumor grade, investigators reported identical proportional reductions in those with node-negative disease (RR, 0.71; 95% CI, 0.57-0.89), and in those with 1 to 3 positive nodes (RR, 0.71; 95% CI, 0.58-0.91). Moreover, the 5-year absolute benefit was more notable for patients with 1 to 3 positive nodes (4.8%) compared with those who were node negative (3.1%), although investigators noted no improvement in 5-year recurrence with aromatase inhibitor treatment in 729 patients with 4 or more positive nodes.


Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Lancet Oncol. Published online February 3, 2022. doi:10.1016/S1470-2045(21)00758-0