In pre-menopausal women with early-stage, ER-positive breast cancer, adjuvant ovarian suppression can be combined with tamoxifen or an aromatase inhibitor. A meta-analysis of 4 randomized controlled trials, including 7,030 participants, shows that aromatase inhibitors outperform tamoxifen. However, aromatase inhibition led to more bone fractures.
For women with early-stage, HR-positive breast cancer, adjuvant treatment with tamoxifen reduces their 15-year risk of death from breast cancer by about a third [1]. Aromatase inhibitors are even more effective than tamoxifen in postmenopausal women but, used alone, are ineffective in pre-menopausal women due to compensatory ovarian estrogen production [2]. Several trials have assessed whether, if administered with ovarian suppression, aromatase inhibitors may also be more effective than tamoxifen at preventing breast cancer recurrence in premenopausal women, but trial results have been inconsistent. Therefore, a meta-analysis was performed on individual patient data from 4 randomized controlled trials, including 7,030 pre-menopausal women with ER-positive breast cancer: ABCGS12 (NCT00295646), TEXT (NCT00066703), SOFT (NCT00066690), and HOBOE (NCT00412022). In these trials, all women received ovarian suppression or ablation and were randomized to receive either an aromatase inhibitor or tamoxifen for 3 years (in ABCSG12) or 5 years (in SOFT, TEXT, and HOBOE). Median follow-up was 8.0 years. Primary outcomes for the meta-analysis were time to invasive breast cancer recurrence (distant, loco-regional, or new contralateral breast primary) and breast cancer mortality. Dr. Rosie Bradley (University of Oxford, UK) presented the results [3]. Overall, the annual rate of recurrence averaged 21% lower (RR 0.79; P=0.0005) for women allocated to aromatase inhibitor compared with tamoxifen with an absolute 10-year gain in recurrence of 2.8% (14.7% vs 17.5%). The absolute 10-year gain in distant recurrence was 1.9% (10.2% vs 12.1%). In addition, there was no significant absolute gain in breast cancer mortality (6.8% vs 7.2%). The main benefit from aromatase inhibition was seen in years 0-4 (RR 0.68), during the period when treatments differed, with no further benefit or loss of benefit in years 5-9 (RR 0.98). Currently, limited follow-up data is available beyond year 10. The proportional reduction in recurrence did not vary by age, BMI, or by tumor size, tumor grade, histological subtype, or presence/absence of chemotherapy. In contrast to the findings of the meta-analysis of aromatase inhibitors versus tamoxifen in postmenopausal women, aromatase inhibition appeared ineffective in N4+ disease. There were more bone fractures in women receiving aromatase inhibitor compared with tamoxifen (5.0% vs 3.8%; P=0.02). Among these younger women, few non-breast cancer deaths occurred (0.9% with aromatase inhibitor vs 0.7% with tamoxifen) and the incidence of endometrial cancer was low (0.2% with aromatase inhibitor vs 0.3% with tamoxifen). Based on these results, Dr. Bradley concluded that “Using an aromatase inhibitor rather than tamoxifen, in premenopausal women receiving ovarian suppression, reduces the risk of breast cancer recurrence by about 20% compared with tamoxifen. Aromatase inhibition comes with more bone fractures, but no increase in non-breast cancer mortality.”
- Early Breast Cancer Trialists’ Collaborative Group. Lancet 2011;378:771-784.
- Early Breast Cancer Trialists’ Collaborative Group. Lancet. 2015;386:1341-1352.
- Bradly R, et al. Aromatase inhibitors versus tamoxifen in pre-menopausal women with estrogen receptor positive early stage breast cancer treated with ovarian suppression: A patient level meta-analysis of 7,030 women in four randomised trials. SABCS 2021 Virtual Meeting, abstract GS2-04.
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