Aromatase inhibitors outperform tamoxifen in premenopausal women

In premenopausal women with early-stage breast cancer, adjuvant ovarian suppression can be combined with tamoxifen or an aromatase inhibitor. A meta-analysis of 4 randomised controlled trials showed that aromatase inhibition outperforms tamoxifen.

For women with early-stage, hormone receptor (HR)-positive breast cancer, adjuvant treatment with tamoxifen reduces their 15-year risk of breast cancer recurrence and death by about a third [1]. Aromatase inhibitors are even more effective than tamoxifen in postmenopausal women but, used alone, are ineffective in premenopausal women due to compensatory ovarian oestrogen production [2]. A meta-analysis was performed on individual patient data from 4 randomised-controlled trials, including 7,030 premenopausal women with oestrogen receptor (ER)-positive breast cancer: ABCGS12 (NCT00295646), TEXT (NCT00066703), SOFT (NCT00066690), and HOBOE (NCT00412022). All women received ovarian suppression or ablation and were randomised 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. Ms Rosie Bradley (University of Oxford, UK) presented the results [3].

The average annual rate of recurrence was 21% lower (RR 0.79; 95% CI 0.69–0.90; P=0.0005) for women allocated to an aromatase inhibitor compared with tamoxifen with an absolute 10-year gain in recurrence of 2.8% (14.7% vs 17.5%; see Figure). The absolute 10-year gain in distant recurrence was 1.9% (10.2% vs 12.1%). In addition, no significant absolute gain in breast cancer mortality was observed (6.8% vs 7.2%). The greatest benefit from aromatase inhibition was seen in years 0–4 (RR 0.68; 99% CI 0.58–0.80) during the period when treatments differed, with no further benefit or loss of benefit in years 5–9 (RR 0.98; 99% CI 0.73–1.32). Limited follow-up data was available beyond year 10. In contrast to the findings of the meta-analysis of aromatase inhibition versus tamoxifen in postmenopausal women, aromatase inhibition appeared ineffective in N4⁺ disease.

Figure: Recurrence of breast cancer after aromatase inhibition or tamoxifen treatment [3].



 

 

 

 

 

Based on these results, Ms 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.”

1. Early Breast Cancer Trialists' Collaborative Group. Lancet 2011;378:771–784.
2. Early Breast Cancer Trialists' Collaborative Group. Lancet 2015;386:1341–1352.
3. 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. GS2-04, SABCS 2021 Virtual Meeting, 7–10 December.

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Posted on 31 January, 2022