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Aromatase Inhibitors vs. Tamoxifen in Premenopausal Women With Breast Cancer

By: Lauren Harrison, MS
Posted: Friday, March 25, 2022

The use of an aromatase inhibitor in combination with ovarian suppression appears to reduce the risk of breast cancer recurrence in premenopausal women with estrogen receptor–positive disease when compared with tamoxifen. A meta-analysis of individual patient data was published by the Early Breast Cancer Trialists’ Collaborative Group in The Lancet Oncology.

Researchers identified four clinical trials where aromatase inhibitors such as anastrozole, exemestane, or letrozole were compared with tamoxifen for 3 or 5 years in premenopausal women with estrogen receptor–positive breast cancer. In addition to the aromatase inhibitors or tamoxifen, patients also received ovarian suppression or ablation. These trials studied a combined 7,030 women between June 1999 and August 2015.

The rate of breast cancer recurrence was lower for women who received an aromatase inhibitor compared with those who received tamoxifen (first event rate ratio [RR] = 0.79, P = .0005) after a median follow-up of 8 years. Overall, the probability of recurrence after aromatase inhibitor therapy was 6.9%, and it was 10.1% with tamoxifen therapy. The main benefit of aromatase inhibitors was seen in the first 4 years of therapy (RR = 0.68), with a 3.2% absolute risk reduction in 5-year recurrence risk. In years 5 to 9 and beyond year 10, no further benefit or loss of benefit was observed (RR = 0.98, P = .89). Distant recurrences were reduced among patients receiving aromatase inhibitors as well (RR = 0.83, P = .018). There was no difference in the two groups in terms of breast cancer mortality, death without recurrence, or all-cause mortality.

In regard to safety, patients treated with aromatase inhibitors had more bone fractures than the tamoxifen group (6.4% vs. 5.1%, RR = 1.27, P = .017). Deaths due to something other than breast cancer were rare (< 1%) in both groups. Fewer than 0.5% of patients in each group developed endometrial cancer.

Disclosure: For a full list of authors’ disclosures, visit thelancet.com.


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