Early breast cancer: AIs reduce recurrence vs tamoxifen in premenopausal women on ovarian suppression

Aromatase inhibitors (AIs) reduce the risk of recurrence in premenopausal women with oestrogen receptor (ER)–positive early-stage breast cancer receiving ovarian suppression, a meta-analysis of four randomized trials has shown.

Researchers analyzed data from 7,030 premenopausal women with ER-positive operable breast cancer enrolled in four identical trials (ABCSG XII, SOFT, TEXT, and HOBOE trials) that compared treatment with AIs (ie, anastrozole, exemestane, or letrozole) vs tamoxifen for 3 years or 5 years. The women, enrolled between 17 June 1999 and 4 August 2015, received ovarian suppression (ie, goserelin or triptorelin) or ablation along with randomized treatment and were followed up for a median of 8 years. Primary outcomes were breast cancer recurrence (distant, locoregional, or contralateral), breast cancer mortality, death without recurrence, and all-cause mortality. [Lancet Oncol 2022;doi:10.1016/S1470-2045(21)00758-0]

Results showed a significant reduction in the rate of any breast cancer recurrence in women randomized to receive an AI vs tamoxifen. At 5 years and 10 years, recurrence rates were 6.9 percent vs 10.1 percent and 14.7 percent vs 17.5 percent (rate ratio [RR], 0.79; 95 percent confidence interval [CI], 0.69 to 0.90; p=0.0005), respectively.

“The main benefit from AIs on any recurrence was seen in years 0–4 of follow-up [RR, 0.68; 99 percent CI, 0.55 to 0.85; p<0.0001], the period when treatments differed, with no further benefit, or loss of benefit, in years 5–9 [RR, 0.98; 99 percent CI, 0.73 to 1.33; p=0.89], or beyond year 10,” the researchers pointed out.

Distant recurrence was also significantly reduced with AIs vs tamoxifen, with 10-year rates of 10.2 percent vs 12.1 percent (RR, 0.83; 95 percent CI, 0.71 to 0.97; p=0.018).

“However, with a median follow-up of 8 years, there was no significant difference [between AIs and tamoxifen] in breast cancer mortality [RR, 1.01; 95 percent CI, 0.82 to 1.24; p=0.94], or all-cause mortality [RR, 1.04; 95 percent CI, 0.86 to 1.27; p=0.68],” the researchers noted. “The RR for breast cancer mortality after treatment with an AI vs tamoxifen was 1.25 [99 percent CI, 0.85 to 1.85] in years 0–4 of follow-up and 0.80 [99 percent CI, 0.54 to 1.19] in years 5–9.”

Death without recurrence also did not differ significantly between AIs and tamoxifen (RR, 1.30; 95 percent CI, 0.75 to 2.25; p=0.34).

“Longer follow-up is needed to assess any impact on breast cancer mortality,” the researchers noted.

“Toxicity from AIs and tamoxifen in premenopausal women, as reported from the individual trial publications, was similar to that seen in postmenopausal women,” they wrote.

Bone fractures occurred more frequently in women treated with AIs vs tamoxifen (6.4 percent vs 5.1 percent; RR, 1.27; 95 percent CI, 1.04 to 1.54; p=0.017).

Non–breast cancer deaths (0.9 percent vs 0.7 percent; RR, 1.30; 95 percent CI, 0.75 to 2.25; p=0.36) and endometrial cancer (0.2 percent vs 0.3 percent; RR, 0.52; 95 percent CI, 0.22 to 1.23; p=0.14) were rare and did not differ significantly between AIs and tamoxifen.

“Results from this meta-analysis suggest that using an AI rather than tamoxifen in addition to ovarian function suppression for premenopausal women reduces the absolute risk of recurrence by 3 percent at 5 years and 10 years,” the researchers concluded. “Reassuringly, we found no increase in non–breast cancer deaths over the 10-year follow-up period.”