Ovarian suppression + aromatase inhibitor prevents recurrence in premenopausal breast cancer over long term

The benefits in terms of prolonged disease-free survival (DFS) and reduced risk of recurrence with ovarian function suppression (OFS) persisted over 12–13 years in premenopausal women with hormone receptor-positive (HR+) breast cancer, according to new data from the TEXT and SOFT randomized trials presented at SABCS 2021.

In particular, combining an aromatase inhibitor (AI) with OFS continued to lead to significantly higher DFS rate than the combination with tamoxifen.

The 12-year DFS rates were 80.5 percent in the AI + OFS arm compared with 75.9 percent in the tamoxifen + OFS arm — corresponding to a 4.6 percent absolute improvement with the AI combination (hazard ratio [HR], 0.79, 95 percent confidence interval [CI], 0.70–0.90). [SABCS 2021, abstract GS2-05]   

Similarly, improvements in distant recurrence-free interval (DRFI) and invasive breast cancer-free interval (BCFI) continued to be significant with AI + OFS, by 4.1 percent and 1.8 percent, respectively, over tamoxifen + OFS at 12 years.   

These results were from an updated analysis of two randomized studies with similar design, TEXT and SOFT. Participants were 5,707 premenopausal women with early HR+ breast cancer (2,660 in TEXT and 3,047 in SOFT). In the SOFT trial, patients were randomized to receive adjuvant tamoxifen alone or to OFS plus either tamoxifen or the AI exemestane; while the single-agent tamoxifen arm was omitted in TEXT.  

Among the 4,690 patients who received OFS (either in combination with tamoxifen or AI), 953 achieved DFS and 473 had died.

At 12 years, overall survival (OS) rate remained high in both groups, at 90.1 percent in the AI + OFS arm and 89.1 percent in the tamoxifen + OFS arm (HR, 0.93; 95 percent CI, 0.78–1.11).

When restricting the analysis to women with HER2-negative tumours who had received chemotherapy, there appeared to be OS benefit t 12 years in favour of AI + OFS over tamoxifen + OFS (84.4 percent vs 81.1 percent for SOFT; 86.8 percent vs 83.5 percent for TEXT).

Other clinical outcomes were also better with the AI than the tamoxifen combination in HER2-negative patients with high-risk features. For instance, 12-year DFS was improved by 7.4 percent and OS by 2.7 percent in patients with pN1a disease; and by 10.6 percent and 4.5 percent, respectively, in women whose tumours measured >2cm, all in favour of the AI + OFS combination.

“Adjuvant exemestane + OFS, as compared with tamoxifen + OFS, shows a sustained reduction in the risk of recurrence, more consistent in HER2-negative patients and in those with high-risk disease features, for example, indication for adjuvant chemotherapy and G3 tumours,” said the researchers.

“Oncologists may use this information to discuss [the] potential benefits of exemestane + OFS with individual patients,” they suggested, adding that they planned to follow up the patients for another 5 years.