Breast density reduction as a predictor for prognosis in premenopausal women with hormone receptor–positive breast cancer: A retrospective analysis of the ASTRRA study.

Abstract

531 Background: While the relationship between mammographic breast density (MD) decline and anti-hormone therapy efficacy has been reported in estrogen-receptor (ER)-positive breast cancer, it is still unclear in premenopausal women and in the case of adding ovarian function suppression (OFS) to anti-hormone therapy. We aimed to investigate the MD reduction (MDR) rate and impact of MDR on prognosis stratified by treatment from the updated result of the ASTRRA trial. Methods: ASTRRA trial, a randomized phase 3 study, showed that adding ovarian function suppression (OFS) to tamoxifen (TAM) improved survival in premenopausal women with ER+ breast cancer after chemotherapy. We updated survival outcomes with a median follow-up of 108 months. We assessed mammography taken before treatment and the follow-up mammography taken annually for up to five years after initiation of treatment. MD was classified into four categories based on the Breast Imaging Reporting and Data System. MDR positivity was defined as a downgrade in MD among follow-up mammography up to two years after randomization, with the pretreatment MD grade as a reference. Results: Among the 1,293 patients from ASTRRA trial, we successfully evaluated MDR in 947 patients, of which 796 (83.4%) belong to high MD (grade C or D). The patient characteristics were similar between the entire ASTRRA trial and the subgroup with available MDR. There was no difference in MDR-positive rate between two treatment groups (106 of 477 [22.2%] in TAM-only group vs. 87 of 470 [18.5%] in TAM + OFS group, P =.156). MDR-positivity was significantly associated with better disease-free survival (DFS) in TAM + OFS group (estimated 8-year DFS: 92.9% in MDR-positive vs. 82.2% in MDR-negative, P =.013), but did not in TAM-only group (estimated 8-year DFS: 80.3% in MDR-positive vs. 80.2% in MDR-negative, P =.927; Pinteraction =.025). Simialr trends were observed in terms of recurrence-free survival, distant metastasis-free survival (DMFS), locoregional-free survival, and overall survival. In addition, MDR-positivity was an independent factor for favorable DFS (adjusted hazard ratio [HR], 0.37; 95% CI, 0.16 to 0.86; P =.021) and DMFS (adjusted HR, 0.35; 95% CI, 0.13 to 0.98; P =.045) in TAM + OFS group. Conclusions: Although the proportion of patients with MDR-positive was comparable between the two treatment groups, MDR-positive was independently associated with favorable outcomes only in TAM + OFS group. Future work is warranted to verify the mechanism by which the association between MDR and clinical benefit differs according to the treatment group. Clinical trial information: NCT00912548.