Galectin-3 as a Candidate Marker of Endocrine-modulator-associated Endometrial Remodeling During Breast Cancer Endocrine Therapy

Breast cancer endocrine therapies may induce endometrial alterations, but the endometrial effects of antiprogestins remain incompletely defined. This study evaluated the effects of tamoxifen, mifepristone, and ulipristal acetate on endometrial morphology and galectin-3 expression, with the aim of exploring galectin-3 as a candidate marker of endocrine-modulator-associated endometrial remodeling.

Endometrial effects were examined in a rat mammary carcinogenesis model treated with tamoxifen, mifepristone, ulipristal acetate, or vehicle control. Uterine tissues were assessed by histology and galectin-3 immunohistochemistry. Complementary in vitro experiments in Ishikawa endometrial adenocarcinoma cells evaluated agent- and dose-associated galectin-3 protein-expression patterns by western blotting. Histological outcomes and in vitro fold-change values were summarized descriptively.

In the analyzed cohort, tamoxifen-treated animals showed the highest descriptive proportion of complex endometrial hyperplasia, whereas mifepristone and ulipristal acetate were associated predominantly with simple hyperplastic changes. Normal endometrial morphology was retained in selected mifepristone- and ulipristal acetate-treated animals and in all control animals. Galectin-3 immunoreactivity was low but detectable in morphologically normal endometrium, whereas hyperplastic lesions showed no detectable galectin-3 immunoreactivity under the staining conditions used. In Ishikawa cells, galectin-3 expression showed agent-specific fold-change patterns: tamoxifen and mifepristone were associated with reduced expression at higher concentrations, while ulipristal acetate showed a non-monotonic pattern with increased expression at low and intermediate concentrations and return toward baseline at the highest concentration.

In this exploratory model, endocrine-modulator-associated hyperplastic endometrial remodeling was accompanied by reduced or undetectable galectin-3 immunoreactivity, while low-level expression was retained in morphologically normal endometrium. These findings support further investigation of galectin-3 as a candidate marker of endocrine-associated endometrial remodeling, but validation in larger animal cohorts and human endometrial samples from treated patients is required.