Introducere. Estrogenii au un rol fundamental în patogene-za cancerului mamar hormonodependent, prin mecanisme variate de activare a receptorilor estrogenici. Dintre acestea, activarea independentă de ligand se remarcă prin impactul său asupra progresiei tumorale şi asupra sensibilităţii la terapiile endocrine. Scop. Evidenţierea importanţei mecanismului de activare independent de ligand al receptorului estrogenic în înţelegerea variabilităţii răspunsului terapeutic în cancerele mamare ER pozitive. Material şi metode. Au fost selectate şi analizate publicaţii din ultimii 5 ani, din reviste de specialitate indexate în baza de date PubMed, folosind următoarele
Introduction. Estrogens play a fundamental role in the pathogenesis of hormone-dependent breast cancer through multiple complex mechanisms involving estrogen receptor activation. Among these, ligand-independent activation stands out due to its impact on tumor progression and sensitivity to endocrine therapies. Objective. Highlighting the importance of the estrogen receptor ligand-independent activation mechanism in understanding the variability of therapeutic responses in ER-positive breast cancers. Material and methods. Publications from the last 5 years were carefully selected and analyzed, from specialized journals indexed in the PubMed database, using the following keywords: breast cancer, estrogen, estrogen receptor, ligand-independent activation, hormone therapy and tumor resistance, to highlight the clinical and molecular implications. Results. Recent studies have shown that, in ER-positive breast cancer, the ligand-independent mechanism enables activation of the estrogen receptor alpha even in the absence of estrogen, through successive phosphorylation mediated by epidermal growth factor receptors (EGFR, HER2), as well as through the appearance of mutations in the ESR1 coding gene. These changes activate the PI3K/Akt and MAPK signaling cascades, promoting cell proliferation and causing resistance to classical endocrine therapies, including selective estrogen receptor modulators (e.g. tamoxifen), which act strictly by blocking the interaction with the ligand. Conclusion. Knowledge of the ligand-independent activation mechanism in ER-positive breast cancers explains the lack of response to classical endocrine therapies and supports the development of modern pharmacological strategies, capable of completely abolishing estrogen receptor function.
