Abstract

Breast cancer, particularly hormone receptor-positive (HR+) subtypes characterized by estrogen receptor (ER) and/or progesterone receptor (PR) expression, constitutes a significant proportion of cases globally. Targeting hormonal pathways through endocrine therapies has revolutionized treatment strategies, leading to improved outcomes. Current approaches include selective estrogen receptor modulators (SERMs) like tamoxifen, aromatase inhibitors (AIs) such as letrozole, and selective estrogen receptor downregulators (SERDs) like fulvestrant, each tailored to inhibit estrogen signaling and suppress tumor growth. Despite these advancements, challenges such as primary and acquired resistance to therapy persist, driven by complex molecular mechanisms involving altered receptor expression and alternative signaling pathways. Future avenues focus on novel therapeutic targets like ER co-regulators and dual targeting strategies combining endocrine therapies with agents against complementary
pathways. Personalized medicine approaches integrating genomic profiling and liquid biopsies offer promise in optimizing treatment selection and monitoring response. The integration of immunotherapy represents a frontier in enhancing anti-tumor immunity within HR+ breast cancer contexts. This review synthesizes current knowledge and explores future directions to navigate hormonal pathways effectively, aiming to further advance personalized treatment strategies and improve patient outcomes.