Jay Gupta, Sourabh D Jain, Arun K Gupta
Breast cancer remains one of the most prevalent malignancies worldwide and a leading cause of cancer-related mortality, particularly in low- and middle-income countries undergoing rapid lifestyle transitions. Among its subtypes, oestrogen receptor-positive (ER-positive) breast cancer accounts for approximately 70–75% of cases and is strongly influenced by hormonal regulation. Oestrogen plays a critical role in tumor initiation and progression through both genomic and non-genomic mechanisms, primarily mediated by oestrogen receptor alpha (ERα), which regulates genes involved in cell proliferation, survival, and differentiation. Additionally, signalling pathways such as PI3K/AKT and MAPK further enhance tumour growth and metastasis. In contrast, oestrogen receptor beta (ERβ) often exhibits anti-proliferative effects, and the balance between ERα and ERβ expression is crucial in determining disease progression and therapeutic response. Tamoxifen, a selective oestrogen receptor modulator (SERM), has been a cornerstone in the treatment and prevention of ER-positive breast cancer for several decades due to its ability to block oestrogen signalling. Despite its clinical success, long-term use is associated with significant limitations, including drug resistance and adverse effects such as endometrial abnormalities. These challenges are linked to alterations in oestrogen receptor signalling pathways and tumour microenvironment dynamics. Current research focuses on overcoming tamoxifen resistance and improving therapeutic outcomes through the development of novel derivatives and targeted approaches. Understanding the molecular mechanisms of oestrogen action and receptor modulation is essential for advancing effective treatment strategies and improving patient prognosis in hormone-dependent breast cancer.
