CLINICAL SIGNIFICANCE OF ESTROGEN RECEPTOR 1 GENE PROMOTOR METHYLATION IN HORMONAL THERAPY RESISTANT BREAST CANCER PATIENTS

Abstract

Breast cancer (BC) remains the most common malignancy in women worldwide, and is the leading cause of female cancer-related mortality. This warrants early diagnosis and the improvement of specific subtype treatments, thus leading to significant improvements of the 5-year survival rates. However metastatic breast cancer (MBC) still remains incurable. About 70% of breast cancer patients express estrogen receptor alpha (ERα) and are considered estrogen dependent. Thus these hormone receptor positive patients are candidates for endocrinal therapy. Unfortunately, the efficacy of endocrine therapy is limited by the development of BC endocrine resistance which is considered a major challenge in both the adjuvant and metastatic settings, and nearly half of ER+ve BC patients treated with hormonal therapy become unresponsive to treatment over time. This warrants the need for investigating markers that reflect hormonal resistance mechanisms, such as epigenetic alterations including aberrant DNA methylation and chromatin remodeling. An epigenetic marker like the ESR1 promoter methylation might eventually be a one promising tool that help clinicians make the right decisions, since ESR1 gene promotor methylation might potentially affect the response to endocrine treatment.