Role of Estrogen Receptor B as a Potential Biomarker in Triple - Negative Breast Cancer

Abstract

riple-Negative Breast Cancer (TNBC), is a specific subtype of breast cancer which is highly aggressive, has high metastatic potential, prone to relapse and poor prognosis. TNBC lacks the expression of Estrogen receptor (ER), Progesterone receptor (PR) and Human Epidermal Growth Factor receptor. (HER-2) thus they are not sensitive to hormonal therapy for HER-2 specific treatment. TNBC accounts for 10-20% of total breast cancer incidence worldwide. The discovery of Estrogen receptor β (ER β) in the nineteenth century opened new perspectives in the field of diagnosis and treatment for different types of cancer.ER β is located on chromosome 14q23.2, which was proposed to be anti-proliferative in tumour progression. In the history, from the past 26 years, an increase in the body of evidence supports that ER β has a vital role in TNBC. Approximately 80% of normal breast epithelial cells express ERβ. ERα is involved in tumorigenesis and progression of breast cancer, its role being already elucidated and proven that ER is considered a clinical biomarker for Breast Cancer. Anti-hormonal therapy is commonly used in breast cancer patients with ERα expression, including SERM like Tamoxifen, as it is the most effective and widely used anti estrogen therapy for breast cancer. However, only 70% of ERα positive breast cancers respond to tamoxifen treatment and 30% of patients receiving the therapy relapse and become resistant to this therapy. Tamoxifen is a type of hormonal therapy known as selective estrogen receptor modulator (SERM) and given to ER-positive tumours. In this study, the systematic evaluation of the expression of functional ERβ is carried out in a synergistic manner with the anti-tumour action of tamoxifen. In recent years the mTOR pathway which transmits signals from the cell membrane into the nucleus and activates multiple oncogenic programs has been found to play a crucial role in the regulation of breast cancer cell growth. It has been found that mTOR signaling modulates Estrogen receptor function. From the data, presently available it can be deduced that ER β has the potential to be established as a prognostic biomarker for TNBC. This can be achieved by analyzing the expression level of ERβ during the anti-estrogen treatment (Tamoxifen) at transcript and protein levels by RT PCR and Western blotting, respectively. The study aims to attain an understanding of Tamoxifen and its effectiveness that directly aids in a better prognosis for TNBC.