Menopausal status-dependent alterations in the transcript levels of genes encoding ERα, ERβ, PR and HER2 in breast tumors with different receptor status

Abstract

Abstract Breast cancer has distinct causes and prognoses in patients with premenopausal and postmenopausal status. The expression status of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are analyzed by immunohistochemistry to classify molecular subtypes of breast cancer among which huge differences in prognosis exist. In this study, I analyzed the mRNA expression of ESR1 (encoding ERα), ESR2 (encoding ERβ), PGR (encoding PR) and ERBB2 (encoding HER2) based on menopausal status (pre- vs post-menopausal) in breast cancer patients with different receptor status. I found that, in ER-positive or PR-positive or HER2-negative breast tumors, ESR1 transcript levels are higher in tumors from postmenopausal women than those from premenopausal women; in contrast, ESR2 transcript levels are lower in tumors from postmenopausal women than those from premenopausal women. Furthermore, PGR mRNA expression were lower in breast tumors from postmenopausal women than those from premenopausal women, only in those with ER + or PR + status. I also analyzed the expression of these genes between tumors from pre- and post-menopausal patients with breast cancer based on the combination of status of three receptors. Together, the results suggest that mRNA expression of ESR1, ESR2 and PGR might differ depending on menopausal status in breast tumors with certain receptor status. More importantly, the change in the expression of ESR1 and ESR2 following menopause is in the opposite directions in breast cancer patients, pointing to the need to identify molecular mechanisms regulating the expression of ER isoforms post-menopause in breast cancer patients, considering the clinical importance of these receptors on the prognosis of patients.