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

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 (IHC) to classify molecular subtypes of breast cancer among which large differences in prognosis exist.

The mRNA expression of ESR1 (encoding ERα), ESR2 (encoding ERβ), PGR (encoding PR), and ERBB2 (encoding HER2) was analyzed based on menopausal status (pre- vs post-menopausal) in tumors from breast cancer patients with different receptor status, in R programming environment, using transcriptomics data from TCGA-BRCA project.

In ER−positive or PR-positive or HER2−negative breast tumors, ESR1 transcript levels were found to be higher in tumors from postmenopausal women than those from premenopausal women; in contrast, ESR2 transcript levels were lower in tumors from postmenopausal women than those from premenopausal women. Furthermore, PGR mRNA expression was lower in breast tumors from postmenopausal women than those from premenopausal women, only in those with ER + or PR + status. The expression of these genes between tumors from pre- and post-menopausal patients with breast cancer was also analyzed 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 showing the need to identify particular molecular mechanisms regulating the expression of ER isoforms post-menopause in different directions in breast cancer patients, considering the high clinical importance of these receptors in terms of the prognosis of patients with breast cancer.