Stability of estrogen receptor status in breast carcinoma

Abstract

BACKGROUND:The purposes of this study were to address a persistent controversy as to whether the ER status of a primary tumor remains stable during progression to metastasis and to evaluate the influence of disease course and prior systemic therapy on ER status. METHODS: Breast carcinomas from 227 women with known ER status in both primary tumor and paired metastasis were retrospectively reviewed. ER status was compared between primary and metastatic tumors with respect to metastatic site, interval between two ER assays, and intervening chemotherapy and endocrine therapy. Semiquantitative comparison of ER values was performed for 92 tumor pairs. RESULTS: ER status agreed in 210 (92.5%) patients, including 147 positive and 63 negative. Of the 17 patients (7.5%) with discordant ER status, both negative to positive conversion (n ¼ 7) and positive to negative conversion (n ¼ 10) were observed. ER discordance was not significantly associated with metastatic site (locoregional vs distant), time interval between assays (<5 years vs. 5 years), or intervening chemotherapy and endocrine therapy. Semiquantitative levels of ER expression were similar between primary and metastatic tumors. In discordant cases, variations in testing methods and marginal scores were common. CONCLUSIONS: ER status in breast carcinoma is generally stable during progression to metastasis. Preanalytical and analytical variability may contribute to discordance in some cases. Given the importance of ER status for clinical management, ER testing in metastatic breast carcinoma should be repeated, especially for patients whose clinical courses are not compatible with stated ER status. Cancer 2011;117:705-13.

Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain

“…A switch of ERα and PR (29% each) was within the wide range of conversions reported earlier for other sites of relapse [8-11,26,27]. …”

Expression of antigen processing and presenting molecules in brain metastasis of breast cancer

“…As negative ER and PR status has been determined to be a strong predictor of poor prognosis [49–51], these results suggested that TAP2 and ER/PR status might be two independent indicators of breast cancer prognosis and function in independent mechanisms. Recent studies have shown some degrees of discordance in ER and PR status between primary and metastatic lesions [52,53]. In fact, in brain metastases, there were no associations between the TAP2 expression levels and ER/PR status, likely supporting our notion that these are two independent factors.…”

Histone methyltransferases regulate the transcriptional expression of ERα and the proliferation of tamoxifen-resistant breast cancer cells

“…Almost half of patients with advanced disease do not respond to the drug and almost all patients with metastatic disease eventually develop resistance to it [3,4]. Intriguingly, the majority of patients who have relapsed on tamoxifen treatment retain ERα expression [5,6]. Several preclinical studies targeting ERα in tamoxifen-resistant cancers have yielded promising results [7][8][9].…”