Changes in expression of breast cancer tumor biomarkers between primary tumors and corresponding metastatic sites: common patterns and relationships with survival

In metastatic breast cancer, differences in expression patterns of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) between the primary tumor (PT) and metastatic site (MET) have been reported. However, there is limited understanding of the relationship of tumor subtype discordance and overall survival (OS). We evaluated patterns of ER/PR/HER2 in PTs and corresponding METs and assessed the relationship between these patterns and OS.

Patients diagnosed at our center with metastatic breast cancer (2011–2020) were included. ER/PR were stratified as < 1%/1–10%/ > 10% by immunohistochemistry and HER2 as positive/negative by immunohistochemistry/FISH. Tumor subtypes were classified as ER or PR + /HER2−, HER2+ , or triple-negative. Biomarker discordance data from PTs to METs were analyzed for expression patterns. OS was assessed.

Of 254 patients, 41 (16.1%) had synchronous and 213 (83.9%) had metachronous METs. Category change of ER/PR/HER2 expression was observed in 56 (22.0%), 117 (40.5%), and 30 (11.8%) patients, respectively. Tumor subtype changed in 56 (22.0%) patients. We identified a difference between PT and MET from ER > 10% to ER < 1% (n = 28,16.2% p < 0.01); PR > 10% to PR < 1% (n = 54,48.2%, p < 0.001); PR > 10% to PR 1–10% (n = 18,16.1%, p < 0.001), and ER or PR+/HER2− to triple-negative (n = 19,13.0%, p = 0.03). In log-rank analysis, change from an ER or PR+/HER2− (5-year OS 88.6%) PT to a HER2+(67.5%) or triple-negative (54.6%) MET was associated with decreased survival (p < 0.01); however, in multivariate analysis, discordant biomarker expression was not associated with decreased survival (p > 0.05).

Tumor expression of ER/PR/HER2 can differ between the PT and MET. Loss of ER/PR expression is common and may be related to worse survival. Routine assessment of MET tumor markers could inform prognosis and therapeutic decision-making.