The correlation of ESR1 genetic aberrations with estrogen receptor and progesterone receptor status in metastatic and primary estrogen receptor-positive breast carcinomas.

Genetic aberrations in the Estrogen Receptor 1 (ESR1) gene have been identified as an important mechanism of resistance to endocrine therapy in metastatic breast carcinoma. In this study, we aimed to correlate ESR1 genetic aberrations with the ER and PR status in paired metastatic and primary breast carcinomas. Patients with ER-positive breast cancer were divided into two groups: ESR1 genetic aberration (n = 26) and wild-type control (n = 29) based on genetic profiling of their metastatic tumors. Clinicopathological features and ER/PR status were analyzed in paired primary and metastatic tumors. Although there was no significant difference in ER expression between the ESR1 aberration and control groups in primary tumors, ER positivity rate in metastatic tumors was significantly higher in the ESR1 aberration group than in the control group (100% vs. 86%, P < .05). ESR1 aberrated cases were associated with more liver metastases than control tumors (46% vs. 10%, P < .01). The ER percentage and intensity slightly increased from primary to metastatic tumors in the ESR1 aberration group compared to a decrease in both in the wild-type group (percentage increase 2% vs. decrease 19%, P = .0594; intensity increase 0.04 vs. decrease 0.8, p < .05). Patients with ESR1 aberrated metastases were more likely than those with wild-type ESR1 metastases to have the following characteristics: 1) ER percentage ≥90% and intensity >2, as well as PR percentage ≥30% and intensity >1 in metastatic tumors; 2) ER percentage ≥90% and PR percentage ≥70% in primary tumors; and 3) slightly increase in ER percentage and intensity from primary to metastatic tumors. Based on the ER/PR parameters of paired primary and metastatic breast cancer, ESR1 aberration in metastasis may be predicted.