The variation and clinical significance of hormone receptors and Her-2 status from primary to metastatic lesions in breast cancer patients

Yan-Yun Zhu, Wen Si, Tie-Feng Ji, Xiao-Qin Guo, Yi Hu, Jun-Lan Yang

The objective of this study is to investigate how the change of hormone receptor (HR) and human epidermal growth factor receptor-2 (Her-2) status is related to patients' clinical features. One hundred ninety-three cases of patients treated at general hospital of PLA from 2000 to 2015 with advanced breast cancer were included. All patients developed recurrence that were re-biopsied and had complete pathological profile both at initial diagnosis and at relapse. HR status before and after relapse were available for all patients, while only 143 cases had Her-2 status at the two stages. The changes of ER, PR, and Her-2 status and their association with clincopathological factors and DFS were analyzed. The discordant rates of ER, PR, and Her-2 status between primary breast cancer and recurrent tumor were 34.2, 38.3, and 16.8 %, respectively. At relapse, the rates of gain of ER and PR positivity were 10.9 and 13.5 %, respectively; the rates of loss of ER and PR positivity were 23.3 and 24.9 %. Loss of positivity was more frequent than gain of positivity (p ER < 0.000, p PR = 0.001). Among patients with Her-2 negative primary tumors, 15.4 % acquired Her-2 positivity at relapse; and among Her-2 positive patients at initial diagnosis, 1.4 % turned to Her-2 negative at relapse; gain of positivity was more frequent than loss of positivity (p < 0.000). Patients with tumor larger than 2 cm in diameter were more likely to experience change of Her-2 status (25.0 vs 5.8 %, p = 0.005). Yet, the change of ER/PR was not significantly associated with the size of primary tumor. Patients with ER positive recurrent disease and PR positive primary tumor had a DFS of more than 40 months. Compared to patients who maintained PR negative, patients who gained PR positivity at relapse had significantly longer DFS by 8.5 % (35.2 vs 26.7 months, p = 0.024). Patients losing ER positivity at relapse had shorter DFS by 7.8 months compared to those with stable ER positive tumors; patients gaining ER positivity experienced longer DFS by 8.3 months; but both differences were not statistically significant. Loss of Her-2 positivity was associated with longer DFS by 13.8 months as opposed to stable Her-2 status, without statistical significance. For patients with Her-2 negative primary tumor, the changes of Her-2 status were not associated with DFS. 34.2, 38.3, and 16.8 % of breast cancer patients had their ER, PR, and Her-2 status changed after recurrence, and these changes of receptor status were associated with DFS to some degree. Gain of PR positivity at relapse was significantly correlated with longer DFS.