Biomarker changes and its prognostic significance after chemotherapy in patients with de novo metastatic breast cancer: A retrospective cohort study.

Abstract

e13160 Background: It is unclear whether the expression of biomarkers such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki-67 proliferation index changes after chemotherapy (CT) in patients with de novo metastatic breast cancer (dnMBC). The study aimed to investigate the expression of the biomarkers before and after CT and its impact on the prognosis of dnMBC patients.The study was approved by the Ethics Committee of Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine (2017-AF29-058). Methods: Using hospital-based database, we conducted a retrospective cohort study on dnMBC patients who received CT between February 2010 and December 2017. Based on clinicopathological data (including biopsy at the initial diagnostic stage and re-biopsy after chemotherapy), changes in pathological findings (ER, PR, HER-2, Ki-67) following CT were examined. The effect of biomarker conversion on prognosis was evaluated. The primary outcome was overall survival (OS). Kaplan-Meier method and log-rank test was used for survival analyses. Univariable and multivariable analyses were performed using the Cox proportional hazard model to identify statistically significant prognostic factors. Analyses were conducted using Stata software (version 18.0, STATA Corp., College Station, Texas, USA). Results: The study included 192 female patients. The change rates of ER, PR, HER-2 and Ki-67 before and after CT were 9.9%, 17.2%, 6.2% and 25.5% respectively. Among them, the change in negative-to-positive expression of Ki-67 was the most common type of discordance observed. There was no statistical difference in OS between patients with changes in the four biomarkers and patients with no changes in the biomarkers (all p>0.05). Interestingly, positive conversion of ER and PR, as well as persistent positive HER2 and Ki-67, were significantly associated with poor prognosis (p<0.001, p<0.001; p=0.029, p<0.001). Family history, initial metastatic site, and tumor grade were independent variables related to survival (p=0.002, p<0.001, p<0.001). Conclusions: Changes in ER, PR, HER2, and Ki-67 status were observed in patients after CT. Positive conversion of ER and PR, and persistent positive expression of HER2 and Ki-67 may indicate a poor prognosis. Further research is needed to determine whether biomarker expression investigations are needed following CT to optimize treatment options and improve survival.