Abstract PO2-15-01: EZH2 protein expression in early hormone receptor positive HER2 negative breast cancer with high recurrence score
Authors: Lin Shuwen , Lo Yungtai , Makower Della , Lu Jinyu , Fineberg Susan 
Published: May 2024

Background: The 21 gene recurrence score assay (RS) is both prognostic and predictive of chemotherapy benefit in hormone receptor positive (HR+) HER2 negative (HER2-) breast cancer (BC). While patients (pts) with RS&gt;26 benefit from chemoendocrine therapy, they remain with poorer outcomes than pts with lower RS. Overexpression of the enhancer of zeste homolog 2 oncoprotein (EZH2) is linked to poor prognosis in multiple cancers, and is associated with resistance to endocrine therapy in HR+/HER2- BC. We evaluated association between EZH2 expression and distant metastases in a single institution cohort of pts with HR+/HER2- BC and RS&gt;26. Methods: Pts with ER+/HER2- BC and RS&gt;26 who underwent surgery at our institution between 2011 and 2017 were identified from pathology database. All pts with available tumor specimens were included in analysis. Immunohistochemistry was performed to evaluate EZH2 protein expression within invasive tumor cells and quantified as follows: nuclear staining intensity was scored as 3 (strong), 2 (moderate), 1 (weak), and 0 (no stain). Percentage of positive nuclei at each intensity was multiplied, and all values were added to arrive at a final EZH2 score multiplied by 100, ranging from 0 (no nuclei staining) to 300 (strong nuclear staining in 100% of cells). The investigator scoring EZH2 staining was blinded as to pts clinical outcomes. EZH2 score was both evaluated as a continuous variable and dichotomized at a score of 140. Associations between EZH2 score and age at diagnosis, progesterone receptor (PR) status, tumor size, grade, node involvement, RS, and metastatic recurrence were determined by Kruskal-Wallis or Wilcoxon rank-sum tests for categorical variables and Spearman correlation coefficients for continuous variables. Results: 45 pts were included. Median (IQR) age was 60 (55, 69). 32 (71.1%) pts received chemotherapy. 37 (82.2%) pts received endocrine therapy. Tumor size was ≤2 cm in 26 pts (57.8%), and &gt;2 cm but ≤5 cm in 19 pts (42.2%). 7 pts (15.6%) had involved axillary nodes. Median RS was 31 (28, 37). Median EZH2 score was 120 (90, 170). With median follow-up of 7.6 (5.7, 9.2) years, 4 pts (8.9%) developed distant metastatic disease. EZH2 score was significantly associated with development of metastatic disease, both when EZH2 was expressed as a continuous variable (p=0.040) and when dichotomized at 140 (p=0.015). EZH2 score was positively associated with RS (r = 0.37; p=0.013) and negatively associated with age at diagnosis (r = -0.44; p=0.002), but was not associated with clinicopathologic features such as tumor size, grade, node involvement, and PR status. Younger age was also associated with development of metastatic disease (p=0.023), whereas tumor size, grade, node involvement, PR status, RS, and receipt of chemotherapy were not. Conclusion: In this single institution cohort of pts with early HR+/HER2- BC and high RS, EZH2 protein expression and younger age were associated with development of distant metastases. This preliminary data suggests that determination of EZH2 expression levels may assist in risk stratification of pts with high RS. This should be investigated in a larger data set.

Citation Format: Shuwen Lin, Yungtai Lo, Della Makower, Jinyu Lu, Susan Fineberg. EZH2 protein expression in early hormone receptor positive HER2 negative breast cancer with high recurrence score [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-15-01.