Biomarker discordance after neoadjuvant systemic therapy and associated patterns of recurrence.

Abstract

3149 Background: Understanding and addressing intratumor heterogeneity in breast cancer (BC) is crucial for advancing research and improving patient outcomes. The identification of biomarkers for targeted therapies is complex when dealing with heterogeneous tumors, and this heterogeneity complicates cancer outcomes since it affects treatment response, and the development of resistance. Methods: A single institution retrospective review of patients with BC who received neoadjuvant systemic therapy (NAST) followed by definitive surgical resection from 2008 to 2022 was performed. Initial tumor biopsies were tested for hormone receptors (HR) [estrogen receptor (ER) and progesterone receptor (PR)], and HER2 status and repeated on the residual tumor tissue after NAST. HER2 status was categorized into HER2-negative, HER2-low, and HER2-positive and HR status was categorized into ER and/or PR positive or negative based on the 2023 ASCO-CAP guidelines. HER2 and HR concordance and discordance rates were obtained and patients who had disease recurrence were identified and analyzed using descriptive statistics and Fisher’s exact test. Results: 480 patients with BC received NAST, and 143 patients with residual disease had pre and post treatment biomarker data available for analysis with a median post-surgery follow up of 15.2 months. Discordance in either HER2 or HR status was identified in 50% (72/143) of samples. Out of 143 patients, 44 patients had disease recurrence in which 50% (22/44) of tumors exhibited biomarker discordance. Among the changes in biomarker status, a shift in PR expression occurred most frequently in 27% of tumors (12/44). A change from HER2-low to HER2-negative status, as well as changes in ER expression occurred in 11% of tumors (5/44). 14% (6/44) of tumors had changes in both HER2 and HR. In patients who did not have recurrence, 51% (50/99) of tumors exhibited biomarker discordance. A HER2-low to HER2-negative status occurred most frequently in 18% (18/99). A change in ER expression occurred second most frequently, in 14% (14/99) of tumors. There was no statistical significance of discordance rates in the recurrence group and non-recurrence group (p-value=0.96). Conclusions: Tumor heterogeneity plays a role in shaping the distinct tumor biology of each patient. While the rates of biomarker discordance were comparable between samples with and without recurrence, the importance of HR discordance in this group requires extensive long-term monitoring. Our research highlights the importance of biomarker changes in a curative setting. Considering the implications for treatment, further investigation into additional biological and tumor-related factors associated with recurrence is warranted. [Table: see text]