Abstract

Abstract Background: Breast cancer patients with HER2-2+ expression had heterogeneous characteristic. Treatment decision is of great importance after progression. Objective: We explored patients with HER2-2+ in matched primary or recurrent/metastatic tumor samples from January 2010 to June 2022 in our institute were included to evaluate the evolution from or to HER2-2+ expression. Meanwhile, with an emerging of novel entity as HER2-low expression breast cancer, we included this category when analysis as well. Results: In the cohort of a total of 159 breast cancer patients with HER2-2+ expression in either primary tumor or locoregional/distant metastases samples, HER2-2+ breast cancer accounted for 44.0% in primary tumor and 88.8% in recurrent diseases. There were 18.5% and 15.2% patients with HER2 gene amplification on ISH assay among primary and recurrent/metastatic HER2-2+ breast cancers, respectively. The overall rate of HER2 IHC discordance was 67.1%. Among primary HER2-2+ cases, 74.6% maintained in HER2-2+ when disease relapsed. Discordance was mostly driven by cases switching from HER2-2+ to HER2-1+ (64.7%). In HER2-2+ recurrent/metastatic cases, discordance was mostly driven by cases switching from HER2-0 to HER2-2+ (47.1%). The proportion of HER2 discordant cases got a higher statistically trend among HR-positive patients in compared with HR-negative patients (44.1% vs. 21.7%, p = 0.062). There were 35.0% in primary HR-positive/HER2-negative patients and 11.8% in primary triple-negative patients switching from HER2-0 to HER2-low when disease progressed, respectively. Meanwhile, HER2 discordance rate had a significant difference across different metastatic sites (p = 0.026). All contralateral breast and skin metastasis presented with discordant HER2 results. While, all central nervous system metastasis maintained the same HER2-low expression. HER2-positive phenotype in primary breast cancer samples loss their positivity in 42.1% cases. There was a total of 6.6% cases gained HER2 positivity in recurrent breast cancer samples. Conclusion: HER2 expression from primary to relapse breast cancer samples were highly unstable. Biopsy of recurrent sites was necessary to find novel treatment. Citation Format: Anjie Zhu, Hui-Ping Li. HER2 status presented an unstable switching from primary to recurrent breast cancer [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 PO2-05-13.

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