Abstract

Abstract Purpose Capecitabine is one of a treatment option in anthracycline and taxane pre-treated metastatic breast cancer (MBC) patients. We have performed miRNA microarray of durable and poor responders to capcitabine, and compared with cell line miRNA expression profile (MCF-7, tamoxifen-resistant MCF-7 [MCF-TAM] cell line treated with 5-FU. Methods Between Jan 2006 to Jan 2021, 66 patients treated with capecitabine after anthracycline and taxane failure were enrolled. Twenty-three archival tumor tissues (11 durables and 12 poor responders, each) were collected and went through nCounter miRNA expression assay. MCF-7, tamoxifen resistant MCF-7 (MCF-TAM) cell line was treated with tamoxifen or 5-FU for proliferation assay and also went through nCounter miRNA expression assay. Results HR positive patients who received anti-estrogen treatment before capecitabine showed longer PFS (median 7.7 vs. 4.03 months, P=0.006). MCF-7 treated with tamoxifen and 5-FU showed decreased proliferation compared to 5-FU treated MCF-7. There was significant difference of miR-579-3p expression between durable and poor responders (log2FC -3.02, P=0.004). Tamoxifen-treated MCF-7 cell line showed upregulation of miR-579-3p compared to MCF-7. Tamoxifen + 5-FU treated MCF-7 cell line showed decreased expression of miR-579-3p compared to 5-FU treated MCF-7 cell line. MCF-7 cell line was treated with 5-FU and miR-579-3p. Compared to 5-FU only treated cell line, 5-FU + miR-579-3p treated cell line showed trends for decreased cell proliferation, suggesting that miR-579-3p may have chemo-sensitizing role during systemic chemotherapy. Based on miRNA database, authors hypothesized that MDM2 may be target protein of miR-579-3p and planning to perform further analysis. Conclusions Anti-estrogen treatment before capecitabine administration was associated to better survival in HR positive MBC. Anti-estrogen potentiated the effect of 5-FU in MCF-7. MiR-579-3p was upregulated in durable responders and tamoxifen treated MCF-7 cell line. Further study is planned to analyze the role of miR-579-3p and its potential target, MDM2 in breast cancer. Citation Format: Jieun Lee, Seung Yeon Joe, Ji-Sun Lee, Dong-Min Kim, Ahwon Lee. Enhanced miR-579-3p by anti-estrogen treatment may affect capecitabine response in hormone receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-10-02.

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