Abstract PO2-15-09: Immune related cell fraction in peripheral blood and outcomes of advanced breast cancer patients treated with Eribulin
Authors: Nagahashi Masayuki , Bun Ayako , Kuroiwa Mamiko , Komatsu Miki , Urano Sayaka , Fujimoto Yukie , Oshiro Aoi , Mitsuyoshi Ayumu , Kanaoka Haruka , Hattori Akira , Fukui Reiko , Higuchi Tomoko , Nishimukai Arisa , Murase Keiko , Takatsuka Yuichi , Miyoshi Yasuo 
Published: May 2024

Abstract
Background: Eribulin prolongs overall survival (OS) of patients with advanced breast cancer, and an ad-hoc analysis of the EMBRACE trial showed that baseline absolute lymphocyte count (ALC) was a predictor of OS prolongation. It has been suggested that eribulin improves the immune response to the tumor by improving the hypoxic environment through remodeling of local tumor vessels and reducing hypoxic stress, leading to OS prolongation. However, the details of the immune response mediated by eribulin remain to be fully elucidated. CD8+ cells attack cancer cells as cytotoxic T cells, while regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) suppress activated T cells that attack cancer cells. In this study, we focused on CD8+ cytotoxic T cells, Tregs, MDSCs, and CD4-CD25-FoxP3+ cells in peripheral blood, analyzed the changes of those immune cells before and after eribulin treatment, and examined the effects on the outcomes of breast cancer patients. Methods: Nineteen patients with advanced or recurrent breast cancer treated with eribulin from April 2021 to May 2023 at our hospital were included. Peripheral blood was collected before drug administration as the first treatment (pre-treatment) and before drug administration in the second course (post-treatment), and the cell fractions, including CD4+ cells, CD8+ cells, CD4+CD25+FoxP3+ Tregs, CD11b+CD14+CD33+ MDSCs, and CD4-CD25-FoxP3+ cells, were analyzed by flow cytometry. The cutoff value for ALC was set at 1000 and NLR at 3.0, and each cell fraction was set to its respective median. Kaplan-Meier plots and logrank tests for progression-free survival (PFS) or OS were applied. Results: CD4+ cells were significantly lower post-treatment compared to pre-treatment (p=0.0140). Further, Tregs were significantly lower post-treatment compared to pre-treatment (p=0.0258). There were no significant changes in the levels of CD8+ cells, MDSCs, and CD4-CD25-FoxP3+ cells between pre- and post-treatment. We examined the association between each cell fraction and ALC or NLR, and found that CD4-CD25-FoxP3+ cells were significantly higher in cases with high NLR (p=0.0110). Analysis of the association between each cell fraction and prognosis at pre-treatment revealed that the high CD8+ cell group had significantly better PFS and OS than the low CD8+ cell group (p=0.0129 and p=0.0077, respectively). Interestingly, the high CD4-CD25-FoxP3+ cell group had significantly worse PFS than the low CD4-CD25-FoxP3+ cell group (p=0.0026). Conclusion: In the current study, Tregs in the peripheral blood of breast cancer patients significantly decreased after eribulin treatment, suggesting that eribulin may improve the immune microenvironment by suppressing immunosuppressive cells in cancer, including Tregs. In addition, the CD4-CD25-FoxP3+ cell fraction may serve as a biomarker for eribulin therapy, and further studies are needed to elucidate the details, including analysis of the constituent cells within the fraction.
Citation Format: Masayuki Nagahashi, Ayako Bun, Mamiko Kuroiwa, Miki Komatsu, Sayaka Urano, Yukie Fujimoto, Aoi Oshiro, Ayumu Mitsuyoshi, Haruka Kanaoka, Akira Hattori, Reiko Fukui, Tomoko Higuchi, Arisa Nishimukai, Keiko Murase, Yuichi Takatsuka, Yasuo Miyoshi. Immune related cell fraction in peripheral blood and outcomes of advanced breast cancer patients treated with Eribulin [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 PO2-15-09.