Abstract 3285: Elevated expression of breast cancer stem cell marker alpha6-integrin is associated with reduced anti-estrogen efficacy in breast cancer

Abstract

Abstract Most women diagnosed with breast cancer have tumors expressing the estrogen receptor and are prescribed agents such as aromatase inhibitors or the anti-estrogens tamoxifen or fulvestrant. However, up to 40% of these patients will experience relapse due to endocrine therapy resistance even when these agents are used in combination with cyclin dependent kinase inhibitors. A small population of cells within tumors known as breast cancer stem cells are generally resistant to endocrine therapy and are believed to promote patient relapse. We previously found that breast cancer stem cell marker α6-integrin is expressed at elevated levels in cells that are resistant to the anti-estrogen tamoxifen. We thus hypothesized that elevated levels of α6-integrin confer resistance to anti-estrogens. Quantitative PCR analyses revealed that tamoxifen-resistant and fulvestrant-resistant mammospheres (breast cancer spheroids) exhibit increased α6-integrin expression as compared to antiestrogen-sensitive mammospheres. Cells with enforced α6-integrin expression were less responsive to tamoxifen and fulvestrant than control cells. Further, pharmacological or genetic inhibition of α6-integrin enhanced anti-estrogen efficacy. Our data suggest that targeting α6-integrin represents a viable strategy to overcome endocrine therapy resistance. Citation Format: Gabriel Viteri, Shawnee Angeloni, Ubaldo Soto, Eileen J. Brantley. Elevated expression of breast cancer stem cell marker alpha6-integrin is associated with reduced anti-estrogen efficacy in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3285.