Abstract C065: Kinesin family member C1 (KIFC1/HSET) underlies aggressive disease course in androgen receptor-low triple negative breast cancers

Abstract

Abstract Quadruple negative breast cancer (QNBC), which refers to triple negative breast cancers (TNBCs) lacking androgen receptor (AR) expression, is now considered to be a highly aggressive BC subtype, with no actionable therapeutic targets. QNBC disproportionately afflicts and impacts patients of African descent. Kinesin family member C1 (KIFC1/HSET), a centrosome clustering protein that prevents cancer cells from undergoing centrosome amplification-induced apoptosis, has been reported to be upregulated in TNBCs and African-American (AA) TNBCs, compared to non-TNBCs and European-American (EA) TNBCs. Herein, we analyzed KIFC1 mRNA levels and their associations with clinical features and outcomes among AR-low and AR-high TNBC patients in three distinct publicly-available gene expression datasets and the Breast cancer gene expression database (bc-GenExMiner). We discovered that KIFC1 levels were significantly higher (p<0.05) in AR-low and basal-like TNBCs compared to AR-high and luminal androgen receptor TNBCs, irrespective of stage, grade, tumor size, and lymph node status. We also observed that KIFC1 levels were upregulated in AR-low versus AR-high black and premenopausal TNBC patients (p<0.05). Furthermore, AR levels negatively correlated with KIFC1 levels among TNBC and basal-like TNBC patients (p<0.0001). High KIFC1 levels conferred significantly shorter overall survival (OS), disease-free survival, and distant metastasis-free survival among AR-low and basal-like TNBC patients in Kaplan-Meier analyses (p<0.05). In conclusion, KIFC1 levels may be upregulated in QNBCs and specifically QNBCs of African descent, wherein it may promote poorer outcomes. In addition, therapeutically targeting KIFC1 in these patient subpopulations could significantly mitigate racial disparities in TNBC outcomes. Citation Format: Nikita Wright, Yuan Yate-Ching, Tijana Talisman, Rama Natarajan, Mark LaBarge, Padmashree Rida, Victoria Seewaldt. Kinesin family member C1 (KIFC1/HSET) underlies aggressive disease course in androgen receptor-low triple negative breast cancers [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C065.