BCAR4 Expression as a Predictive Biomarker for Endocrine Therapy Resistance in Breast Cancer

• Published in: Clinical breast cancer 2024-06, Vol.24 (4), p.368-375.e2
• Main Authors: Liao, Muheng, Webster, Jace, Coonrod, Emily M., Weilbaecher, Katherine N., Maher, Christopher A., White, Nicole M.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Hormonal - pharmacology; Antineoplastic Agents, Hormonal - therapeutic use; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Drug resistance; Drug Resistance, Neoplasm - genetics; Female; Gene Expression Regulation, Neoplastic; Genomics; Humans; Prognosis; Receptors, Estrogen - metabolism; RNA, Long Noncoding
• ISSN: 1526-8209; 1938-0666; 1938-0666
• DOI: 10.1016/j.clbc.2024.02.007

Breast cancer, particularly the estrogen receptor positive (ER+) subtype, remains a leading cause of cancer-related death among women. Endocrine therapy is the most effective treatment for ER+ breast cancer; however, the development of resistance presents a significant challenge. This study explored the role of the breast cancer antiestrogen resistance 4 (BCAR4) gene as a potential driver of resistance and a pivotal biomarker in breast cancer. The researchers undertook a comprehensive analysis of 1743 patients spanning 6 independent cohorts. They examined the association of BCAR4 expression with patient outcomes across all breast cancer types and the PAM50 molecular subtypes. The relationship between elevated BCAR4 expression and resistance to endocrine therapy including AIs, the prevailing standard-of-care for endocrine therapy, was also investigated. This meta-analysis corroborated the link between BCAR4 expression and adverse outcomes as well as resistance to endocrine therapy in breast cancer. Notably, BCAR4 expression is clinically significant in luminal A and B subtypes. Additionally, an association between BCAR4 expression and resistance to AI treatment was discerned. This study expands on previous findings by demonstrating that BCAR4 expression is associated with resistance to newer therapies. The identification of patients with intrinsic resistance to hormone therapy is crucial to avoid ineffective treatment strategies. These findings contribute to our understanding of endocrine therapy resistance in breast cancer and could potentially guide the development of more effective treatment strategies. Estrogen receptor positive (ER+) breast cancer is a leading cause of cancer-related deaths among women due to treatment resistance. This study explored the role of the breast cancer antiestrogen resistance 4 (BCAR4) gene as a potential driver of resistance and a pivotal biomarker in breast cancer. Through an extensive study of 1743 patients across 6 cohorts, high BCAR4 expression was found to correlate with poor outcome, particularly in luminal A and B subtypes, with resistance to endocrine therapy including aromatase inhibitor (AI) treatments. These insights enrich our understanding of endocrine therapy resistance and may lead to improved therapeutic strategies.