Intratumor heterogeneity in breast cancer: Tracing its origins and translating findings into clinical practice

Abstract

Breast cancer is well known for its significant heterogeneity, and numerous studies have focused primarily on intertumor heterogeneity. However, increasing evidence highlights the critical role of intratumor heterogeneity (ITH), a complex phenomenon driven by multiple factors in breast cancer progression and treatment. Some studies have demonstrated that higher levels of ITH in breast cancer patients are associated with poor prognosis, but addressing this phenomenon holds potential benefits. In this review, we discuss the origins of ITH, including clonal evolution and cancer stem cell (CSC) models, and the influence of external factors such as the tumor microenvironment and metabolic reprogramming. We also summarize current methods for assessing ITH and potential therapeutic approaches. Understanding ITH can improve diagnostic accuracy and provide a basis for personalized treatment strategies. • High intratumor heterogeneity in breast cancer links to aggressive disease and treatment resistance, worsening prognosis. • Clonal evolution, cancer stem cells, and the tumor microenvironment drive diverse tumor cell populations. • Addressing ITH boosts diagnostic accuracy and aids in creating personalized treatments, improving outcomes.