Understanding and overcoming tumor heterogeneity in metastatic breast cancer treatment

Rational development of targeted therapies has revolutionized metastatic breast cancer outcomes, although resistance to treatment remains a major challenge. Advances in molecular profiling and imaging technologies have provided evidence for the impact of clonal diversity in cancer treatment resistance, through the outgrowth of resistant clones. In this Review, we focus on the genomic processes that drive tumoral heterogeneity and the mechanisms of resistance underlying metastatic breast cancer treatment and discuss implications for future treatment strategies. Pasha and Turner review recent insights into the role of intratumoral heterogeneity in therapeutic resistance in metastatic breast cancer and discuss forward-looking strategies to overcome this hurdle.