Breast cancer is a heterogeneous disease. There is a high degree of diversity between and within tumors as well as among cancer-bearing individuals, and all of these factors together determine the risk of disease progression and therapeutic resistance. Advances in technologies such as whole-genome sequencing and functional viability screens now allow us to analyze tumors at unprecedented depths. However, translating this increasing knowledge into clinical practice remains a challenge in part due to tumor evolution driven by the diversity of cancer cell populations and their microenvironment. The articles in this Review series discuss recent advances in our understanding of breast tumor heterogeneity, therapies tailored based on this knowledge, and future ways of assessing and treating heterogeneous tumors.
Hypothetical model explaining the origins of intertumor and intratumor heterogeneity in breast cancer.
Intratumor heterogeneity is due to the presence of cancer cells with variable phenotypes such as different degrees of basal-like and luminal features. Intertumor heterogeneity may also be explained by the presence of these different cell types within tumors at varying frequencies. Cancer cells with a basal-like phenotype predominate in basal-like tumors, whereas luminal tumors are largely composed of luminal breast cancer cells. However, due to variability in basal-like and luminal cell traits, not all basal-like and luminal tumors are the same, further contributing to heterogeneity even within tumor subtypes.