Cell Fate Decisions During Breast Cancer Development

Abstract

During the formation of breast cancer, many genes become altered as cells evolve progressively from normal to a pre-malignant to a malignant state of growth. How mutations in genes lead to specific subtypes of human breast cancer is only partially understood. Here we review how initial genetic or epigenetic alterations within mammary epithelial cells (MECs) can alter cell fate decisions and put pre-malignant cells on a path towards cancer development with specific phenotypes. Understanding the early stages of breast cancer initiation and progression and how normal developmental processes are hijacked during transformation has significant implications for improving early detection and prevention of breast cancer. In addition, insights gleaned from this understanding may also be important for developing subtype-specific treatment options.

Keywords: breast cancer; cancer heterogeneity; cell fate; mammary epithelial cells; mammary gland; plasticity.

Figure 1

Schematic models of origins of breast cancer heterogeneity (a) Model I posits that mutations associated with neoplastic transformation determine subtype; (b) Model II posits that the cell-of-origin identity determines subtype during neoplastic transformation; (c) Model III posits that both mutation-of-origin and cell-of-origin contribute to the path of disease progression in regards to subtype development.