Hormone Signaling in Breast Development and Cancer

Hormones control normal breast development and function. They also impinge on breast cancer (BC) development and disease progression in direct and indirect ways. The major ovarian hormones, estrogens and progesterone, have long been established as key regulators of mammary gland development in rodents and linked to human disease. However, their roles have been difficult to disentangle because they act on multiple tissues and can act directly and indirectly on different cell types in the breast, and their receptors interact at different levels within the target cell. Estrogens are well-recognized drivers of estrogen receptor-positive (ER+) breast cancers, and the ER is successfully targeted in ER+ disease. The role of progesterone receptor (PR) as a potential target to be activated or inhibited is debated, and androgen receptor (AR) signaling has emerged as a potentially interesting pathway to target on the stage.In this chapter, we discuss hormone signaling in normal breast development and in cancer, with a specific focus on the key sex hormones: estrogen, progesterone, and testosterone. We will highlight the complexities of endocrine control mechanisms at the organismal, tissue, cellular, and molecular levels. As we delve into the mechanisms of action of hormone receptors, their interplay and their context-dependent roles in breast cancer will be discussed. Drawing insights from new preclinical models, we will describe the lessons learned and the current challenges in understanding hormone action in breast cancer.