Pregnancy has a dual effect on the risk of breast cancer. On one hand, pregnancy at a young age is known to be protective. However, pregnancy is also associated with a transient increased risk of breast cancer. For women that have children after the age of 30, the risk remains higher than women who never had children for decades. Involution of the breast has been identified as a window of mammary development associated with the adverse effect of pregnancy. In this review, we summarize the current understanding of the role of involution and describe the role of collagen in this setting. We also discuss the role of a collagen-dependent protease, pappalysin-1, in postpartum breast cancer and its role in activating both insulin-like growth factor signaling and discoidin domain collagen receptor 2, DDR2. Together, these novel advances in our understanding of postpartum breast cancer open the way to targeted therapies against this aggressive breast cancer sub-type.
Keywords: Collagen; DDR2; Involution; PAPP-A; Postpartum breast cancer; Pregnancy-associated breast cancer.