Dynamic Extracellular Matrix Remodeling and Immune Reprogramming in the Postpartum Mammary Gland: Implications for Maternal Health and Breast Cancer Risk

Abstract

The mammary gland is a uniquely dynamic organ, undergoing profound structural and functional transformations throughout the pregnancy- lactation-involution cycle. These changes are orchestrated by a complex interplay between systemic hormones and the local microenvironment. Recent studies identify the extracellular matrix (ECM) and the innate immune landscape as critical determinants of both physiological tissue homeostasis and pathological progression. Postpartum breast cancer (PPBC), defined as breast cancer diagnosed within ten years following childbirth, represents a distinct clinical entity characterized by increased aggressiveness, higher metastatic potential, and poor prognosis. This review provides a comprehensive synthesis of recent updates in mammary gland biology, focusing on the triphasic pattern of collagen regulation, the role of matrix metalloproteinases (MMPs) and lysyl oxidase (LOX) in tissue remodeling, and the emergence of an immunosuppressive "wound-healing" environment during involution. We explore molecular regulatory nodes, including microRNAs and calpains, and the impact of environmental exposures on breast tissue composition. By integrating data derived from high-resolution spatial profiling and single-cell transcriptomic analyses, this article aims to provide an understanding of how the postpartum mammary microenvironment supports tumorigenesis, highlighting potential biomarkers and therapeutic targets to improve maternal health outcomes