The breast is a complex organ with functional and supportive tissues. The functional components, the lobules and ducts, produce and transport milk and are embedded within a supportive framework known as the breast stroma. This stroma acts as the scaffolding of the breast, providing shape and housing the systems that maintain the organ’s health. It is an active and responsive tissue that surrounds the glandular elements, not merely passive filler.
Composition and Structure of Breast Stroma
The breast stroma is composed of two main types of tissue: fibrous connective tissue and adipose tissue. The fibrous component provides strength and structure through a mix of cells and an extracellular matrix. The primary cells within this fibrous network are fibroblasts, which produce and maintain the matrix by secreting proteins like collagen and elastin. Collagen provides tensile strength, while elastin allows the tissue to stretch and return to its shape.
This fibrous tissue also condenses to form the suspensory ligaments of Cooper. These ligaments are bands of fibrous tissue that traverse the breast from the underlying chest muscles to the skin, helping to support the breast’s weight. The stroma is further organized into two types: a dense interlobular stroma surrounding the larger ducts and lobules, and a specialized intralobular stroma within the lobules.
The second component of the stroma is adipose tissue, or fat, made up of cells called adipocytes. This tissue constitutes the mammary fat pad, which accounts for a significant portion of the breast’s volume and contour. The epithelial network of ducts and lobules is embedded within this fatty stroma, which also contains an extensive network of blood vessels and lymphatic channels that supply nutrients and remove waste.
The Role of Stroma in Normal Breast Function
The stroma provides more than a physical scaffold; it is an active participant in the breast’s normal physiological processes. Its components create a microenvironment that supports the glandular epithelium. The vascular and lymphatic networks within the stroma deliver hormones and nutrients to the epithelial cells and provide a pathway for immune cells to monitor the tissue. This supply and surveillance are necessary for routine tissue maintenance.
An important aspect of the stroma’s role is its dynamic communication with the epithelial cells of the ducts and lobules. This bidirectional interaction, called “crosstalk,” involves the exchange of chemical signals like locally produced growth factors between the stromal and epithelial cells. This communication helps regulate normal cell behavior, including growth and differentiation, ensuring the tissue remains stable.
This interactive nature is most evident in how the stroma responds to hormonal changes. During puberty, systemic hormones like estrogen stimulate the growth of the ductal system, a process dependent on the stroma’s response. Stromal cells have receptors for hormones, including estrogen and growth hormone, that mediate this development as the stroma remodels to accommodate the growing structures.
These changes continue with the menstrual cycle, as fluctuating levels of estrogen and progesterone cause cyclical changes in the breast tissue. During pregnancy and lactation, the stroma undergoes profound changes to support the extensive growth of the lobules needed for milk production. Following menopause, as hormone levels decline, the glandular epithelium tends to regress, and the stroma becomes more composed of adipose tissue.
Stromal Involvement in Breast Conditions
The stroma’s interactive role continues in the context of disease, where it becomes a component of the tumor microenvironment. When cancerous cells develop within the epithelial ducts or lobules, they do not grow in isolation. They engage in a complex interplay with the surrounding stroma, often “recruiting” its cells to support tumor development, which can influence how a cancer grows and spreads.
In response to signals from cancer cells, normal resident fibroblasts can transform into cancer-associated fibroblasts (CAFs). These CAFs are abundant in the stroma of many breast cancers and behave differently than normal fibroblasts. They can promote tumor progression by secreting growth factors, releasing enzymes that break down the tissue matrix to facilitate invasion, and promoting angiogenesis, the formation of new blood vessels to supply the tumor. This process, where the stroma becomes dense and fibrous, is known as a desmoplastic reaction.
While the stroma often reacts to cancers arising from epithelial cells (carcinomas), it can also be the primary tissue of origin for certain breast tumors. These stromal tumors are different from the more common ductal or lobular carcinomas and are classified as fibroepithelial lesions or sarcomas. They are much less common, accounting for a small fraction of all breast neoplasms.
Among the most common of these is the fibroadenoma, a benign tumor composed of both stromal and epithelial elements. Fibroadenomas are found in younger women, are non-cancerous, and do not increase cancer risk. Distinct from these are phyllodes tumors, which are rare fibroepithelial tumors characterized by their leaf-like growth pattern and an increased number of stromal cells. Phyllodes tumors are graded as benign, borderline, or malignant and have a tendency to recur if not completely removed. The rarest stromal tumors are primary breast sarcomas, which are malignant tumors that arise purely from the connective tissue of the stroma and contain no epithelial cells.