Causes of Chording Phenomenon in Breast Cancer
The chording phenomenon in breast cancer is primarily caused by increased collagen deposition and extracellular matrix (ECM) stiffening in the breast tissue, which creates cord-like structures that contribute to tumor progression and invasion.
Extracellular Matrix Changes
- Increased peri-ductal collagen micro-organization is a key factor in the development of chording phenomenon, creating dense fibrous bands in breast tissue 1
- High mammographic density, which correlates with chording, is associated with increased stromal collagen and immune cell infiltration within the mammary epithelium 2
- Dense breast stromal tissue shows greatly increased concentration of breast epithelium, contributing to the formation of chord-like structures 3
Molecular Mechanisms
- Collagen density promotes mammary tumor initiation and progression through the formation of rigid, chord-like structures that facilitate cancer cell invasion 4
- Stromal PDGFR-α activation enhances matrix stiffness, impeding normal mammary ductal development and accelerating tumor growth through the formation of chord-like pathways 5
- Human breast cancer invasion and aggression directly correlates with ECM stiffening, which creates the physical manifestation of chording [@17@]
Tumor Microenvironment Factors
- Cancer-associated fibroblasts induce epithelial-mesenchymal transition of breast cancer cells through paracrine TGF-beta signaling, contributing to the formation of chord-like structures 6
- The tumor microenvironment progression is influenced by stromal changes that create the physical manifestation of chording 7
- Matrix density-induced mechanoregulation of breast cell phenotype occurs through a FAK-ERK linkage, which promotes the development of chord-like structures [@21@]
Clinical Implications
- Tensional homeostasis alterations in the malignant phenotype lead to the formation of chord-like structures that can be felt on clinical examination [@20@]
- Force engagement of vinculin promotes tumor progression by enhancing PI3K activation, contributing to the physical manifestation of chording [@22@]
- Evidence suggests that breast tissue stiffness, which manifests as chording, is associated with increased risk of breast cancer [@19@]
Prevention and Management Considerations
- Addressing factors that contribute to increased mammographic density may help reduce the development of chording phenomenon [@23@]
- Early intervention targeting the extracellular matrix components may help prevent the progression of chord formation in breast cancer patients 4
- Understanding the molecular mechanisms behind chording can lead to targeted therapies that disrupt this process and potentially improve outcomes [@21@, @22@]