Designing Patient-Driven, Tissue-Engineered Models of Primary and Metastatic Breast Cancer

The rising survival rate for early-stage breast cancer in the United States has created an expanding population of women in remission at risk for distant recurrence, with metastatic spread to the brain demonstrating an especially poor prognosis. The current standard of care for breast cancer brain metastases is not well defined or differentiated from the treatment of brain metastases from other primary sites. Here, we present tissue-engineered models of the primary and brain metastatic breast cancer microenvironments informed by analysis of patient tumor resections. We find that metastatic resections demonstrate distinct cellular and matrix components compared with primary resections or non-cancerous controls. Using our model systems, we find that the observed deposition of collagen I after metastasis to the brain may enhance breast cancer invasion. Future optimization of these models will present a novel platform to examine tumor-stroma interactions and screen therapeutics for the management of metastatic breast cancer.

Automated summary

The rising survival rate of early-stage breast cancer in the United States has led to an increasing population of women in remission at risk for distant recurrence, with brain metastases showing a particularly poor prognosis. Tissue-engineered models based on patient tumor resections have revealed distinct cellular and matrix components in brain metastases compared to primary resections or non-cancerous controls. The observed deposition of collagen I after brain metastasis in their models suggests a potential enhancement of breast cancer invasion, providing a novel platform for studying tumor-stroma interactions and therapeutic screening for metastatic breast cancer management.