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

Garrett F Beeghly,Jennifer M Munson,Candace Thomas,Jessica X Yuan,Alexandra R Harris

doi:10.3390/bioengineering9020044

Garrett F Beeghly, Jennifer M Munson + Show 3 more

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https://doi.org/10.3390/bioengineering9020044

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Abstract

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.

Highlights

IntroductionThe five-year survival rate for women with breast cancer has improved over the past three decades, rising to 91% on average and 99% for patients with early-stage disease due to improved screening and advances in treatment [1]
One significant achievement of modern medicine is the extent of public and institutional support afforded to women with breast cancer in the United States
The five-year survival rate for women with breast cancer has improved over the past three decades, rising to 91% on average and 99% for patients with early-stage disease due to improved screening and advances in treatment [1]. This continuous increase in survival rate has led to a surge in the number of breast cancer survivors living in the United States, with the figure currently estimated at 3.9 million women

Summary

Introduction

The five-year survival rate for women with breast cancer has improved over the past three decades, rising to 91% on average and 99% for patients with early-stage disease due to improved screening and advances in treatment [1] This continuous increase in survival rate has led to a surge in the number of breast cancer survivors living in the United States, with the figure currently estimated at 3.9 million women. Distant recurrence to the brain is associated with the shortest survival time and poorest prognosis compared with other sites of spread, with the time from diagnosis until death taking just 17 months on average Given this rapidly expanding high-risk population, the current standard of care for the management of metastatic breast cancer needs to be reassessed in order to meet the needs of breast cancer survivors living in remission

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