STEM CELLS Translational Medicine An Animal Model of Local Breast Cancer Recurrence in the Setting of Autologous Fat Grafting for Breast Reconstruction

The rodent model that received fat grafting in the setting of retained tumor was successfully developed. Grafts showed that injection of more cancer cells correlated with bigger tumor masses (A, E). Fat injection had a significant increasing effect on tumor and fibrosis mass (F). Histologically, MDA‐MB‐231 cancer cells are residing and proliferating (B, C, D), but the proliferation index by Ki67 is significantly reduced, suggesting that the fat grafting is associated with downregulation of proliferation in local tumor cells. Scale bar = 200 µm.


Abstract

Autologous fat grafting after breast cancer surgery is commonly performed, but concerns about oncologic risk remain. To model the interaction between fat grafting and breast cancer cells, two approaches were employed. In the first approach, graded numbers of viable MDA‐MB‐231 or BT‐474 cells were admixed directly into human fat grafts and injected subcutaneously into immune‐deficient mice to determine if the healing graft is a supportive environment for the tumor. In the second approach, graded doses of MDA‐MB‐231 cells were suspended in Matrigel and injected into the mammary fat pads of mice. Two weeks after the tumor cells engrafted, 100 μL of human adipose tissue was grafted into the same site. Histologically, MDA‐MB‐231 cells seeded within fat grafts were observed and stained positive for human‐specific pan‐cytokeratin and Ki67. The BT‐474 cells failed to survive when seeded within fat grafts at any dose. In the second approach, MDA‐MB‐231 cells had a strong trend toward lower Ki67 staining at all doses. Regression analysis on all groups with fat grafts and MDA‐MB‐231 revealed fat tissue was associated with lower cancer cell Ki67 staining. Healing fat grafts do not support the epithelial BT‐474 cell growth, and support the mesenchymal MDA‐MB‐231 cell growth only at doses ten times greater than in Matrigel controls. Moreover, fat grafts in association with MDA‐MB‐231 cancer cells already present in the wound resulted in decreased tumor proliferation and increased fibrosis. These findings suggest that clinical fat grafting does not induce breast cancer cell growth, and may even have a suppressive effect. Stem Cells Translational Medicine 2018;7:125–134

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