Lipofilling Reduces Dormant Breast Cancer Outgrowth as Opposed to Adipocutaneous Flap Controls in a New Murine Model of Postlumpectomy Breast Reconstruction

摘要

The transfer of autologous tissue is nowadays considered the gold standard of breast reconstruction. To this end, fat grafting and flap transfer represent the 2 most common approaches. However, important concerns regarding the oncological safety of fat grafting remain unanswered. In this context, satisfactory experimental models of autologous lipofilling techniques have not been described in the literature so far. Hence, the in vivo impact of both autologous tissue transfer approaches on the outgrowth of dormant breast cancer cells retained within the surgical field has so far not been assessed experimentally. Therefore, we devised a new experimental model of lipofilling in immunocompetent mice. As part of our pilot study, murine lipoaspirates were analyzed and compared to adipocutaneous flaps regarding their cellular viability via Calcein AM labelling, volume retention as derived by longitudinal magnetic resonance imaging, hypoxic stress according to the Hypoxyprobe assay, angiogenesis by means of CD-31 positive vessel counts, proliferation as deduced from the Ki-67 index, and immune cell infiltration upon conventional hematoxylin and eosin staining. Lipografts were found to remain viable for over 30 days post transfer and showed long-term volume retentions of approximately 40%. We discovered significantly higher initial levels of hypoxia and proliferation, as well as significantly increased vessel counts, and marked macrophage infiltrates in fat grafted specimens compared to adipocutaneous flaps. Subsequently, orthotopically implanted syngeneic D2.0R dormant breast cancer cells were exposed to either tissue transfer method in our newly established murine model in order to assess their impact on tumor outgrowth kinetics in vivo. Interestingly, all animals with adipocutaneous flaps developed mammary tumors at the same rate as baseline controls. On the contrary, only 20% of all lipografted animals developed tumors at a later point in time. In summary, our new immunocompetent murine model of lipofilling is an important addition to the repertory of experimental approaches to autologous breast reconstruction. Furthermore, our data suggest that fat grafting does not fuel local recurrence of dormant breast cancer cells in mice. Quite the contrary, it may even have a suppressive effect.