Autologous fat transfer after breast cancer surgery: An exact-matching study on the long-term oncological safety.

INTRODUCTION: Autologous fat transfer (AFT) is widely adopted for breast reconstruction, but its long-term oncologic safety is still not clearly established. The aim of the present study was to compare the 10-year loco-regional recurrence (LRR)-free and distant metastases (DM)-free survival probabilities in AFT vs. control patients, also evaluating the impact of AFT in different intrinsic molecular subtypes of breast cancer. MATERIALS AND METHODS: 464 AFT patients were exactly matched with a cohort of 3100 control patients treated between 2007 and 2017. A multivariate survival analysis was performed accounting for all variables related to LRR and DM, including adjuvant/neoadjuvant treatments. End-points were analyzed both overall and in each molecular subtype. RESULTS: LRR occurred in 6.4% of AFT and in 5.0% of control patients (p = 0.42), while DM were observed respectively in 7.7% and 5.4% of cases (p = 0.20). AFT showed no effect on the 10-year LRR-free survival probability (adjusted HR 0.87, 95%CI 0.43-1.76, p = 0.69) or the 10-year DM-free survival probability (adjusted HR 0.82, 95%CI 0.43-1.57, p = 0.55). Luminal A patients treated by AFT showed a decreased LRR-free survival probability (HR 2.38, 95%CI 0.91-6.17, Log-Rank p = 0.07), which was significantly lower than controls after 80 months (Log-Rank p = 0.02). No differences in the 10-year event-free survival probability were found in Luminal B, HER2-positive or triple-negative patients. CONCLUSION: AFT does not increase breast cancer recurrence, with the possible exception of late LRRs for Luminal A patients, but further clinical and preclinical data are required to better clarify this data. The use of AFT should not be discouraged.

Adipose-derived Mesenchymal Stem Cells (ASCs) may favour breast cancer recurrence via HGF/c-Met signaling.

Adipose tissue is a reservoir of Mesenchymal Stem Cells (Adipose-derived Mesenchymal Stem Cells, ASCs), endowed with regenerative properties. Fat graft was proposed for breast reconstruction in post-surgery cancer patients achieving good aesthetic results and tissues regeneration. However, recent findings highlight a potential tumorigenic role that ASCs may have in cancer recurrence, raising some concerns about their safety in clinical application. To address this issue, we established a model where autologous ASCs were combined with primary normal or cancer cells from breast of human donors, in order to evaluate potential effects of their interactions, in vitro and in vivo. Surprisingly, we found that ASCs are not tumorigenic per sè, as they are not able to induce a neoplastic transformation of normal mammary cells, however they could exhacerbate tumorigenic behaviour of c-Met-expressing breast cancer cells, creating an inflammatory microenvironment which sustained tumor growth and angiogenesis. Pharmacological c-Met inhibition showed that a HGF/c-Met crosstalk between ASCs and breast cancer cells enhanced tumor cells migration, acquiring a metastatic signature, and sustained tumor self-renewal. The master role of HGF/c-Met pathway in cancer recurrence was further confirmed by c-Met immunostaining in primary breast cancer from human donors, revealing a strong positivity in patients displaying a recurrent pathology after fat grafts and a weak/moderate staining in patients without signs of recurrence. Altogether our findings, for the first time, suggest c-Met expression, as predictive to evaluate risk of cancer recurrence after autologous fat graft in post-surgery breast cancer patients, increasing the safety of fat graft in clinical application.

Short commentaries on data published by Petit et al. on locoregional risk after lipofilling in breast cancer patients.

Lipofilling is becoming part of the breast reshaping after quadrantectomy or mastectomy in breast cancer patients, but there are open questions of its safety.