Safety of Lipofilling in Breast Cancer Patients

Petit JY, Maisonneuve P, Rotmensz N, Bertolini F, Clough KB,

Sarfati I, Gale KL, Macmillan D, Rey PC, Rietjens M

Introduction

Lipotransfer is a true technical revolution in plastic surgery and is increasingly used worldwide. Although known since several decades, the lipofilling has been indicated more recently in breast cancer patients to improve the results of breast reconstructions and to correct deformities after conservative treatment.  A number of publications in plastic surgery literature underline the versatility of the technique and the quality of the results (1-8). They underline the efficacy of the lipofilling as a cosmetic procedure and consider it as a safe oncological only as a neutral biological material able to restore the body contour. Several studies underline the power of the transferred fat to regenerate the blood supply of the skin disorders after radiotherapy (9,10). Such active regeneration of the tissue can be explained by the presence of a high percentage of progenitor cells included in the fat tissue (11).  Attention should be drawn to the recent and abundant preclinical studies which mention that adipose progenitor cells may promote breast cancer growth and metastasis. As recently shown, white adipose tissue (WAT)-derived progenitor cells can contribute to tumour vessels, pericytes and adipocytes, and were found to stimulate local and metastatic progression of breast cancer in several murine models (12-14). Experimental studies provide data on the endocrine, paracrine, and autocrine activity of the transplanted fat tissue (15). Adipocyte, pre-adipocyte and progenitor cells production of adipokines and several other secretions, can stimulate angiogenesis and growth of breast cancerous cells (16). The “tumour-stroma interaction” can potentially induce cancer reappearance by “fuelling” dormant breast cancer cells in tumour bed (17). Clinically, there is a case showing a local recurrence more than 13 years after apparent cure of an osteosarcoma, one year after a lipofilling of the shoulder for cosmetic repair (18). Moreover, a case-control study revealed a significant increase of local recurrences in intra-epithelial breast cancer patients who underwent a lipofilling procedure for breast reconstruction (19,20).  

Concern about radiologic sequelae and surveillance difficulties by mammography due to lipofilling has led to an important literature. The risk of calcifications observed after lipofilling has provoked discussions concerning diagnosis of recurrences. This issue has largely been resolved by the distinction between true micro calcifications and macro calcifications related to fat necrosis as observed in most cases after fat transfer. Such images can easily be distinguished from suspicious calcifications (3,21,22).
In order to confirm the safety of lipofilling procedure in breast cancer patients, clinical studies based on adequate statistical method and accurate follow-up are required to demonstrate that the local recurrence rate as well as any cancer event is not increased in the fat grafted breast cancer patients.

Discussion

The three studies Milan, Paris, and Nottingham are homogenous in what concerns the technique of lipofilling all of them using the Coleman technique. MacMillan in Nottingham analysed his personal result after lipotransfer in breast cancer patients in a case-control study (article in press). He did not observe an increased number of local recurrences in the in situ group as we observed in Milan and in Paris. But in his series, the number of in situ cases was probably too small to show a difference. However, the trend in the last Milan study is a disappearance of the significant difference between study group and the control group due to an increase of LR in the controls with a longer follow up. When we gather the cases of the three studies dealing with the Coleman technique, in order to get more statistical power, no more significant increase of LR is observed. The strength of the Milan studies and the Nottingham study is the quality of the comparison using precise match criteria. One of the difficulty to match the populations was the risk of bias due to the great variety of lapse time between the primary surgery (cancer treatment) and the date of the lipofilling. The study-population has been selected among the cases which did not have a cancer event during this lapse-time. The lipo-filled patients received their fat transfer at a different time after the cancer treatment and the length of the disease free period modifies the local recurrence risk after the lipofilling. Therefore, it was necessary to match the controls according to the length of the different lapse-time between primary surgery and lipofilling. The weakness of these studies is the population size of the intra-epithelial cancers: 59 patients in the Milan study and 27 in Nottingham study. The short follow up of the series was also an important critic: around two years after the lipofilling. The last review of the Milan study showed a disappearance of the significant difference. Systematic review dedicated to the “Safety of Autologous Lipoaspirate Grafting in Breast Cancer Patients“, Krastev and collaborators analysed 394 articles dealing with fat transfer (31). After selection according to the content of cancer data, the quality of the follow up, the size of the series, the authors focused only 9 articles reaching the cancer criteria requirements. Among these 9 papers, they found no prospective study and no randomized trials. Only two retrospective studies were found to have a control group. One of Rigotti (9) compared the local recurrence rate of 133 mastectomy cases with lipofilling during the period pre and post lipofilling. No increase was observed and Rigotti concluded that lipofilling is a safe procedure in cancer patients aiming that if lipofilling was detrimental oncologically, the rate of recurrences in the second period post lipofilling should have been increased. Two critics have been made concerning the statistical methodology of the study (32). One was the exclusion of the breast conservative treatments which are patients with higher risk of cancer cells remaining in the breast after the treatment. The second deals with the methodology: the comparison between LR rate before and after the lipofilling could be reliable only if the actuarial rate of LR after the primary surgery was following a straight line. It is usually stated that the rate of recurrence is higher in the first 5 years and then reach a plateau. Finally, Krastev concluded: “Whether lipoaspirate grafting promotes LRR in breast cancer patients is still unclear. To be able to answer this question, larger prospective trials with longer follow-up are needed.” Other reviews concluded also that further prospective studies are needed to confirm the safety of lipofilling in breast cancer patients (33-36). Therefore, it will be extremely important to get more oncologic results after using the enrichment technique. The analysis of the literature showed that the progenitor cells should be responsible for the stimulation of remaining cancer cells, their concentration obtained thanks to the enrichment technique could stimulate the risk of cancer recurrences. We did not find reliable studies demonstrating the safety of enriched lipofilling in breast cancer patients. Although the “Restore study” published in 2012 did not find any recurrence in the series of 67 patients after a follow up of one year. The weakness of these results is the size of the study group, the lack of controls and the short follow up (37).

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