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Discussion: Fat Grafting after Invasive Breast Cancer: A Matched Case-Control Study.

www.PRSJournal.com 1297 A to the American Society of Plastic Surgeons, there were 27,862 fat grafting procedures for breast reconstruction performed in the United States in 2015.1 Given this increasing use of fat grafting to the breast, the issue of cancer risk is especially topical. “Fat Grafting after Invasive Breast Cancer: A Matched Case-Control Study” is the latest in a series of studies by the authors to evaluate the oncologic risk of breast cancer following fat grafting in breast reconstruction patients.2–5 This article serves as a follow-up to an earlier study, in which the authors found a higher risk of locoregional recurrence in select patients with intraepithelial neoplasia who underwent fat grafting.3 The theoretical basis for heightened oncologic stimulation comes from a host of experimental studies, which have found intimate relationships between adipocytes and mediators such as adipokines.6–11 These interactions have, in turn, been found to promote tumor cell activation and proliferation by varying pathways, including secondary induction of fibroblasts and other stromal cells into tumor-enhancing agents11,12; direct intercellular contact resulting in transcriptional activation of tumor-promoting phenotypes13; stimulation of tumor-specific angiogenesis from the mechanical trauma and wound healing cascade induced by the physical process of fat grafting14; and the transformation of adipose-derived stem cells within the graft itself.13,15 However, the lines of evidence between experimental and clinical studies of fat grafting appear to diverge. Despite the caveats produced by the legion of experimental data on fat cells and tumorigenesis, clinical analysis has not demonstrated an enhanced risk of local recurrence following fat grafting. That being said, most of these aforementioned studies have been plagued by small sample sizes, shorter follow-up, and a retrospective design.9,10,16–22 Given the risk for persistent cancer cells following lumpectomy, the experimentally based concern for interactions between native breast and fat grafted cell has been heightened relevance. Indeed, the majority of the studies looking at oncologic safety with fat grafting have focused on postmastectomy patients.2–4,17,20,23,24 Some native antipathy toward fat grafting in the setting of breast conservation therapy comes from the following: (1) the experimentally based and theoretical oncologic risk; (2) the diminished acuity and magnitude of the reconstructive defect in breast conservation therapy; and (3) the patterns of referral for breast conservation therapy deformities that are less established from breast surgeon to reconstructive surgeon (in the United States at least). With this study, Petit et al. provide a more robust analysis of this question than any preceding investigation. With a mean follow-up of 4.8 years for the fat-grafting cohort and 4.4 years for the control group, the treatment and control groups are well matched for critical oncologic parameters such as age, size of tumor, estrogen receptor status, Ki-67 proliferative labeling index, HER-2 expression status, and chemoradiation protocols.2 The progression of disease-free survival and overall survival using Kaplan-Meier graphs shows no difference in the two cohorts (Fig. 1),2 and the event rate for all oncologic events shows reasonable similitude (Table 2).2 This study provides the strongest evidence to date of the fitness of performing fat grafting in breast conservation therapy patients. However, this is only one study, and the potential for bias in the post hoc analysis cannot be dismissed. Looking more closely at Petit’s earlier study, there were 125 matched patients from 1997 to 2008 who had lipofilling performed (in the context of an overall 38.9 percent rate of breast conservation therapy).4 Their recent study has patients from overlapping