In a recent article, Kronowitz et al.1 presented results of a matched case-control study of breast cancer patients treated with total or segmental mastectomies: 719 underwent lipofilling and 670 did not. Three hundred five women who underwent lipofilling after risk-reducing mastectomy of cancer-free breast(s) were also followed to assess their risk of developing primary breast cancer. Locoregional recurrences were observed in 1.3 percent of patients (0.25 cases per 100 person-years) in the lipofilling group and 2.4 percent (0.65 cases per 100 person-years) in the control group. Breast cancer did not develop in cancer-free breasts. The authors concluded that these findings support the oncologic safety of lipofilling in breast reconstruction and that lipofilling in breast cancer risk reduction did not stimulate local cancer. These results should be evaluated carefully, as they bring about a strong reassurance of the safety of lipofilling despite the numerous experimental reports showing a stimulation of breast cancer recurrences and metastases after lipofilling in animal studies.
As it would be mostly impossible to set up a randomized trial because lipofilling is subjectively chosen by the patient herself, the matched case-control design is the second best methodology for assessing the safety of lipofilling in breast cancer patients. However, the matching of the two populations and the comparison of event rates in the two groups should be performed very carefully to avoid bias.
Several remarks should be made about the study. As emphasized by the authors, several differences were present in the matching of the two groups: the length of follow-up varied between the two groups (60 months versus 44 months; p < 0.001), and the control group contained more patients with advanced stage (p < 0.001) or HER2/neu+ tumors (p = 0.001), characteristics that could be partly responsible for the higher locoregional recurrence rate observed in this group.
Lipofilling was performed at varying time intervals after oncologic surgery, and time-dependent Cox proportional regression was used to assess its effect on locoregional recurrence. No information was given about eventual locoregional recurrences observed before lipofilling, and whether they counted as events in the lipofilling group, because analysis started after mastectomy. Also, the hazard of locoregional recurrence is expected to be higher in the first years after mastectomy and to decline afterward.2 In the study by Kronowitz et al., mastectomies were performed from 1981 to 2013 and lipofilling was performed from 2001 to 2014, implying that in a few cases lipofilling was delayed by 20 years. The mean interval between mastectomy and lipofilling was 31.5 ± 41.3 months (Table 1). The lower locoregional recurrence rate in the lipofilling group could be attributable in part to the delay from mastectomy.
It is also surprising to find no locoregional recurrences in the 108 cases of carcinoma in situ after 5 years’ median follow-up compared with 5.4 percent in the 61 controls. This is in contrast with the literature, which shows a higher risk of locoregional recurrence in carcinoma in situ patients than in invasive cancer patients.3 Similarly, the difference of locoregional recurrence in the segmental mastectomy seems underestimated in the study group or overestimated in the controls (1.3 percent versus 5.5 percent).4 Finally, the authors mentioned that their findings were similar to those published by Brenelli et al.5 despite the locoregional recurrence rate in this study being 5-fold higher (1.4 percent/year versus 0.25 percent/year).
Although the results of this important study are questionable because of bias in the matching population, the overall results of local or distant events in the lipofilling study group are dramatically low and bring about an argument regarding the safety of lipofilling in breast cancer patients in contradiction to the experimental literature. Further matched controlled studies are still required to confirm these results.
The authors have no financial interest to declare in relation to the content of this communication.
Jean Yves Petit, M.D.
Division of Plastic and Reconstructive Surgery
Patrick Maisonneuve, Dipl.Eng.
Division of Epidemiology and Biostatistics
European Institute of Oncology
1. Kronowitz SJ, Mandujano CC, Liu J, et al. Lipofilling of the breast does not increase the risk of recurrence of breast cancer: A matched controlled study. Plast Reconstr Surg. 2016;137:385393.
2. Nielsen HM, Overgaard M, Grau C, Jensen AR, Overgaard J. Danish Breast Cancer Cooperative Group; Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: Long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies. J Clin Oncol. 2006;24:22682275.
3. Guerrieri-Gonzaga A, Botteri E, Rotmensz N, et al. Ductal intraepithelial neoplasia: Postsurgical outcome for 1,267 women cared for in one single institution over 10 years. Oncologist 2009;14:201212.
4. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347:12271232.
5. Brenelli F, Rietjens M, De Lorenzi F, et al. Oncological safety of autologous fat grafting after breast conservative treatment: A prospective evaluation. Breast J. 2014;20:159165.
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