Lipofilling of the Breast Does Not Increase the Risk of Recurrence of Breast Cancer

A Matched Controlled Study

Steven J. Kronowitz, M.D.; Cosman Camilo; Mandujano, M.D.; Jun Liu, M.D., Ph.D.; Henry M. Kuerer, M.D., Ph.D.; Benjamin Smith, M.D.; Patrick Garvey, M.D.; Reshma Jagsi, M.D.; Limin Hsu, M.A.; Summer Hanson, M.D.; Vicente Valero, M.D.

Disclosures

Plast Reconstr Surg. 2016;137(2):385-393. 

In This Article

Discussion

In contrast to previous studies that have evaluated the incidence of breast cancer recurrence in breast cancer patients who have undergone lipofilling for breast reconstruction after mastectomy, our study included a control group. In addition, our study included more patients than did previous studies. In our study, we found no significant differences in the rates of locoregional recurrence or systemic recurrence between breasts reconstructed with lipofilling and breasts reconstructed without lipofilling. We also compared rates of locoregional recurrence in breasts reconstructed with and without lipofilling within several subgroups defined on the basis of clinical, pathologic, and lipofilling procedure characteristics, and we found that the only subgroup in which the locoregional recurrence rate was higher for lipofilling was the subgroup treated with hormonal therapy. We also did not find any instances of primary breast cancer development in healthy breasts reconstructed with lipofilling, inclusive of 33 patients who were carriers for the BRCA1/BRCA2 mutation.

The increasing popularity of fat grafting is evidenced by the significant increase in articles being published on the subject. We could find only two articles on fat grafting for breast reconstruction published in 1993, but in 2013, more than 120 articles on this topic were published. Many of the previously reported studies focused on the technical aspects of serial fat grafting, including the number of fat grafting sessions required and the total volume usually used for breast reconstruction.

One study examined the trends in fat grafting through a national survey of members of the American Society of Plastic Surgeons (456 respondents of 2584 members sent the survey).[1] In that study, 62 percent of respondents reported currently using fat grafting for reconstructive breast surgery. Twenty-eight percent of respondents reported currently using fat grafting for aesthetic breast surgery, and 59 percent of respondents had not performed fat grafting for aesthetic breast surgery and had no plans to do so in the future. When asked about potential obstacles to incorporation of fat grafting into clinical practice, 49 percent of respondents strongly agreed or agreed that the lack of evidence concerning the impact of fat grafting to the breast on breast cancer development or recurrence was an obstacle.

To overcome this obstacle so that 100 percent of surgeons can confidently incorporate fat grafting into their clinical practice, we first need to know what occurs physiologically when we inject fat grafts into patients' breasts. Rigotti et al. in 2007 elucidated how lipoaspirate heals irradiated tissue through a process mediated by adipose-derived adult stem cells.[6] Ultrastructural analysis of the lipoaspirate revealed a well-preserved stromal vascular component. However, well-preserved adipocytes were virtually absent. Cytologic characterization of the lipoaspirate by in vitro expansion showed that the mesenchymal stem cells corresponded to bone marrow–derived mesenchymal stem cells. Four to 6 months after injection of the lipoaspirate into the patient, adipocytes were normal, and the microvasculature exhibited normal ultrastructure. One year or more after treatment, the picture was substantially unchanged apart from a tendency toward shrinking extracellular spaces, with normal adipocytes and a well-formed microcirculation. Certainly, this information should guide clinicians to perform serial fat grafting procedures 4 to 6 months apart. In addition, our current study found that the median time from lipofilling to detection of locoregional recurrence (19 months) was not directly related to completion of the maturation process of the vasculature and extracellular space.

Another piece of information we need to confirm the safety of fat grafting is information regarding the interaction between the fat graft and the tumor bed. Hypothetically, the transfer of adipose tissue–derived stem cells or adipose tissue–derived mesenchymal stem cells could induce dormant tumor cells to reproduce and thereby predispose the patient to locoregional recurrence. In vitro and animal studies have produced conflicting findings regarding the impact of stem cells, with some showing positive and others showing negative associations with breast cancer cell proliferation. Petit and colleagues published a retrospective European multi-institutional study of 646 cases of lipofilling of the breast and found, to the concern of many surgeons, that the risk of breast cancer recurrence was higher in patients with in situ carcinoma than in patients with invasive breast cancer.[7] In a follow-up retrospective study (59 patients), Petit et al. focused only on patients with in situ carcinoma of the breast and found that patients who underwent lipofilling had an 18 percent cumulative 5-year risk of locoregional recurrence, compared with a 3 percent cumulative 5-year risk in patients who did not undergo lipofilling.[8] An important factor to consider in both studies by Petit et al. was that a large percentage of patients undergoing breast conserving therapy received only intraoperative radiation therapy.

In contrast to the findings of Petit and colleagues,[7,8] we observed only 25 local regional recurrences (1.5 percent) and total locoregional recurrence incidence rates of 1.3 percent for lipofilling cancer patients and 2.4 percent for no-lipofilling cancer patients. In addition, we found no significant differences in 5-year cumulative locoregional recurrence rate between breast cancer patients with lipofilling (1.6 percent, 0.25 cases per 100 person-years) and breast cancer patients without lipofilling (4.1 percent, 0.65 cases per 100 person-years). Our findings were similar to those in a recent prospective study by Brenelli et al. of 59 patients[9] that found that only three patients (4 percent incidence) had a recurrence of breast cancer, with an estimated annual rate of recurrence of 1.3 percent per year.

Theoretically, segmental mastectomy should be associated with the highest risk of locoregional recurrence after lipofilling because much of the breast tissue is not resected; however, in the previously mentioned prospective study of 59 patients,[9] all three patients with a recurrence of breast cancer had invasive primary tumors and invasive recurrences. In contrast to the studies by Petit et al.[7,8] and in agreement with the 59-patient prospective study,[9] we found no significant differences in the risk of locoregional recurrence between breasts reconstructed with lipofilling and breasts reconstructed without lipofilling in either the invasive breast cancer or intraductal breast cancer subgroups. We found no significant differences in the risk of breast cancer recurrence between breasts treated with segmental mastectomy and breasts treated with total mastectomy along with lipofilling. We also found no significant differences in the incidence of recurrence when segmental and total mastectomy with lipofilling were individually compared to the control group.

The only variable that significantly increased the risk of breast cancer recurrence with lipofilling was receipt of hormonal therapy. Although the cases were more likely to receive hormonal therapy, the cases and controls had similar hormonal receptor status. Eight of 805 patients with hormonal therapy had locoregional recurrence. Among them, the locoregional recurrence rate in the cases was approximately three times that of the controls. A hypothetical potential role of hormonal therapy in enhancing a tumorigenic microenvironment or impacting crosstalk between adipose-derived mesenchymal stem cells and breast cancer cells is unknown based on current scientific knowledge. Although lipoaspirate is a known reservoir for adipose-derived mesenchymal stem cells, adipose-derived mesenchymal stem cells are not tumorigenic per se, as they are not able to induce neoplastic transformation of normal mammary cells. However, it is not known whether adipose-derived mesenchymal stem cells can exacerbate tumorigenic behavior in breast cancer cells, theoretically creating an inflammatory microenvironment that sustains tumor growth and angiogenesis.[10] Interestingly, we also found that neither the total volume of fat injected nor the number of fat grafting sessions performed impacted locoregional recurrence. However, we found that larger grafts were required for the breasts with cancer than for the healthy breasts.

In assessment of our study, the degree to which the cases and controls were similar is an important consideration. Although there were some differences between cases and controls, including longer follow-up time, slightly older age, more stage 0 and I breast cancers, and more receipt of hormonal therapy among the cases, the cases and controls had similar hormonal receptor status, and the clinicopathologic differences tended to even the groups with respect to expected risk of locoregional recurrence. For instance, the higher stages of disease (higher risk of recurrence) and more chemotherapy (more aggressive therapy) administered in the control group were balanced against the longer follow-up time (higher risk of detecting recurrence) and more hormonal therapy (less aggressive therapy) in the case group.

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