We read with great interest the article by Thomas et al. on delivering antiestrogen with autologous adipose tissue.1 Autologous tissues have been explored as drug carriers for a long period because of their good histocompatibility and accessibility. Compared with other cells, adipose cells, with a huge storage capacity, can be obtained harmlessly and efficiently with syringe lipoaspiration techniques. Moreover, large lipid droplets in adipose cells give them natural lipophilicity to load fat-soluble drugs well. Some researchers had attempted to use adipose cells in breast cancer hormone therapy.2,3 However, there are still some flaws with reliability and effectiveness of this technique.
First, release of antiestrogen from adipose tissue is not stable and is insufficient for therapy. Unlike those cultivated in vitro, without good vascularization, most cells do not survive over 24 hours. In the long term, the absorption rate of grafted adipose tissue could rise to as high as 25 to 80 percent.4 During necrotic disintegration, lipid droplets loading drugs will be excreted largely and rapidly, which means drug concentration varies depending on the condition of adipocyte necrosis. As this article showed, when cultured with fulvestrant, adipose cells did not demonstrate obvious reduction in proliferation and viability. However, another study3 showed tamoxifen, a classic antiestrogen, inhibited the proliferation, viability, and differentiation ability of adipose-derived stem cells definitely; these constitute a small proportion of adipose tissue but are essential for regeneration of adipose cells when the grafted one comes into contact with necrotic tissue. This implies that fulvestrant did not influence the quantity of adipose cells at the early time point but would reduce the retention and survival rates of adipose tissue and impact the final result of breast reconstruction.
Second, local therapy might not help prevent distant metastasis and improve clinical outcome. As the classic Halstedian paradigm, breast cancer is a localized disease and spreads in a centrifugal manner to distant tissue along fascial planes or lymphatics. However, for individual trials, a decrease of local recurrence did not translate into survival differences,5 which suggests that a Fisherian paradigm presupposing that breast cancer is a systemic disease initially may make sense and that the solo use of antiestrogen in local sites does not benefit patients with distant micrometastasis, causing death of patients. Furthermore, in the article by Thomas et al., proliferation and viability are eliminated by fulvestrant released by adipose tissues, but characteristics such as invasiveness were not measured, the increase of which leads to a worse clinical outcome. In addition, the peak release time of fulvestrant is the first several days after grafting. During that period, without vascularization, the major way of maintaining the nutrition of adipose cells is infiltration from surrounding tissue fluid, with a very limited distance of 150 to 200 μm. The released drugs only contact a restricted range of tissue and have a limited prohibition on residual cancer sites and local recurrence.
Despite technical difficulties in this practice, the efforts of Thomas et al. have verified crucial issues such as oncologic safety and technical feasibility. We thank Thomas et al. for their important efforts. We anticipate further progress such as transgenic adipose cells to generate drug and new prosthesis to load antiestrogen.
The authors have no financial interest to declare in relation to the content of this communication. No funding was received for this work.
Yiye Ouyang, M.D.Chengcheng Li, M.D.Chunjun Liu, M.D.Plastic Surgery HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing, People’s Republic of China
1. Thomas S, Chen S, Sbitany H, et al. Autologous fat grafting as a novel antiestrogen vehicle for the treatment of breast cancer. Plast Reconstr Surg. 2017;140:537544.
2. Munster PN, Chen S, Thomas S, et al. Abstract P4-16-01: A novel approach to breast cancer prevention: Exploiting autologous fat grafting for the local delivery of cancer therapeutics. Cancer Res. 2013;73(Suppl):P41601.
3. Valentin J, Tsuji W, Chung C, et al. Abstract 128: Developing tumor-suppressing autologous fat grafts for breast cancer survivors. Plast Reconstr Surg. 2014;133(Suppl):144145.
4. Kølle SF, Fischer-Nielsen A, Mathiasen AB, et al. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: A randomised placebo-controlled trial. Lancet 2013;382:11131120.
5. Benson JR, Teo KA. Breast cancer local therapy: What is its effect on mortality? World J Surg. 2012;36:14601474.