Oncological Recurrence after Autologous Fat Grafting in Breast Reconstruction; Critical appraisal of the current literature on basic science and clinical studies
Abstract
Background:
The use of Autologous Fat Grafting (AFG) in surgical procedures of the female breast has gained enormous international interest over the last decade with indications ranging from aesthetic augmentation to the treatment of post-mastectomy-pain-syndromes and breast-reconstructions. One of the most important unanswered questions remains that of oncological-safety, with an almost equal sum of clinical- and basic-science-studies suggesting oncological-safety and an increased risk of oncological recurrence respectively. In this paper the authors aim to provide a comprehensive overview of the overwhelming data currently available on the subject of oncological-safety after AFG for (breast) reconstructive purposes.
Method:
An extensive literature search was performed using the following databases; PubMed, Embase.com, Wiley/Cochrane Library and Web of Science. Original studies reporting on AFG for (breast) reconstructive purposes were included and a tabulated overview of data regarding oncological-safety from either a clinical- or basic-science point-of-view are provided.
Results
Thirty-five and twenty-one basic-science- and clinical-studies reported on oncological safety respectively. Thirty-one basic-science-studies described the carcinogenic effects of AFG with most reporting the effects of adipocyte-derived-stemcells in stimulating growth, migration, neo-vascularisation, self-renewal or metastatic-capabilities of different breast-cancer-cell-lines through various pathways. A meta-analysis of clinical-studies on oncological-safety after cancer treatment and breast reconstruction with AFG in a total of 2953 patients reported a locoregional-recurrence-rate of 2.5% and a distant-recurrence-rate of 2.0% with no difference between mastectomy and breast-conserving-therapy patients (p=0.69). However, a significant higher number of locoregional recurrences compared to a control group were found in two sub-cohorts of intra-epithelial neoplasms.
Conclusion
It is clear that more scientific data from both basic science studies using clinical breast cancer samples with representable ASC concentrations as well as clinical studies, preferably RCT’s, with a clear distinction between breast cancer types and the recurrence risk after breast-conserving therapy are needed in order to make clear assumptions about oncological safety of AFG.
Keywords
Full Text:
Subscribers OnlyReferences
References:
F. N. Fettransplantation. Chir Kongr Verhandl Dsch Gesellch Chir. 1893;22(66).
Report on autologous fat transplantation. ASPRS Ad-Hoc Committee on New Procedures, September 30, 1987. Plastic surgical nursing : official journal of the American Society of Plastic and Reconstructive Surgical Nurses. 1987;7(4):140-141.
SOCIETE FRANCAISE DE CHIRURGIE PLASTIQUE RECONSTRUCTRICE ET ESTHETIQUE (SOF.CPRE). Transfert graisseux pour la correction des s'equelles du traitement conservateur du cancer du sein. Plasticiens.fr. 2015.
Web page: http://www.associationofbreastsurgery.org.uk/media/4605/lipomodelling_guidelines_for_breast_surgery.pdf. Date last accessed 20 Aug 2016.
Fatah. F LM, Martin L. Lipomodelling guidelines for breast surgery. Joint Guidelines from ABS, BAPRAS and BAAPS. 2012.
International Society of Plastic Aesthetic Surgery. ISAPS International Survey on Aesthetic/Cosmetic Procedures performed in 2013. Web page: http://www.isaps.org/Media/Default/global-statistics/2014% 20ISAPS%20Global%20Stat%20Results.pdf. Date last accessed 20 Aug 2016.
Coleman SR, Saboeiro AP. Fat grafting to the breast revisited: safety and efficacy. Plastic and reconstructive surgery. 2007;119(3):775-785; discussion 786-777.
Zhong T, McCarthy CM, Price AN, Pusic AL. Evidence-based medicine: breast reconstruction. Plastic and reconstructive surgery. 2013;132(6):1658-1669.
Missana MC, Laurent I, Barreau L, Balleyguier C. Autologous fat transfer in reconstructive breast surgery: indications, technique and results. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2007;33(6):685-690.
Tsoi B, Ziolkowski NI, Thoma A, Campbell K, O'Reilly D, Goeree R. Systematic review on the patient-reported outcomes of tissue-expander/implant vs autologous abdominal tissue breast reconstruction in postmastectomy breast cancer patients. Journal of the American College of Surgeons. 2014;218(5):1038-1048.
Khouri RK, Eisenmann-Klein M, Cardoso E, et al. Brava and autologous fat transfer is a safe and effective breast augmentation alternative: results of a 6-year, 81-patient, prospective multicenter study. Plastic and reconstructive surgery. 2012;129(5):1173-1187.
Khouri RK, Khouri RK, Jr., Rigotti G, et al. Aesthetic applications of Brava-assisted megavolume fat grafting to the breasts: a 9-year, 476-patient, multicenter experience. Plastic and reconstructive surgery. 2014;133(4):796-807; discussion 808-799.
Gutowski KA, Force AFGT. Current applications and safety of autologous fat grafts: a report of the ASPS fat graft task force. Plastic and reconstructive surgery. 2009;124(1):272-280.
Smit JM, Tielemans HJ, de Vries B, Tuinder SM. Recurrence of invasive ductal breast carcinoma 10 months after autologous fat grafting. Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2014;67(5):e127-128.
Chaput B, Foucras L, Le Guellec S, Grolleau JL, Garrido I. Recurrence of an invasive ductal breast carcinoma 4 months after autologous fat grafting. Plastic and reconstructive surgery. 2013;131(1):123e-124e.
Petit JY, Botteri E, Lohsiriwat V, et al. Locoregional recurrence risk after lipofilling in breast cancer patients. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2012;23(3):582-588.
Petit JY, Rietjens M, Botteri E, et al. Evaluation of fat grafting safety in patients with intraepithelial neoplasia: a matched-cohort study. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2013;24(6):1479-1484.
Krastev TK, Jonasse Y, Kon M. Oncological safety of autologous lipoaspirate grafting in breast cancer patients: a systematic review. Annals of surgical oncology. 2013;20(1):111-119.
Chan CW, McCulley SJ, Macmillan RD. Autologous fat transfer--a review of the literature with a focus on breast cancer surgery. Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2008;61(12):1438-1448.
Fraser JK, Hedrick MH, Cohen SR. Oncologic risks of autologous fat grafting to the breast. Aesthetic surgery journal / the American Society for Aesthetic Plastic surgery. 2011;31(1):68-75.
Krumboeck A, Giovanoli P, Plock JA. Fat grafting and stem cell enhanced fat grafting to the breast under oncological aspects--recommendations for patient selection. Breast. 2013;22(5):579-584.
Claro F, Jr., Figueiredo JC, Zampar AG, Pinto-Neto AM. Applicability and safety of autologous fat for reconstruction of the breast. The British journal of surgery. 2012;99(6):768-780.
Groen JW, Negenborn VL, Twisk DJ, et al. Autologous fat grafting in onco-plastic breast reconstruction: A systematic review on oncological and radiological safety, complications, volume retention and patient/surgeon satisfaction. Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2016;69(6):742-764.
Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. The New England journal of medicine. 2002;347(16):1233-1241.
Kroll SS, Schusterman MA, Tadjalli HE, Singletary SE, Ames FC. Risk of recurrence after treatment of early breast cancer with skin-sparing mastectomy. Annals of surgical oncology. 1997;4(3):193-197.
Petit JY, Gentilini O, Rotmensz N, et al. Oncological results of immediate breast reconstruction: long term follow-up of a large series at a single institution. Breast cancer research and treatment. 2008;112(3):545-549.
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. The New England journal of medicine. 2002;347(16):1227-1232.
Groen JW, Negenborn VL, Twisk JW, Ket JC, Mullender MG, Smit JM. Autologous Fat Grafting in Cosmetic Breast Augmentation: A Systematic Review on Radiological Safety, Complications, Volume Retention, and Patient/Surgeon Satisfaction. Aesthetic surgery journal / the American Society for Aesthetic Plastic surgery. 2016.
Eterno V, Zambelli A, Pavesi L, et al. Adipose-derived Mesenchymal Stem Cells (ASCs) may favour breast cancer recurrence via HGF/c-Met signaling. Oncotarget. 2014;5(3):613-633.
Kuhbier JW, Bucan V, Reimers K, et al. Observed changes in the morphology and phenotype of breast cancer cells in direct co-culture with adipose-derived stem cells. Plastic and reconstructive surgery. 2014;134(3):414-423.
Rowan BG, Gimble JM, Sheng M, et al. Human adipose tissue-derived stromal/stem cells promote migration and early metastasis of triple negative breast cancer xenografts. PloS one. 2014;9(2):e89595.
Ke CC, Liu RS, Suetsugu A, et al. In vivo fluorescence imaging reveals the promotion of mammary tumorigenesis by mesenchymal stromal cells. PloS one. 2013;8(7):e69658.
Zimmerlin L, Donnenberg AD, Rubin JP, Basse P, Landreneau RJ, Donnenberg VS. Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates. Tissue engineering. Part A. 2011;17(1-2):93-106.
Orecchioni S, Gregato G, Martin-Padura I, et al. Complementary populations of human adipose CD34+ progenitor cells promote growth, angiogenesis, and metastasis of breast cancer. Cancer research. 2013;73(19):5880-5891.
Bertolini F. Contribution of endothelial precursors of adipose tissue to breast cancer: progression-link with fat graft for reconstructive surgery. Annales d'endocrinologie. 2013;74(2):106-107.
Gehmert S, Prantl L, Vykoukal J, Alt E, Song YH. Breast cancer cells attract the migration of adipose tissue-derived stem cells via the PDGF-BB/PDGFR-beta signaling pathway. Biochemical and biophysical research communications. 2010;398(3):601-605.
Chandler EM, Seo BR, Califano JP, et al. Implanted adipose progenitor cells as physicochemical regulators of breast cancer. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(25):9786-9791.
Bochet L, Lehuede C, Dauvillier S, et al. Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer. Cancer research. 2013;73(18):5657-5668.
Hass R, Otte A. Mesenchymal stem cells as all-round supporters in a normal and neoplastic microenvironment. Cell communication and signaling : CCS. 2012;10(1):26.
Zhang Y, Daquinag AC, Amaya-Manzanares F, Sirin O, Tseng C, Kolonin MG. Stromal progenitor cells from endogenous adipose tissue contribute to pericytes and adipocytes that populate the tumor microenvironment. Cancer research. 2012;72(20):5198-5208.
Mandel K, Yang Y, Schambach A, Glage S, Otte A, Hass R. Mesenchymal stem cells directly interact with breast cancer cells and promote tumor cell growth in vitro and in vivo. Stem cells and development. 2013;22(23):3114-3127.
Devarajan E, Song YH, Krishnappa S, Alt E. Epithelial-mesenchymal transition in breast cancer lines is mediated through PDGF-D released by tissue-resident stem cells. International journal of cancer. 2012;131(5):1023-1031.
Kucerova L, Kovacovicova M, Polak S, et al. Interaction of human adipose tissue-derived mesenchymal stromal cells with breast cancer cells. Neoplasma. 2011;58(5):361-370.
Burger JA, Kipps TJ. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood. 2006;107(5):1761-1767.
Kang H, Watkins G, Parr C, Douglas-Jones A, Mansel RE, Jiang WG. Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer. Breast cancer research : BCR. 2005;7(4):R402-410.
Krohn A, Song YH, Muehlberg F, Droll L, Beckmann C, Alt E. CXCR4 receptor positive spheroid forming cells are responsible for tumor invasion in vitro. Cancer letters. 2009;280(1):65-71.
Rhodes LV, Antoon JW, Muir SE, Elliott S, Beckman BS, Burow ME. Effects of human mesenchymal stem cells on ER-positive human breast carcinoma cells mediated through ER-SDF-1/CXCR4 crosstalk. Molecular cancer. 2010;9:295.
Rhodes LV, Short SP, Neel NF, et al. Cytokine receptor CXCR4 mediates estrogen-independent tumorigenesis, metastasis, and resistance to endocrine therapy in human breast cancer. Cancer research. 2011;71(2):603-613.
Lu X, Kang Y. Chemokine (C-C motif) ligand 2 engages CCR2+ stromal cells of monocytic origin to promote breast cancer metastasis to lung and bone. The Journal of biological chemistry. 2009;284(42):29087-29096.
Yoshimura T, Howard OM, Ito T, et al. Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells. PloS one. 2013;8(3):e58791.
Yaal-Hahoshen N, Shina S, Leider-Trejo L, et al. The chemokine CCL5 as a potential prognostic factor predicting disease progression in stage II breast cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006;12(15):4474-4480.
Pinilla S, Alt E, Abdul Khalek FJ, et al. Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion. Cancer letters. 2009;284(1):80-85.
Svensson S, Abrahamsson A, Rodriguez GV, et al. CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2015;21(16):3794-3805.
Kamat P, Schweizer R, Kaenel P, et al. Human Adipose-Derived Mesenchymal Stromal Cells May Promote Breast Cancer Progression and Metastatic Spread. Plastic and reconstructive surgery. 2015;136(1):76-84.
Welte G, Alt E, Devarajan E, Krishnappa S, Jotzu C, Song YH. Interleukin-8 derived from local tissue-resident stromal cells promotes tumor cell invasion. Molecular carcinogenesis. 2012;51(11):861-868.
Ritter A, Friemel A, Fornoff F, et al. Characterization of adipose-derived stem cells from subcutaneous and visceral adipose tissues and their function in breast cancer cells. Oncotarget. 2015;6(33):34475-34493.
Zimmerlin L, Park TS, Zambidis ET, Donnenberg VS, Donnenberg AD. Mesenchymal stem cell secretome and regenerative therapy after cancer. Biochimie. 2013;95(12):2235-2245.
Razmkhah M, Jaberipour M, Erfani N, Habibagahi M, Talei AR, Ghaderi A. Adipose derived stem cells (ASCs) isolated from breast cancer tissue express IL-4, IL-10 and TGF-beta1 and upregulate expression of regulatory molecules on T cells: do they protect breast cancer cells from the immune response? Cellular immunology. 2011;266(2):116-122.
Yang ZZ, Novak AJ, Ziesmer SC, Witzig TE, Ansell SM. CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25 T cells. Blood. 2007;110(7):2537-2544.
Wang T, Gilkes DM, Takano N, et al. Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(31):E3234-3242.
Nalwoga H, Ahmed L, Arnes JB, Wabinga H, Akslen LA. Strong Expression of Hypoxia-Inducible Factor-1alpha (HIF-1alpha) Is Associated with Axl Expression and Features of Aggressive Tumors in African Breast Cancer. PloS one. 2016;11(1):e0146823.
Walter M, Liang S, Ghosh S, Hornsby PJ, Li R. Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells. Oncogene. 2009;28(30):2745-2755.
Rubio D, Garcia-Castro J, Martin MC, et al. Spontaneous human adult stem cell transformation. Cancer research. 2005;65(8):3035-3039.
Qiao L, Xu ZL, Zhao TJ, Ye LH, Zhang XD. Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signalling. Cancer letters. 2008;269(1):67-77.
Ryu H, Oh JE, Rhee KJ, et al. Adipose tissue-derived
mesenchymal stem cells cultured at high density express IFN-beta and suppress the growth of MCF-7 human breast cancer cells. Cancer letters. 2014;352(2):220-227.
Sun B, Roh KH, Park JR, et al. Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy. 2009;11(3):289-298, 281 p following 298.
Zhu Y, Sun Z, Han Q, et al. Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia. 2009;23(5):925-933.
Perez-Cano R, Vranckx JJ, Lasso JM, et al. Prospective trial of adipose-derived regenerative cell (ADRC)-enriched fat grafting for partial mastectomy defects: the RESTORE-2 trial. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2012;38(5):382-389.
Botteri E, Bagnardi V, Rotmensz N, et al. Analysis of local and regional recurrences in breast cancer after conservative surgery. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2010;21(4):723-728.
Pierrefeu-Lagrange AC, Delay E, Guerin N, Chekaroua K, Delaporte T. [Radiological evaluation of breasts reconstructed with lipomodeling]. Annales de chirurgie plastique et esthetique. 2006;51(1):18-28.
Delay E, Gosset J, Toussoun G, Delaporte T, Delbaere M. [Efficacy of lipomodelling for the management of sequelae of breast cancer conservative treatment]. Annales de chirurgie plastique et esthetique. 2008;53(2):153-168.
Delay E, Garson S, Tousson G, Sinna R. Fat injection to the breast: technique, results, and indications based on 880 procedures over 10 years. Aesthetic surgery journal / the American Society for Aesthetic Plastic surgery. 2009;29(5):360-376.
Rigotti G, Marchi A, Stringhini P, et al. Determining the oncological risk of autologous lipoaspirate grafting for post-mastectomy breast reconstruction. Aesthetic Plast Surg. 2010;34(4):475-480.
Rietjens M, De Lorenzi F, Rossetto F, et al. Safety of fat grafting in secondary breast reconstruction after cancer. Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2011;64(4):477-483.
Petit JY, Lohsiriwat V, Clough KB, et al. The oncologic outcome and immediate surgical complications of lipofilling in breast cancer patients: a multicenter study--Milan-Paris-Lyon experience of 646 lipofilling procedures. Plastic and reconstructive surgery. 2011;128(2):341-346.
Sarfati I, Ihrai T, Kaufman G, Nos C, Clough KB. Adipose-tissue grafting to the post-mastectomy irradiated chest wall: preparing the ground for implant reconstruction. Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2011;64(9):1161-1166.
Costantini M, Cipriani A, Belli P, et al. Radiological findings in mammary autologous fat injections: a multi-technique evaluation. Clinical radiology. 2013;68(1):27-33.
Seth AK, Hirsch EM, Kim JY, Fine NA. Long-term outcomes following fat grafting in prosthetic breast reconstruction: a comparative analysis. Plastic and reconstructive surgery. 2012;130(5):984-990.
Sarfati I, Ihrai T, Duvernay A, Nos C, Clough K. [Autologous fat grafting to the postmastectomy irradiated chest wall prior to breast implant reconstruction: a series of 68 patients]. Annales de chirurgie plastique et esthetique. 2013;58(1):35-40.
Doren EL, Parikh RP, Laronga C, et al. Sequelae of fat grafting postmastectomy: an algorithm for management of fat necrosis. Eplasty. 2012;12:e53.
Riggio E, Bordoni D, Nava MB. Oncologic surveillance of breast cancer patients after lipofilling. Aesthetic Plast Surg. 2013;37(4):728-735.
Ihrai T, Georgiou C, Machiavello JC, et al. Autologous fat grafting and breast cancer recurrences: retrospective analysis of a series of 100 procedures in 64 patients. Journal of plastic surgery and hand surgery. 2013;47(4):273-275.
Longo B, Laporta R, Sorotos M, Pagnoni M, Gentilucci M, Santanelli di Pompeo F. Total Breast Reconstruction Using Autologous Fat Grafting Following Nipple-Sparing Mastectomy in Irradiated and Non-irradiated Patients. Aesthetic Plast Surg. 2014;38(6):1101-1108.
Kim HY, Jung BK, Lew DH, Lee DW. Autologous Fat Graft in the Reconstructed Breast: Fat Absorption Rate and Safety based on Sonographic Identification. Arch Plast Surg. 2014;41(6):740-747.
Semprini G, Cattin F, Zanin C, et al. About locoregional recurrence risk after lipofilling in breast cancer patients: our experience. Minerva Chir. 2014;69(2):91-96.
Molto Garcia R, Gonzalez Alonso V, Villaverde Domenech ME. Fat grafting in immediate breast reconstruction. Avoiding breast sequelae. Breast cancer. 2014.
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(2):159-165.
Charvet HJ, Orbay H, Wong MS, Sahar DE. The Oncologic Safety of Breast Fat Grafting and Contradictions Between Basic Science and Clinical Studies: A Systematic Review of the Recent Literature. Annals of plastic surgery. 2015;75(4):471-479.
Aust L, Devlin B, Foster SJ, et al. Yield of human adipose-derived adult stem cells from liposuction aspirates. Cytotherapy. 2004;6(1):7-14.
Oedayrajsingh-Varma MJ, van Ham SM, Knippenberg M, et al. Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure. Cytotherapy. 2006;8(2):166-177.
Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K. Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthetic Plast Surg. 2008;32(1):48-55; discussion 56-47.
Yoshimura K, Shigeura T, Matsumoto D, et al. Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates. Journal of cellular physiology. 2006;208(1):64-76.
Gale KL, Rakha EA, Ball G, Tan VK, McCulley SJ, Macmillan RD. A case-controlled study of the oncologic safety of fat grafting. Plastic and reconstructive surgery. 2015;135(5):1263-1275.
Wilkinson JB, Vicini FA, Shah C, et al. Twenty-year outcomes after breast-conserving surgery and definitive radiotherapy for mammographically detected ductal carcinoma in situ. Annals of surgical oncology. 2012;19(12):3785-3791.
Fertsch S HD, Munder DB. Risk score and factors for breast cancer patients planning to undergo lipofilling after Deep Inferior Epigastric Perforator (DIEP)-flap reconstruction. European Breast Cancer Conference (EBBC) March 2016, Amsterdam. 2016.
Krastev TK. Breast Reconstruction With External Pre-expansion and Autologous Fat Transfer Versus Standard Therapy (BREAST) trial, registered at https://clinicaltrials.gov/show/NCT023397792015
DOI: http://dx.doi.org/10.18103/imr.v3i2.359
Refbacks
- There are currently no refbacks.