Autologous fat transplantation to the female breast after surgery and radiotherapy assessment of patient-reported outcomes, radiology and gene expression patterns

Abstract: Autologous fat transplantation (AFT) is commonly used as a complementary method to enhance breast appearance after breast surgery, radiotherapy and breast reconstruction. Some of the indications for AFT to the breast are contour irregularities, volume deficits, chronic wounds, soft tissue indurations and scarring. Although AFT is well established with the primary aim with AFT is to enhance the patient’s satisfaction, research on patient perceptions is sparse. In the 1980s the American Society of Plastic Surgeons (former American Society of Plastic and Reconstructive Surgeons) expressed the concern that AFT could lead to false- positive radiological findings that subsequently would lead to excessive examinations. In 2009 they requested more studies on AFT to breast cancer patients. Apart from using autologous fat as a filler and to soften the breast tissue, AFT can be used to mitigate radiation-induced fibrosis and dermatitis. The effect of AFT on radiation-damaged tissue is well described clinically, but the biological processes behind the effects are still unknown. These issues were also studied in the present research. A retrospective study (I) was carried out on 43 patients using a study-specific questionnaire to assess their perceptions of the results of AFT. Post-operative complications were also recorded. The patients reported overall good results and only one minor complication was found in all patients. In a prospective case-series (II) patient-reported outcomes were assessed in 48 patients using a study-specific questionnaire and the 36-Item Short Form Health Survey (SF-36), before, and up to two years after AFT. Sixteen of the 20 items in the questionnaire were significantly improved two years post-operatively, including pain, scars, appearance and softness of the breast, as well as inclination to perform physical activities in public areas. The scores obtained with SF-36 concerning health related quality of life did not change after AFT, and did not differ from a Swedish reference population. In the third study (III), 44 patients underwent mammography and ultrasound before and one year after AFT. Assessment was carried out by experienced radiologists. No difference in the overall assessment (BI-RADS score 2) could be seen. AFT was found to significantly increase the number of breasts with oil cysts, where the breasts with oil cysts had been transplanted with larger volumes of fat. Finally, gene expression in adipose tissue was investigated with microarray technique and Hallmark gene set enrichment analysis (IV). Biopsies were taken from the adipose tissue of the irradiated breast and the contralateral non-irradiated breast of ten women before AFT. Biopsies were also taken bilaterally one year after AFT of the irradiated breast. Among the 3000 most differentially expressed genes comparing irradiated and non-irradiated biopsies before AFT, 45 enriched pathways were found. After AFT to the irradiated breast, 575 of the 3000 previously differentially expressed genes were reversed in the irradiated and AFT treated adipose tissue, and thus affected by AFT. Among these 575 genes, 13 pathways were identified, all of them also found in the pre-operative analysis. The leading canonical pathways in the two analyses were interferon gamma response, hypoxia and epithelial mesenchymal transition. The conclusions drawn from these studies are that AFT was perceived as a good complementary method of treatment by the patients, who experienced improvements in several aspects, and that AFT has no or little negative effects on post-operative radiological assessment. Furthermore, may AFT reverse differential gene expression in genes involved in inflammation, hypoxia and fibrosis that could have been caused by radiotherapy.