Immediate breast reconstruction : patient information, regional variations and effects of radiotherapy

Abstract: The type of surgical treatment in breast cancer shows strong regional variation. The aim of studies I-III was to specifically investigate causes of the disparity in breast conservation and immediate breast reconstruction (IBR) rates in the six Swedish healthcare regions. All women who underwent any surgical intervention for primary breast cancer in Sweden in 2013 were included. Tumour and treatment data were retrieved from the Swedish National Breast Cancer Register, and socioeconomic background data from the Central Bureau of Statistics Sweden. Postal questionnaires regarding preoperative information and involvement in the preoperative decisionmaking process were sent to all mastectomy patients, with a response rate of 76.3%. Of 7735 women, 4604 (59.5%) had breast conservation and 3131 (40.5%) mastectomy, 267 of whom also received IBR. While tumour and patient characteristics predictably affected surgical treatment, they could not explain regional variations. Higher socioeconomic status resulted in a higher rate of IBR and breast conservation. Patient-reported preoperative information (OR 12.73, 95% Cl 6.03-26.89) and involvement in the decision-making process (OR 2.56, 95% Cl 1.14-5.76) remained strong independent predictors of IBR even after adjustment for socioeconomic factors. After implant-based IBR, primary expander devices are frequently exchanged for permanent silicone implants. The aim of study IV was to assess whether the timing of this exchange procedure in relation to the completion of post-mastectomy radiotherapy (PMRT) and other clinical factors affect surgical complications rates resulting in implant failure (primary outcome). All women previously treated with an IBR who underwent implant exchange and/or capsulectomy at Karolinska University Hospital between 2005 and 2015 were included. Detailed information was collected through individual medical chart review. The final cohort consisted of 475 breast cancer patients with 707 implant revision surgeries in 542 breasts, in which 33 cases of implant failure were observed. PMRT, smoking and diabetes were confirmed as risk factors, while time from completion of PMRT to revision surgery was not associated with the outcome. Additional risk factors were a previous axillary lymph node dissection and a history of a post-IBR infection. A common problem in implant-based IBR is the development of a capsular contracture secondary to PMRT. Study V evaluated gene expression patterns in biopsies from irradiated (n=13) and non-irradiated (n=12) capsular tissue harvested during implant exchange surgery in IBR patients, and gene expression levels were compared in order to identify the most differentially regulated genes in order to explore the underlying biology with the wider aim to generate knowledge enabling the development of therapeutic strategies. Radio-responsive genes were most often involved in inflammation immune response, and both innate and adaptive immune system responses were confirmed by immunohistochemistry on the protein level. There was a significant upregulation in CD20+ B-cell counts in irradiated biopsies, which was supported by gene expression analysis. However, the findings need to be confirmed in a larger study.