Oncological safety and health-related quality of life after reconstructive breast cancer surgery

Abstract: The main aim of this thesis was to gain knowledge about the oncological safety of nipple- sparing mastectomy (NSM) with immediate implant-based reconstruction and delayed Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction. In this context, we also considered the impact of discrepancies in socioeconomic status (SES) and comorbidity. Finally, we investigated the effects of radiotherapy (RT) on implant-based immediate breast reconstruction (IBR) measuring failure rates, number of unplanned reoperations and patient- reported outcomes (PROs). In study I, we studied the local recurrence rates as well as disease-free, overall and breast cancer-specific survival (BCSS) after NSM and IBR compared with a matched control group of patients undergoing conventional mastectomy. Matching variables were tumour stage, age, and year of mastectomy. A total of 69 NSM cases and 206 conventional mastectomies operated between 2000 and 2012 were included. While no local recurrence occurred in the study group, seven were observed in the control group (P=0.197). Survival rates did not differ significantly between groups. In study II, we aimed to estimate the risk of breast cancer recurrence after DIEP flap reconstruction compared with patients treated with mastectomy without any delayed reconstruction. A total of 254 DIEP cases operated between 1999 and 2013 and 729 control cases were included. Matching variables were age, tumour stage, neoadjuvant therapy, and year of DIEP flap reconstruction. The primary endpoint, 5-year BCSS, was significantly higher in the DIEP group, which did not persist after adjustment for tumour and patient characteristics and treatment. Overall survival (OS) remained significantly lower in the control group despite adjustment. We therefore aimed to address the observed survival differences by further adjusting for SES) and comorbidity in study III. Data for the estimation of the Charlson Comorbidity Index and SES were obtained from Swedish national registers. In the DIEP group, it was more common to continue education after primary school, to have a higher income, and to be in a partnership. Women in the DIEP group were also significantly healthier than women in the control group. After adjustment for SES and comorbidity, however, OS was still significantly better in the DIEP group than the control group, which is potentially due to unaccounted confounders such as body mass index (BMI), smoking and selection bias inherent to the reconstructive decision-making process. In study IV we re-evaluated a previously reported large homogenous IBR cohort with regards to surgical results and PROs. All women undergoing a therapeutic mastectomy with implant- based IBR at Stockholm’s main four hospitals between 2007 and 2011 were included (N=754 IBRs). Of those, 386 had not been irradiated, 64 were irradiated prior to IBR, and 304 after IBR. The primary endpoint was IBR failure, defined as implant removal due to any cause, with or without a conversion to an autologous reconstruction. BREAST-Q questionnaires were sent out to all patients alive with no record of implant removal. Between-group comparisons and longitudinal within-groups differences were assessed. IBR failure occurred in 128 cases (17%) with the higher proportion in the postoperative and prior RT groups, 24.3% and 31.3% respectively, (P<0.001). Independent risk factors for IBR failure were irradiation, age > 50 at time of IBR, BMI ≥ 25, and postoperative surgical complication. With a response rate of 72.2%, women with prior RT scored significantly lower than those without RT on most subscales, while women with postoperative RT reported significantly lower scores on physical well-being only. Among responders, psychosocial well-being had increased over the past eight years in the postoperative RT group, and satisfaction with breasts and with overall outcome had significantly decreased in the no RT group. Of note, women with implant failure after irradiation were not included in PROs analysis since the specific questions are not applicable to someone who has either had her implant removed or converted to an autologous reconstruction. Thereby, PROs results may have been affected by selection bias.