Preoperative Radiation Therapy and Immediate Breast Reconstruction

The PRADAIIBE study is a multicentric phase III randomized controlled trial, investigating the effects of radiation therapy timing on breast reconstruction results in breast cancer patients. This study will recruit adult female breast cancer patients from the Belgian population, who have an indication for mastectomy, Post-Mastectomy Radiation Therapy (PMRT), and also have a wish for breast reconstruction. After informed consent is signed, patients will be screened, and included in the study if all eligibility criteria are met. If they are not eligible for participation or choose to withdraw after the ICF was signed, they will be registered as a 'screen failure'. After study inclusion, baseline assessments take place, this includes two questionnaires, one focussed on patient's satisfaction with their own breasts (BREAST-Q v2, BQ-score), the other one focussed on their quality of life perception (EQ-5D-5L VAS-score and Index-score). Next, four photographs of the exposed breast area will be taken. These photographs will later be assessed by an expert panel (AIS-TAS). Eligible participants are randomized using the central eCRF randomization tool (Castor EDC). Randomisation is stratified on study site and a variable block size will be used. Resulting in random assignment to one of the following treatment arms: * Control (SoC) treatment arm: Mastectomy followed by PMRT and delayed (or immediate) breast reconstruction. * Experimental treatment arm: preoperative radiation therapy (preop-RT) followed by mastectomy and immediate breast reconstruction. Those assigned to the control group will follow the standard of care (SoC) treatment consisting of oncological surgery (within 6 weeks of randomisation or end of preop chemotherapy) followed by radiation therapy (PMRT) within 6-12 weeks. The breast reconstruction surgery will take place either at the same time (e.g. tissue expander implantation) as the oncological surgery, or at a delayed moment (usually a 6-12 months delay). Patients assigned to the intervention group will receive preop-RT (within 6 weeks of randomisation or end of preop chemotherapy), and after an interval of 2-6 weeks mastectomy combined with immediate breast reconstruction will be performed. The radiation therapy will be administered according to the same principles as PMRT/Whole Breast Radiation Therapy (WBRT). This change to preoperative timing of the radiation therapy allows for immediate breast reconstruction without irradiation of the reconstructed breast. In the unexpected event of tumour downstaging due to preoperative treatment, changing the indication from mastectomy to breast conserving surgery (BCS), while the patient has already been included, it is allowed within the study protocol to perform BCS. In this case the patient should receive the treatment and surgery which is in their best interest. The same follow-up will be provided. In statistical analysis results from such patients will be handled according to the inter-current events (ICE) strategies defined in the SAP. However, such downstaging is not expected from preop-RT at such a short treatment interval of 2-6 weeks. Systemic therapy will be administered per standard of care, according to the discretion of the treating medical oncologist. Systemic therapy details will be registered in the eCRF, but it is not considered as part of the study treatments, and will not be manipulated within this trial. After the treatment period is finished (last study treatment) follow-up will take place at 3 months, 1 year, 2 years, 5 years and 10 years. In the control group, patients undergoing delayed breast reconstruction will be invited to an intermediate follow up visit (IMFU) visit at 3 months after conclusion of radiation therapy. The reason for this IMFU visit is to capture the outcomes of interest in the interval between mastectomy and breast reconstruction, as well as provide continued study follow-up during this long treatment interval of +/- 6-12 months. During each follow-up visit the BREAST-Q and EQ-5D-5L questionnaires will be assessed, photographs will be taken and evaluated at a later (expert panel using the AIS-tool), adverse events will be elicited, pathologic response assessed, treatment milestones are recorded (treatment duration) and oncological recurrence is assessed from the +1 year visit onwards according to the events and outcomes described in the DATECAN 2015 initiative.