Breast Reconstruction and Neoadjuvant Radiotherapy — BRENAR  

Breast Cancer Clinical Trial

Official title: Breast Reconstruction and Neoadjuvant Therapy, a Changing Algorithm

Status Recruiting

Clinical Trial Summary

The purpose the BRENAR pilot study is to assess acute post-surgical complications following mastectomy and immediate breast reconstruction after neoadjuvant radiotherapy (NART). The investigators hypothesize that NART will avoid the negative effects of postmastectomy radiotherapy (PMRT) on the capsule of an implant, or on the skin and underlying tissue of an autologous flap, and would therefore lead to better cosmetic results, better quality of life and less complications compared to PMRT. If this hypothesis is confirmed, NART would allow more patients to undergo an immediate reconstruction resulting in superior cosmetic results and quality of life. Furthermore, the use of RT in a neoadjuvant setting could potentially result in a shorter overall loco-regional treatment time from diagnosis to receiving the last locoregional treatment. However, this pilot study will mainly assess whether or not the post-surgical complications of breast reconstruction with NART are acceptable. Further study to investigate long term quality of life and oncologic follow-up results will be conducted after this pilot study, if complication rates are acceptable.

Clinical Trial Description

Rationale: Treatment of patients with breast cancer requires a multimodality approach with often systemic therapy, radiotherapy (RT) and surgery. Postmastectomy radiotherapy (PMRT) reduces locoregional recurrences and improves survival, especially in patients with involved axillary nodes. However, PMRT is known to substantially increase the complication rate when combined with a breast reconstruction. Breast reconstructions can be performed within the same surgery as the mastectomy (i.e. immediate) or in a later stage where patients remain without a breast contour for several months to years before the reconstruction is completed (i.e. delayed). In the Netherlands, most patients are being withheld an immediate breast reconstruction if there is the slightest risk of PMRT, because PMRT in combination with immediate breast reconstruction is associated with a severe increase in postoperative complications, especially in case of an implant-based reconstruction: complication rates up to 40% have been reported, in comparison to less than 10% without PMRT. Short-term complications include infection and loss of implant, while long-term complications include pain, capsular contracture and fibrosis. Such complications have been shown to negatively affect quality of life, perceived body image and sexual well-being. Furthermore, PMRT after an immediate reconstruction is associated with impaired cosmetic results and lower patient satisfaction, even when no complications have occurred. If patients aim for an autologous reconstruction (i.e. use of own tissue), usually PMRT is performed first, followed by a delayed autologous reconstruction to avoid radiotherapy on the flap, thereby subjecting patients to a second major surgical procedure and a long period of living without a breast contour. The unsatisfying cosmetic results and high complication rate have led to controversy and a wide practice variation in reconstruction approaches that are being offered to this specific group of patients. Since immediate breast reconstructions have proven to yield better cosmetic outcomes, psychosocial results and reduced overall costs, solutions that would allow for an immediate breast reconstruction in combination with radiation therapy (RT), without an increase in complications, are highly needed. Previous studies in breast cancer patients indicated that neoadjuvant RT (NART) is a safe approach from an oncological perspective, and does not increase the overall post-operative complication rate. However, limited data are available on NART in combination with an immediate breast reconstruction, and no data are available on patient-reported cosmetic outcomes. Objective: The purpose of the pilot study is to assess acute post-surgical complications following mastectomy and immediate breast reconstruction after NART. The investigators hypothesize that NART will avoid the negative effects of PMRT on the capsule of an implant, or on the skin and underlying tissue of an autologous flap, and would therefore lead to better cosmetic results, better quality of life and less complications compared to PMRT. If this hypothesis is confirmed, NART would allow more patients to undergo an immediate reconstruction resulting in superior cosmetic results and quality of life. Furthermore, the use of RT in a neoadjuvant setting could potentially result in a shorter overall loco-regional treatment time from diagnosis to receiving the last locoregional treatment. However, this pilot study will mainly assess whether or not the post-surgical complications of breast reconstruction with NART are acceptable. Further study to investigate long term quality of life and oncologic follow-up results will be conducted after this pilot study, if complication rates are acceptable. Study design: The study will be conducted as a prospective multicenter single arm interventional pilot study. The primary endpoint is post-surgical complications at three months after the latest patient has received the final reconstructive surgery. Study population: Twenty breast cancer patients will be included after they have given informed consent. Patients are eligible if they have an indication for mastectomy and RT, and a wish for an immediate reconstruction, either implant-based or autologous, in MUMC, UMCU, Alexander Monro hospital and Amsterdam UMC. Intervention (if applicable): The intervention consists of NART followed by mastectomy with immediate reconstruction, where the standard treatment is mastectomy and PMRT, with an immediate or delayed reconstruction. Main study parameters/endpoints: Primary endpoint: Acute post-surgical complications at 3 months following mastectomy and immediate breast reconstruction after NART in the treatment of breast cancer. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Burden: Currently, in certain hospitals, the indication for RT is based upon the pathological nodal status of the sentinel or previously involved nodes, removed during mastectomy. Since patients in this study will receive NART, the indication for RT is not always clear prior to surgery. In those cases, an axillary staging procedure has to be performed prior to the breast surgery, to determine whether there is an indication for RT at all. This requires two separate surgical procedures, which is nowadays already common practice in several hospitals, to determine whether an immediate breast reconstruction is possible. Currently, for cT1-3N0 patients, it is known that about 25% has a positive axillary node after neoadjuvant chemotherapy and thus still requires PMRT; for patients with cT1-3N+ breast cancer, about 55-70% still have positive nodes after neoadjuvant chemotherapy requiring PMRT. Consequently, some patients that have given their informed consent for NART but will be excluded from this study if the sentinel node appears to be free of tumor cells. Another additional burden can be an additional biopsy of the tumor after neoadjuvant chemotherapy, to determine whether residual disease is present. If residual disease is present, there is also an indication for adjuvant systemic treatment in triple negative patients or her2- positive patients. Since a biopsy is not sufficiently accurate to determine pCR status, patients are excluded from the study if the biopsy does not contain tumors cells, since NART can influence the final pathological tumor status. Finally, from a patient's perspective, additional time is required for filling in questionnaires with regard to cosmetic results and quality of life (approximately 15-30 minutes). Risk Data from current pilot studies indicates that NART is at least as effective as PMRT with regard to oncologic safety. A risk that is associated with participation is the possibility of decreased vascularization of the skin (nipple) flap of the breast after a sparing mastectomy leading to early complications, especially in the implant group. However, it is anticipated that this risk of necrosis and loss of tissue expander/implant is low, since previous pilot studies showed that overall short and long-term complications were similar between PMRT and NART. Benefit and group relatedness: NART will allow patients to always receive an immediate breast reconstruction (both implant-based and autologous), even is RT is indicated. It is hypothesized that this will result in a better QoL and cosmetic outcome. Finally total treatment time will be shorter with NART. ;

Related Conditions & MeSH terms

• Breast Cancer

• NCT number: NCT05216900
• Study type: Interventional
• Source: UMC Utrecht
• Contact: Wies Maarse, PhD, MD
• Phone: +31626598153
• Email: w.maarse@umcutrecht.nl
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2023
• Completion date: December 4, 2026