Breast cancers requiring mastectomy and radiotherapy, and suitable for immediate autologous microvascular breast reconstruction. Cancer
Conditions
Interventions
This is a multicentre, randomised (1:1) controlled trial, comparing pre-operative radiation to post-operative radiation in locally advanced breast cancers requiring mastectomy and autologous reconstru
Sponsors
Imperial College London
Eligibility
Sex/Gender
Female
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Women >= 18 years of age, diagnosed with biopsy-proven, locally advanced breast cancer defined by any of the following (derived from diagnostic imaging) based on the latest guidance from the American Joint Committee on Cancer Staging (2017): 1.1. Tumour (T) stage T3 or T4 and any Nodal (N) stage 1.2. Any T stage, N2 or N3 disease 1.3. T2 and/or N1 disease with additional risk factors for local recurrence, including: 1.3.1. Medial tumour thought to benefit from internal mammary radiation, and/or 1.3.2. Chemoresistant disease (if ER negative and/ or HER-2 positive) 2. In addition: 2.1. Patients must be suitable for autologous reconstruction using microsurgical techniques, including any of the following techniques: 2.2. Deep Inferior Epigastric Perforator Flap (DIEP) 2.3. Transverse Upper Gracilis (TUG) – or variation therein, including Diagonal Upper Gracilis (DUG) or L-Shaped Upper Gracilis (LUG) 2.4. Superior or Inferior Gluteal Artery Perforator Flap (S-GAP or I-GAP, respectively) 2.5. Lumbar perforator flaps 3. Multidisciplinary team recommends mastectomy regardless of response to upfront therapy (if required), either due to tumour size, multicentricity, or multifocality 4. Multidisciplinary team recommends post-mastectomy radiotherapy either due to tumour size or nodal status 5. Patients in whom upfront medical therapy has failed to facilitate breast conservation. The multidisciplinary team must agree that they need radiation after mastectomy, and they must be suitable candidates for microsurgical reconstruction 6. Multidisciplinary team has confirmed that they can define nodal radiation regions to be treated with available information
Exclusion criteria
Exclusion criteria: 1. Pregnancy-associated breast cancer, including women known to be pregnant at diagnosis, patients with a positive pregnancy test at screening, and/or women who are lactating in whom radiation therapy is contraindicated 2. Metastatic disease since breast reconstruction remains controversial in these cases, and would confound survival outcomes. If metastatic disease is discovered after randomisation and prior to protocol interventions, then the participant will be discontinued from protocol interventions. Follow-up information will still be collected, including questionnaires and photos. 3. Biopsy-proven synchronous contralateral breast cancer 4. Inflammatory cancer or skin involvement precluding skin-sparing mastectomy 5. Mastectomy for biopsy confirmed local recurrence after breast conserving surgery since typically these patients have already received whole breast radiation therapy 6. Failed breast-conserving surgery cases, requiring mastectomy to ensure clear resection margins 7. Patients receiving nipple-sparing mastectomy due to attendant risks associated with nipple aerolar vascularity and nipple areolar necrosis 8. Bleeding dyscrasias and anticoagulation, which are relative contraindications to autologous microvascular anastomosis 9. Unable to give informed consent to the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Patient-reported satisfaction with breasts 2 years after surgery was measured using BREAST-Q at 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Surgical flap and wound complications will be measured using the Breast Reconstruction and Valid Outcomes (BRAVO) study core outcome, as well as cosmesis and QoL, as follows at 3 months, year 1 and year 2: 1.1. Skin necrosis rates measured using the validated SKIN score 1.2. Reconstruction failure rates 2 weeks following surgery 1.3. Post-operative biopsy-proven fat necrosis rates 2. Surgical procedures to improve cosmesis, including rates of contralateral breast procedures, such as symmetrisation mammoplasty/mastopexy and fat grafting measured using data collected from electronic case report forms (eCRF) at one timepoint 3. Oncological outcomes, including pathological complete response (pCR), local recurrence rate, distant metastases, disease-free survival, and overall survival, measured using data collected from patient medical records at one timepoint 4. Radiological outcomes, including rates of radiation toxicity measured using data collected from the reporting system recommended by the Radiation Therapy Oncology Group (RTOG) at 2 years 5. Quality of life (QOL) will be measured using the validated generic health-related QoL EQ-5D-5L questionnaires at baseline, 3, 6, 9, 12 and 24 months post-operatively Aesthetic evaluation will be measured through the blinded expert panel assessment of anonymised 2-dimensional photographs taken at 1 year and 2 years after surgery using the validated Visser scale. 6. Treatment journey: pathway times (days) from diagnosis to locoregional therapy and between locoregional therapies (e.g. radiotherapy to surgery, etc), measured using study data at one timepoint 7. The health economic component will consider the joint distribution of cumulative hospital costs and QALYs. The EuroQoL EQ-5D-5L utility score will be used to adjust patient survival times to calculate Quality Adjusted Life Years (QALY), measured using study data at one timepoint | — |
Countries
England, United Kingdom
Contacts
Public ContactPuja Jadav
Outcome results
None listed