Title: Can patients with multiple breast cancers in the same breast avoid mastectomy by having multiple lumpectomies to achieve equivalent rates of local breast cancer recurrence? (MIAMI feasibility RCT)
Funder: Department of Health and Social Care

Abstract: Background: Annually approximately 11-13,000 (20-24% of 55,000 breast cancers) UK women have more than one cancer in the same breast (multiple ipsilateral breast cancers: MIBC)[5]. Clinical perception recommends mastectomy to treat MIBC based on the perceived unstable breast with higher local recurrence rates[5]. UK surgeons practices showed that a minority (8-22%) recommend breast conserving surgery (BCS) or lumpectomies compared to mastectomy, with uncertainty about which treatment (53-67%), and clinical effectiveness based on moderate quality of cohort studies (Appendices: 3,8). Clinical trials for unifocal cancer show BCS is as effective as mastectomy, but no such trials of BCS versus mastectomy have yet been performed for MIBC. BCS usually refers to standard lumpectomy, but for this study the treatment will be oncoplastic BCS, comprising extended excisions of separate breast cancers followed by remodelling of remaining breast tissue including reduction mammoplasty optimising cosmetic outcomes[6,47,48]. Aims: This application is for a feasibility study to determine viability of a phase III randomised trial to assess whether BCS is as effective as mastectomy in preventing local recurrence at 5 years, and improves quality of life (QOL), cosmetic outcomes and patient satisfaction. The feasibility study aims to determine the rates of recruitment and randomisation, and acceptability of trial design to both patients and clinicians to inform the main study. Methods: In this feasibility study, 5 large UK centres (each with 400 or more new breast cancer cases annually) will recruit a total of 50 women (25 oncoplastic BCS plus 25 mastectomy) over 15 months, with 12 months follow-up. A successful study will be expanded into a much larger trial with 5-year follow-up, after first surgery. Study defined MIBC in Appendix: 2. Multifocal (MF) cancers comprise one &ldquo;disease site&rdquo; compared to two or more distant (separated by radiologically normal tissue requiring separate lumpectomies) &ldquo;disease sites&rdquo; in multicentric (MC) cancers[5]. Screened inclusion of all women >40 years with MIBC. Exclusion of women Oncoplastic BCS is the excision of either one disease site (multifocal) or >2 distant disease sites in multicentric cancers. Local multi-disciplinary teams will confirm surgical consensus for the feasibility of BCS and exclude women recommended for neoadjuvant treatments. The main trial primary outcome will be 5-year local recurrence including secondary outcomes and QOL. The feasibility study outcomes will include recruitment rates and acceptability of the trial design to patients and clinicians in addition to feasibility parameters relating to oncoplastic BCS such as: cancer margin clearance, numbers of surgical procedures, conversion to mastectomy and surgical complications. In this feasibility study, we will develop and test the health economic tools necessary to quantify healthcare resource usage and QOL. Qualitative interviews will explore women s views of the trial and acceptability of outcome measures. Health professional interviews will address their experiences of trial processes. Potential benefits: Currently 80-90% of UK women with MIBC are recommended for mastectomy. Previously, Public Health England did not distinguish numbers of women with MIBCs or their surgical treatments unless each cancer differed by tumour type[6]. UK pathology guidelines do not characterise separate cancers unless they differ by tumour type or histological grade[6]. This is compromising clinical outcomes[9,10,13-15]. If implemented in clinical practice, the results from a successful trial will decrease mastectomy rates in the UK by about 8000-9000 annually, which would be welcomed by most women facing this emotionally charged operation, and would be cost-saving for the NHS.

Lay abstract: Sometimes women have more than one breast cancer in the same breast at the same time. These women are usually offered a mastectomy (removal of that breast) and breast reconstruction. It may be possible to treat these patients by removing each cancer using breast-saving surgery (lumpectomies), used for women with only one breast cancer. Databases show that women who had lumpectomies did well, but they may have been healthier before the surgery than those who had a mastectomy. We need to be sure that lumpectomy is effective, safe, and acceptable for this patient group before making it universally available. Now is a good time to carry out this research as breast cancer treatments have improved and breast scans now show multiple breast cancers in 11,000 UK women annually. Before starting a large study, we will run a small study to make sure that women are willing to take part in a randomised trial. For this small study, we need 50 consenting women with more than one cancer to be randomised to either lumpectomies or mastectomy. These women will be followed up to one year initially and asked about their views and willingness to participate. This will help us design the bigger trial. The main trial will evaluate the rates of cancer returning and how this affects survival. We will record women s quality of life, assessing whether lumpectomies are satisfactory for women with more than one breast cancer. This trial has been discussed by patient groups who raised the importance of safety. They were reassured that trial patients will benefit from increased breast imaging, medical treatments linked to each cancer s biology and 5-year clinical follow-up outside of the study. Women interviewed expressed how important avoiding mastectomy was to them. Study results will be shown through publications, meetings, web-sites and charities.

Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS