MIAMI Safe Surgery for Multiple Breast Cancers (MIAMI)

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? A Randomised Controlled Feasibility Study.

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. The investigators need to be sure that lumpectomy is effective, safe, and acceptable for this patient group before making it universally available.

Study Overview

• Status: Completed
• Conditions: Breast Cancer, Unilateral
• Intervention / Treatment: Procedure: Mastectomy; Procedure: Therapeutic Mammoplasty

Detailed Description

The investigators will run a small study to evaluate whether a sufficient number of eligible patients can be identified and are willing to accept randomisation of the interventions in question. Recruitment and compliance rates of which will inform the feasibility and design of a larger trial. This will comprise a multi-centre randomised controlled trial in women with Multiple Ipsilateral Breast cancer (MIBC) requiring surgery. Participants will receive either Therapeutic Mammoplasty (TM) following excision of each cancer focus or mastectomy (+/- reconstruction). Patients will be randomised (1:1) into either intervention or control group.Therapeutic mammoplasty is an operation to remove breast cancer(s) whilst also significantly reducing the size of the breast. Therapeutic mammoplasty can be used to remove more than one cancer in the breast using separate lumpectomies. Both skin and breast tissue are removed, leaving scars similar to those seen after a standard breast reduction. Each patient is followed up for 12 months post treatment with a total of 50 patients recruited. Timings of the follow-up visits are aligned with standard of care practice for this patient population with quality of life questionnaires and clinical photographs completed before and after surgery. Twenty women will also be invited to an optional semi-structured interview at twelve months.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom
    • Addenbrooke's Hospital
  • Glasgow, United Kingdom
    • South Glasgow Hospitals - New Victoria Hospital / Gartnavel General Hospital
  • Ipswich, United Kingdom
    • Ipswich Hospital
  • London, United Kingdom
    • St. George's Hospital
  • Manchester, United Kingdom
    • Manchester University NHS Foundation Trust
  • Truro, United Kingdom
    • Royal Cornwall Hospital
  • Winchester, United Kingdom
    • Royal Hampshire Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. >40 years with MIBC, with the largest clinical cancer measuring 50mm as part of multifocal or multicentric "disease sites". 50mm may include the size of a single cancer and its surrounding small satellite cancers (6, 7). Clinically diagnosed (ultrasound and biopsy) either axillary lymph node negative or positive where axillary treatment depends on local policy
2. Two disease foci with a minimum of one invasive focus of breast cancer as defined within a "disease site"
3. Suitable for TM (best practice) using one large lumpectomy (multifocal) or any number of "distant" lumpectomies (multicentric) to excise "disease sites"
4. Fit for adjuvant therapy as per pre-operative evaluations (ECG, Chest X-ray, blood biochemistry)
5. Willing and able to provide written informed consent

Exclusion Criteria:

1. Neo-adjuvant therapy
2. Women considered high risk by local centre or known to have BRCA1/2 gene mutation
3. Ductal Carcinoma in situ (DCIS) only, and extensive DCIS
4. Bilateral breast cancers
5. Previous breast cancer (invasive or DCIS in either breast)
6. Pregnancy as confirmed on blood tests or ultrasound examination
7. Metastatic disease
8. Any previous type of breast radiotherapy
9. Significant other clinical risk factors and co-morbidities at the discretion of the treating clinicians
10. Previous or concomitant malignancy except adequately treated: non-melanomatous skin cancer; in situ carcinoma of the cervix and in situ melanoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Mastectomy +/- reconstruction; Either a simple mastectomy or skin sparing mastectomy technique will be used. Women in this arm will be offered either immediate or delayed breast reconstruction according to standard practice. Reconstructions will be followed by chemotherapy and/or endocrine therapy as determined by local clinicians . Chest wall and/or regional nodal radiotherapy will be prescribed according to local centre policy.	Procedure: Mastectomy; Removal of the whole breast.
ACTIVE_COMPARATOR: Therapeutic Mammoplasty; Therapeutic Mammoplasty (TM) comprises well-established surgical techniques involving volume displacement using breast reduction techniques, or volume replacement to maximize the volume of tissue that can be excised resulting in effective local control whilst maximizing cosmetic outcomes. This group will either have one "disease site" lumpectomy in the case of multifocal tumours or distant "disease site" lumpectomies in multicentric cancers.	Procedure: Therapeutic Mammoplasty; Excision via lumpectomy of multifocal or multicentric cancers with breast volume displacement techniques to maximise cosmetic outcomes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of women screened	Numbers of women with more than one cancer in the same breast (MIBC) screened for the trial	36 Months
Number of women eligible for the trial	Numbers of eligible women based on trial criteria and suitable for therapeutic mammoplasty	36 Months
Consent rate	The proportion of women eligible for the trial who provide written informed consent	36 Months
Compliance with trial procedures	Rate of compliance with allocated treatment and reason for deviation	36 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reasons why patients accept or decline randomisation	Tabulation of reasons why patients accept or decline randomisation (assessed from patient-completed Qualitative Study questionnaire)	36 Months
Qualitative research (clinical staff)	Tabulation of views of clinical staff following qualitative interviews	36 Months
Qualitative research (patients)	Tabulation of views of participating patients following qualitative interviews	36 Months

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: National Institute for Health Research, United Kingdom
• Investigators: Principal Investigator: Zoe Winters, University College, London

Publications and helpful links

General Publications

• Ingram J, Beasant L, Benson J, Brunt AM, Maxwell A, Harvey JR, Greenwood R, Roberts N, Williams N, Johnson D, Winters Z. The challenge of equipoise: qualitative interviews exploring the views of health professionals and women with multiple ipsilateral breast cancer on recruitment to a surgical randomised controlled feasibility trial. Pilot Feasibility Stud. 2022 Feb 28;8(1):46. doi: 10.1186/s40814-022-01007-1.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2017
• Primary Completion (ACTUAL): October 31, 2020
• Study Completion (ACTUAL): October 31, 2020

Study Registration Dates

• First Submitted: March 21, 2018
• First Submitted That Met QC Criteria: April 20, 2018
• First Posted (ACTUAL): May 2, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 18, 2021
• Last Update Submitted That Met QC Criteria: May 17, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Breast Cancer; Mastectomy; Therapeutic Mammoplasty; Multiple Ipsilateral Breast Cancers
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Unilateral Breast Neoplasms
• Other Study ID Numbers: 17/0048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All requests for data sharing will adhere to the UCL Surgical & Interventional Trials Unit (SITU) data sharing agreement policy. UCL Medical School is supportive of data sharing and will endeavour to assist in requests for data sharing. These data will be held on secure servers and will not be released to any third parties until all the main outputs from the studies have been published. All requests for access to the data will be formally requested through the use of a SITU data request form which will state the purpose, analysis and publication plans together with the named collaborators. All requests are dealt with on a case by case basis by SITU and the Chief Investigator. All requests will be logged and those successful will have a data transfer agreement which will specify appropriate acknowledgement of the Chief Investigator and study group, the sponsor, and funders.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No