Condition category
Cancer
Date applied
26/03/2018
Date assigned
20/04/2018
Last edited
20/04/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Current breast imaging methods mean that multiple breast cancers are being diagnosed in many women who are usually offered mastectomy to remove their whole breast with immediate or delayed breast reconstruction. However, these multiple smaller cancers may be treated using breast-saving surgery, called breast-conserving surgery, which is likely to occur currently in about a quarter of women. This breast-saving surgery aims to remove each cancer and to remodel the breast tissue, called a therapeutic mammoplasty. Therapeutic mammoplasty can be used to remove more than one cancer in the breast. Both skin and breast tissue are removed, leaving scars similar to those seen after a standard breast reduction. The aim of this study is to find out if breast-saving surgery is as safe as mastectomy in terms of controlling the rates of a cancer returning in the same breast or armpit, or elsewhere in the body. Currently, surgeons are unsure about the quality of the studies about the long-term safety of breast-saving surgery. However, some studies suggest that breast-saving surgery may be as safe as mastectomy, but there may be a slightly increased 5 and 10-year risk (around 2%) of the cancer returning in the remaining breast tissue. The potential safety of breast-saving surgery also depends on additional treatments of the breast tissue using radiotherapy and chemotherapy and/or endocrine treatments as well as bone strengthening drugs. All of these treatments can work together to kill possible microscopic cancer cells in the breast and reduce the chances of any cancer recurring in the breast. The study will also record women’s quality of life, satisfaction with the appearance of their breasts and the costs of the surgery types.

Who can participate?
Women aged over 40 with Multiple Ipsilateral Breast cancer (MIBC)

What does the study involve?
Participants are randomly allocated to undergo either breast-saving surgery or mastectomy (with or without reconstruction). Patients allocated to breast-saving surgery discuss with their surgeon whether it is possible to perform a breast reduction of their other breast either at the same time or at a later time. All women in this group receive radiotherapy to the whole breast plus possible extra doses to some of the lumpectomy sites. Breast surgery combines surgical removal of each breast cancer plus a cosmetic procedure, which occurs whilst they are under a general anaesthetic and takes 4-6 hours. Reduction of the opposite breast may occur 4-10 months later. Patients allocated to mastectomy and breast reconstruction may not require a breast reduction of the other breast. They may also not require radiotherapy except in 30-35% of women who are recommended for this after their surgery based on all their cancer results. The breast surgery combines surgical removal of the breast plus breast reconstruction either immediate or delayed. Delayed reconstruction occurs 10-12 months later. Other procedures like nipple reconstruction after mastectomy may occur at about 18 months or later. This gives the new breast time to settle into its permanent position. Each patient is followed up for 12 months after treatment. 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 are also invited to an optional interview at 12 months.

What are the possible benefits and risks of participating?
It is not yet known whether there will be any benefit to the patient by taking part in the study. However, it is hope that the information from the study will benefit women in the future who are diagnosed with multiple breast cancers. This small study will help with the design of a larger national study to include many more women. The risk associated with taking part in this study, for the women in breast saving group, is that one or both of the tumors/lumps may not be completely removed or that the residual tissue may develop cancer in the future. The increased risk of cancer returning is thought to be around 2% compared to mastectomy. In women allocated to breast saving surgery, there may also be about a 10% chance of needing a mastectomy because of cancer margins being positive after one or two attempts at saving the breast. Taking part in the study may have no extra risks over those for mastectomy and breast reconstruction. Both procedures can have some complications but these are not any different from having the surgery outside of the study and their frequencies are described in each treatment information booklet. Information and counselling on the risks of general anesthetic and radiotherapy as well as any possible side effects will be discussed with the patient as part of routine care.

Where is the study run from?
1. Manchester University NHS Foundation Trust (UK)
2. Royal Stoke University Hospital (UK)
3. Queen Alexandra Hospital (UK)
4. Doncaster and Bassetlaw Teaching Hospital (UK)
5. Queen Elizabeth Hospital (UK)
6. East Sussex Healthcare NHS Trust, Eastbourne Hospital/Conquest Hospital (UK)
7. Addenbrookes Hospital (UK)
8. St George's Hospital (UK)
9. New Victoria Hospital Glasgow (UK)
10. Royal Derby Hospital (UK)
11. The Nottingham Breast Institute City Hospital (UK)
12. King's College Hospital (UK)
13. Royal Cornwall Hospital (UK)
14. Royal Surrey County Hospital (UK)
15. York Teaching Hospital (UK)
16. Guy's Hospital (UK)
17. Leeds General Infirmary (UK)
18. John Radcliffe Hospital (UK)
19. Royal Liverpool Hospital (UK)
20. Frimley Park Hospital (UK)
21. Ipswich Hospital (UK)
22. Great Western Hospital (UK)
23. Royal Hampshire County Hospital (UK)
24. Royal Devon and Exeter Hospital (UK)
25. Llandough Hospital (UK)

When is the study starting and how long is it expected to run for?
April 2018 to October 2020

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Prof. Zöe Winters
z.winters@ucl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Zoe Winters

ORCID ID

Contact details

Surgical & Interventional Trials Unit
Charles Bell House (Third Floor)
43-45 Foley Street
London
W1W 7JN
United Kingdom
+44 (0)20 7679 9280
z.winters@ucl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

37198; 17/0048

Study information

Scientific 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? A randomised controlled feasibility study

Acronym

MIAMI

Study hypothesis

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.

The aim of this study is 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.

Ethics approval

London - City & East Research Ethics Committee, 14/03/2018, REC ref: 18/LO/0133

Study design

Randomised; Interventional; Design type: Treatment, Surgery

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Breast Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasm of breast

Intervention

This will comprise a multi-centre randomised controlled trial in women with Multiple Ipsilateral Breast cancer (MIBC) requiring surgery. Randomisation will be carried out using an online tool provided by Sealed Envelope, minimised by recruiting centre and multifocal/multicentric disease. Women who provide written informed consent will be randomised in a 1:1 ratio to one of two treatment groups and will be informed of the results after baseline questionnaires are completed. Participants will receive either Therapeutic Mammoplasty (TM) following excision of each cancer focus, or mastectomy (+/- reconstruction). 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 12 months.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

Feasibility of a larger trial, assessed using:
1. Numbers of women with more than one cancer in the same breast (MIBC) screened for the trial by 36 months
2. Numbers of eligible women based on trial criteria and suitable for therapeutic mammoplasty by 36 months
3. The proportion of women eligible for the trial who provide written informed consent by 36 months
4. Rate of compliance with allocated treatment and reason for deviation by 36 months

Secondary outcome measures

1. Reasons why patients accept or decline randomisation, assessed from patient-completed Qualitative Study questionnaire
2. Views of clinical staff assessed using qualitative interviews
3. Views of participating patients assessed using qualitative interviews

Overall trial start date

01/04/2018

Overall trial end date

31/10/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged >40 years with MIBC
2. Minimum of two invasive foci of breast cancer
3. Suitable for Therapeutic Mammoplasty
4. Fit for adjuvant therapy
5. Willing and able to provide written informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 50; UK Sample Size: 50

Participant 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

Recruitment start date

30/04/2018

Recruitment end date

31/07/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Manchester University NHS Foundation Trust
M23 9QZ

Trial participating centre

Royal Stoke University Hospital
ST4 6QG

Trial participating centre

Queen Alexandra Hospital
Portsmouth
PO6 3LY

Trial participating centre

Doncaster and Bassetlaw Teaching Hospital
DN2 5LT

Trial participating centre

Queen Elizabeth Hospital
Birmingham
B15 2TH

Trial participating centre

East Sussex Healthcare NHS Trust, Eastbourne Hospital/Conquest Hospital
BN21 2UD

Trial participating centre

Addenbrookes Hospital
Cambridge
CB2 0QQ

Trial participating centre

St George's Hospital
London
SW17 0QT

Trial participating centre

New Victoria Hospital Glasgow
G42 9LF

Trial participating centre

Royal Derby Hospital
DE22 3NE

Trial participating centre

The Nottingham Breast Institute City Hospital
NG5 1PB

Trial participating centre

King's College Hospital
London
SE5 9RS

Trial participating centre

Royal Cornwall Hospital
TR1 3LQ

Trial participating centre

Royal Surrey County Hospital
Guildford
GU2 7XX

Trial participating centre

York Teaching Hospital
YO31 8HE

Trial participating centre

Guy's Hospital
London
SE1 9RT

Trial participating centre

Leeds General Infirmary
LS1 3EX

Trial participating centre

John Radcliffe Hospital
Oxford
OX3 9DU

Trial participating centre

Royal Liverpool Hospital
L7 8XP

Trial participating centre

Frimley Park Hospital
GU16 7UJ

Trial participating centre

Ipswich Hospital
IP4 5PD

Trial participating centre

Great Western Hospital
Swindon
SN3 6BB

Trial participating centre

Royal Hampshire County Hospital
Winchester
SO22 5DG

Trial participating centre

Royal Devon and Exeter Hospital
EX2 5DW

Trial participating centre

Llandough Hospital
CF64 2XX

Sponsor information

Organisation

University College London

Sponsor details

Joint Research Office
1st Floor
Maple House – Suite B
149 Tottenham Court Road
London
W1T 7DN
United Kingdom
+44 (0)203 447 5274
randd@uclh.nhs.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Central Commissioning Facility (CCF); Grant Codes: PB-PG-1215-20009

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

A draft protocol for publication is in process. Planning to submit and publish protocol to open access journal. Planned publication of the results in a high-impact peer reviewed journal.

IPD sharing statement
The Surgical & Interventional Trials Unit (SITU) is committed to maximising the use of all trial data to achieve scientific knowledge. To this end, they welcome proposals for collaborative and noncollaborative projects. The MIAMI data sharing policy has been developed to follow a controlled access model for data sharing, which conforms to the MRC Policy on
Research Data Sharing. In this model, data is made as freely available as possible while safeguarding the privacy of participants, protecting confidential data and maintaining the reputation of the study and the study and its participants.
For general data sharing enquiries, please contact situ.office@ucl.ac.uk. For MIAMI specific requests please contact situ.miami@ucl.ac.uk. Data are available to bona-fide researchers with established scientific record. The data sharing model involves the submission of the Data Sharing Application Form (available from SITU), and the list of variables needed for the project. Please highlight the variables names in the Excel data dictionary (also available from the SITU). Approval for data release can only be considered after each study has published its most latest planned publication, and all requests will be submitted to the appropriate Trial Steering Committee for consideration. Upon approval of the application, applicants will be asked to sign a data sharing agreement. Within two weeks of the receipt of signed data sharing agreement, the data manager will release an anonymised dataset, tailored for this request.

Intention to publish date

31/10/2021

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes