MARIBS Primary objective

To test the hypothesis that MR imaging can be used with equal or better sensitivity and specificity than x-ray mammography for the screening of premenopausal women at high risk of developing breast cancer, in a non-randomised comparative study.

Secondary studies

• Psychological study - to measure the acceptability of MRI compared with x- ray mammography.

• Health technology assessment - to assess the diagnostic impact and therapeutic impact of MRI as a screening tool.

• Economic evaluation.

• Retrospective analysis to determine the optimum image analysis methodology

End Points

The detection and classification of lesions at imaging, as compared with the true incidence of cancer (verified by biopsy; excision; and follow-up by (i) flagging at the National Health Service Central Register (NHSCR), and (ii) by active follow-up through familial cancer clinics and General Practitioners).

Number of centres

21 genetics clinics

21 MRI centres

Screening protocol

Women are invited to attend for annual examinations for the duration of the study, commencing 12 months after any previous mammogram. MRI and x-ray mammography will be performed at each visit. The images from both modalities will be independently double read.

MRI examination

Strict measurement and analysis protocols have been established for this study. MR screening will be performed on MR systems with field strengths of 1 T or 1.5 T, actively screened gradients and dedicated bilateral breast coils. Multi-parametric analysis (including morphology, qualitative and quantitative contrast agent uptake) extracts the maximum diagnostic information from each MR study.

The most effective strategy for achieving a high degree of accuracy uses a high-resolution technique to achieve maximum sensitivity and a fast-scanning technique to achieve maximum specificity (dynamic observation of signal enhancement). Given the capabilities of current equipment, satisfactory sensitivity can only be achieved at the expense of specificity. Thus to achieve satisfactory overall sensitivity and specificity, a two stage MR imaging procedure has been adopted-

Visit A high-sensitivity MRI examination of both breasts, carried out between days 6-16 of the menstrual cycle.

This is followed in women with equivocal results by-

Visit B high-specificity examination of the equivocal area to be carried out 2 weeks later i.e. during a different phase of the menstrual cycle.

Mammography

Two-view mammography is performed in accordance with the guidelines of the UK National Health Service Breast Screening Programme.

Eligibility criteria

Group 1: Women aged 35 to 49 who are

a) gene carriers of BRCA1 or BRCA2, or

b) at a 1 in 2 risk of carrying BRCA1 or BRCA2 because of a known mutation in a parent or sibling, or

c) at a 1 in 2 risk of carrying BRCA1 or BRCA2 because of family history, i.e. in close relatives, there are

i) 4 or more cases of female breast cancer below the age of 60

ii) 4 or more cases of female breast and ovarian cancer where the breast cancer is below the age of 60 and the ovarian cancer is at any age

iii) 4 or more cases of female and male breast cancer where the female cancer is below the age of 60 and the male cancer is at any age

Group 2: Women aged 25 to 49 who are

a) gene carriers of p53, or

b) at a 1 in 2 risk of carrying p53 because of a known mutation in a parent or sibling, or

c) at a 1 in 2 risk of carrying p53 because of family history, i.e. a classical Li-Fraumeni family.

Exclusions

1) Previous breast cancer (including DCIS.)

2) Terminal illness, or life expectancy of less than 5 years.

3) Pregnancy or breast-feeding (recruitment suspended until breast-feeding has finished.)

4) Current chemotherapy (recruitment suspended until 6 months after treatment ceases. Exclusion 2, above, still applies.)

Symptomatic cohort (recruitment finished)

A "symptomatic cohort" of women were also scanned. These were women with a range of breast conditions, both benign and malignant, who were scheduled for biopsy or FNA. An initial analysis of the "symptomatic cohort" is currently underway which is looking at the reader compatibility and assessing the factors which are specific to MR system type. Also, the MR images will be compared with the pathology to determine the important quantitative and qualitative factors in diagnosing cancer.

Recruitment

839 high-risk and 140 symptomatic women have been recruited and scanned in 21 centres.

Recruitment closed on 31st March 2003. Scanning was completed on 31st March 2004. There are data on over 2000 scans on nearly 700 high-risk women. Full results and analysis will be available in early 2005.

Funding

The study is supported by the Medical Research Council (MRC) and the National Health Service Research and Development Board (NHS R&D).

Recruiting sites

ABE	Prof. Neva Haites, Professor of Medical Genetics, Department of Medical Genetics, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD
BEL	Dr Patrick Morrison, Consultant Geneticist, Dept. of Medical Genetics, Belfast City Hospital, Belfast, Northern Ireland, BT9 7AB
BIR	Dr Trevor Cole, Consultant Geneticist, Clinical Genetics Unit, Birmingham Maternity Hospital, Edgbaston, Birmingham, B15 2TG
BRI	Mr Zen Rayter, Consultant Surgeon, Bristol Royal Infirmary, Bristol, BS2 8HW
BRF	Mr Simon Cawthorn, Consultant Surgeon, Frenchay Breast Care Centre, Frenchay Healthcare NHS Trust, Frenchay Hospital, Bristol, BS16 1LE
CAM	Ms Barbara Newcombe, Research Nurse, CRC Department of Oncology, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, CB2 2XY
DUN	Dr David Goudie, Clinical Geneticist, Ninewells Hospital, Dundee, DD1 9SY
EDI	Prof. Michael Steel, Professor in Medical Science, University of St Andrew's, Bute Medical Building, St Andrews, SCOTLAND, KY16 9TS
GLA	Dr Rosemarie Davidson, Consultant Geneticist, Duncan Guthrie Institute of Medical Genetics, Yorkhill, GLASGOW, G3 8SJ
LSG	Dr Tessa Homfray, Consultant Geneticist, St. George's Hospital Medical School, Level 01 Cranmer Terrace, Jenner Wing, London, SW17 0RE
LGS	Dr Shirley Hodgson, Clinical Geneticist, Division of Medical and Molecular Genetics, 7th/8th Floor Guys Tower, Guy's Hospital, London, SE1 9RT
LEE	Dr Carol Chu, Dept. of Genetics, St James's Hospital, Beckett Street, Leeds, LS9 7TF
LIV	Dr Ian Ellis, Senior Lecturer in Clinical Genetics, Dept. of Clinical Genetics, Alder Hey Childrens Hospital, Eaton Road, Liverpool, L12 2AP
MAN/MMS	Prof Gareth Evans, Consultant Geneticist, Regional Genetic Service, St Mary's Hospital, Hathersage Road, Manchester, M13 9JH
NEW	Dr Fiona Douglas, Consultant Geneticist, Dept. of Genetics, Royal Victoria Infirmary, Newcastle Upon Tyne, NE1 4LP
NWP	Dr Joan Paterson, Consultant Geneticist, Kennedy Galton Centre, Northwick Park and St Marks Hospitals, Watford Road, Harrow, HA1 3UJ
SHE	Dr Oliver Quarrell, Consultant in Clinical Genetics, North Trent Clinical Genetics, Sheffield Childrens Hospital, Western Bank, Sheffield, S10 2TH
SOU	Dr Diana Eccles, Consultant Geneticist, Wessex Clinical Genetics Service, Level G Princess Anne Hospital, Southampton, SO16 5YA
SUT	Dr Ros Eeles, Consultant Geneticist, Cancer Genetics Clinic, The Royal Marsden NHS Trust, Sutton, Surrey, SM2 5PT

Scanning Centres

ABE	Prof Fiona Gilbert, Professor of Radiology, Department of Radiology, Lilian Sutton Building, Foresterhill, Aberdeen, AB25 2ZD
BAR	Dr Glenda Kaplan, Consultant Radiologist, X-Ray Department, Barnet Hospital, Wellhouse Lane, Barnet, HERTS, EN5 3DJ
BEL	Dr Graham Crothers, Radiologist, Carrickmannon House, Royal Hospitals Trust, Grosvenor Road, Belfast, BT12 6BA
BIR	Dr Colin Walker, Consultant Radiologist, Selly Oak Hospital, Raddlebarn Road, Birmingham, B29 6JB
BRI	Dr Angela Jones, Radiologist, Avon Breast Screening, Central Health Clinic, Tower Hill, Bristol, BS2 0JD
BRF	Dr Nicky Slack, Consultant Radiologist, Department of Radiology, Frenchay Healthcare NHS Trust, Frenchay Hospital, Bristol, BS16 1LE
SUT	Dr Preminda Kessar, Consultant Radiologist, Radiology Department, The Royal Marsden NHS Trust, Sutton, Surrey, SM2 5PT
CAM	Dr Ruth Warren, Consultant Radiologist, Breast Screening Centre - Box 97, Addenbrooke's Hospital, Cambridge, CB2 2QQ
DUN	Dr Declan Sheppard, Lead MRI Radiologist, Ninewells Hospital, Dundee, DD1 9SY
EDI	Dr James Walsh, Consultant Radiologist, Radiology Dept, Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh, EH3 9YW
GLA	Dr Janet Litherland, Consultant Radiologist, Dept. of Radiology, Royal Infirmary, 16, Alexandra Parade, Glasgow, G31 2ER
GLA	Dr Laura Wilkinson, Consultant Radiologist, MRI Scanning, The Western Infirmary, Dumbarton Road, Glasgow, G11 6NT
LGS	Dr Sheila Rankin, Clinical Director, X Ray Dept, Guys Hospital, St Thomas Street, London, SE1 9RT
LEE/SHE	Prof Lindsay Turnbull, Clinical Senior Lecturer/Hon. Consultant, Centre for Magnetic Resonance Investigations, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ
LIV	Prof Graham Whitehouse, Professor of Diagnostic Radiology & Director of Mariarc, MRI Analysis Research Centre, The University of Liverpool, Pembroke Place, Liverpool, L69 3BX
MAN	Dr Caroline Boggis, Consultant Radiologist, Nightingale Centre, Nell Lane, West Didsbury, Manchester, M20 0PT
MMS	Dr Jane Hawnaur, Consultant Radiologist, Department of Clinical Radiology, Manchester Royal Informary, Oxford Road, Manchester, M13 9WL
MVH/SUT	Dr Anwar Padhani, Consultant Radiologist, The Paul Strickland Scanner Centre, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex, HA6 2RN
NEW	Dr Alan Coulthard, Consultant Radiologist, MRI Unit, Victoria Wing Radiology Dept., Royal Victoria Infirmary, Newcastle Upon Tyne, NE1 4LP
NWP/SUT	Dr Will Teh, Consultant Radiologist, Department of Radiology, Northwick Park and St Marks Hospitals, Watford Road, Harrow, HA1 3UJ
SOU	Dr Caroline Rubin, Consultant Radiologist, Southampton & Salisbury Breast Screening Unit, Royal South Hants Hospital, Brintons Terrace off St Marys Road, Southampton, SO14 0YG

MARIBS Study Aims

Breast Group Links

Current Topics

Screening Links

HEADLINES

MARIBS Primary objective

Mammography

Eligibility criteria

Exclusions

Recruiting sites