Breast Cancer and Ovarian Cancer Screening Studies in High-Risk Individuals

Translational Cancer Genetics Team

Section: Section of Cancer Genetics

Details of clinical studies in breast cancer predisposition gene carriers.

Nipple Fluid Aspiration and Ductal Lavage as a Screening Technique for Early Breast Cancer and Risk Assessment Tool in High Risk Women

I Locke, E Bancroft, Z Kote-Jarai, RA Eeles; in collaboration with G Gui, The Royal Marsden Breast Unit, C Isaacke, P Osin, A Nerurkar, Breakthrough Centre; G Mitchell, Peter MacAllum Institute, Australia.

We have completed volunteer studies of nipple fluid aspiration and have shown that the technique is feasible in 88% of women aged 35-50 years. Epithelial cells are obtained in about 30% of aspirates. Studies of PSA, CEA and CA15.3 levels and cellular yields in nipple fluid throughout the menstrual cycle have shown that there is no restriction about the timing of the aspirate in the menstrual cycle. A pilot study of ductal lavage has shown higher epithelial cell yields with high patient acceptability of the technique. Following this pilot work, serial aspirates and lavages are being performed on women with a germline mutation in BRCA1/2 in the Carrier Clinic to determine frequency of atypia and assess the sensitivity of these techniques in cancer detection. Those with atypia are offered duct endoscopy. Molecular studies are being performed on nipple aspirate and ductal lavage samples.

External Funding: Cancer Research UK

UKFOCSS Study of Ovarian Screening in High Risk Women

Investigators: Ian Jacobs (PI), Usha Menon, James Mackay, Steven Skates and Adam Rosenthal. RA Eeles is the local investigator at the Royal Marsden

Women at increased risk of ovarian cancer are offered genetic risk assessment and if appropriate, genetic testing. Screening with transvaginal ultrasound and the CA125 blood test within UKFOCSS is via the screening provision from the UKFOCSS centre at University College London (UCL).

External Funding: Cancer Research UK centrally, NCRN, Dr Eeles’ research fund, Royal Marsden NHS Foundation Trust.

A UK Multicentre Study of MRI versus Mammography as a Screening Measure in Women at High Risk of Breast Cancer (MARIBS): The Interaction of Genetic Risk with Screening Parameters

RA Eeles, F Lennard, G Kwan-Lim, L Pointon; Co-investigators D Easton, University of Cambridge; G Evans University of Manchester; S Gayther, UCL; R Warren, University of Cambridge; M Khazan, E Moore, M Leach, Magnetic Resonance Group, The National MARIBS Advisory Group.

We have coordinated a nationwide study of the comparison of breast magnetic resonance imaging (MRI) scans with mammography as a screening measure for unaffected breast cancer predisposition gene carriers or women at ≥50% risk of being a gene mutation carrier in high-risk families. Over 650 women have had both mammography and MRI breast scans performed and blood samples are available from 450 of these. A subset of Li-Fraumeni (LFS) families have had MRI only. The genes BRCA1  and  BRCA2  will be analysed by sequencing and rearrangements assessed by MLPA; in LFS the TP53  gene will be thus analysed. The family history will be assessed by various risk models. These will be correlated with MR density (density measurements supported by separate funding) and screening parameters e.g. recall, biopsy rates.

External Funding: Cancer Research UK