Up to 10% of ovarian cancers can be attributed to an inherited genetic predisposition. Women at high risk of developing the disease can be identified from their family history of cancer, where certain types of cancer are seen in affected relatives (e.g. ovarian cancer, breast cancer). Currently, the only strategy available to reduce the risk of developing ovarian cancer is surgery to remove the ovaries and fallopian tubes. However, many women are unwilling to undergo risk-reducing surgery. The aim of this national study is to find out whether screening tests can pick up ovarian cancer at an early stage, when treatment is more likely to be successful.
UK FOCSS Centres
ISRCTN No - 32794457
UK CRN ID - 1069
Prospective single arm screening study.
- Screening with 4-monthly serum CA125 and annual transvaginal ultrasound scan of the ovaries.
- Collection of serial blood samples three times a year for retrospective analysis with novel tumour markers.
- To develop an optimised screening strategy for ovarian cancer in terms of the most appropriate screening tests, criteria for interpretation of results, screening interval, morbidity and cost in women at high risk because of a strong family history or inherited genetic predisposition.
- To establish a serum bank for future assessment of novel tumour markers.
Sensitivity, Specificity and Positive Predictive Value of the UKFOCSS screening strategy for the detection of primary epithelial ovarian and fallopian tube cancer.
Phase 1 3563 women
Phase 2 4531 women
Inclusion Criteria Eligibility is determined as follows:
The volunteer should either have been affected by one of the following cancers or be a first degree relative (FDR) of an affected family member. (Tubal and primary peritoneal cancers may be considered equivalent to ovarian cancer.)
Families with ovarian or ovarian & breast cancer
- ≥2 individuals with ovarian cancer who are FDR
- One ovarian cancer and 1 breast cancer <50 years who are FDR
- One ovarian cancer and 2 breast cancers < 60 years who are FDR
- Breast cancer in volunteer/ proband (≤45 years) and mother with both breast and ovarian cancer (in the same person)
- Breast cancer in volunteer/ proband (≤40 years) and sister with both breast and ovarian cancer (in the same person)
- Criteria 1, 2, and 3 (above) can be modified where paternal transmission is occurring i.e. families where affected relatives are related by second degree through an unaffected intervening male relative and there is an affected sister are eligible.
Families with a known gene mutation
- The family contains an affected individual with a mutation of one of the known OC predisposing genes, e.g. BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS1 and PMS2.
Families with colorectal cancer (HNPCC or Lynch syndrome)
- The family contains ≥3 individuals with a HNPCC related cancer*, who are FDR and ≥1 case is diagnosed before 50 years and the cancers affect ≥1 generation*HNPCC related cancers - colorectal, endometrial, small bowel, uretic and renal pelvic cancers
Families with only breast cancer*
- ≥4 breast cancers
3 breast cancers related by FDR
- one ≤30 years or
- all ≤40 years or
- one MBC (Male Breast Cancer) and one b/l breast cancer
Breast cancer in volunteer/ proband (≤50 years) and
- breast cancer in mother (age of onset being ≤30 years in one and ≤50 years in the other) or
- b/l breast cancer in mother (≤40 years onset) or
- one MBC and one b/l breast cancer
- Two MBC (one <40 years) in the family and proband is a FDR of one of them
Families with Ashkenazi Jewish ethnicity (additional criteria)*
AJ ethnicity and any one of the following:
- Breast cancer (<40 years) or bilateral breast cancer (first cancer <50 years) in volunteer/ proband, irrespective of FH (family history) of cancer
- Breast cancer in volunteer/ proband (<50 years) and one FDR with breast cancer (<50years) or ovarian cancer (any age) or MBC (any age)
- Breast cancer in volunteer/ proband (<60 years) and one FDR with breast cancer (<40 years) or ovarian cancer (any age) or MBC (any age)
- One FDR with ovarian cancer (<50 years)
- FDR with breast and ovarian cancer in the same woman (any age)
- Two FDR with breast cancer (<40 years)
- Two MBC (<60 years) in the family and proband is a FDR of one of them
*Families in these categories negative on full BRCA1 and BRCA2 screening are ineligible.
- Past history of bilateral oophorectomy (women with one or both fallopian tubes still present are eligible)
- Age <35 years
- Women participating in other ovarian cancer research trials
Definition of Ovarian Cancer’
For the purposes of determining a woman’s eligibility based on the occurrence of ovarian cancer in her family history, the term ‘ovarian cancer’ specifically refers to ‘epithelial ovarian cancer’ and does not include ‘borderline ovarian tumour’.
Eligible women were recruited via Clinical Genetics centres or collaborating medical departments (e.g. gynaecology, medical oncology).
Postal questionnaire at the end of screening (March 2012) and one year after screening has ended (April 2013).
Cancer and death flagging: Study participants are flagged through the appropriate central registry.
May 2002 – March 2012
Serum, plasma and DNA samples
- Blood samples from 5024 donors: 38708 serial serum samples, 34355 serial plasma samples
- DNA samples from 3935 donors: 3935 DNA samples
|Prof Ian Jacobs||Chief Investigator|
(UCL, University of Manchester)
|Prof Usha Menon||Co-Investigator|
|Dr James Mackay||Co-Investigator|
|Dr Steve Skates||Co-Investigator|
(Harvard Medical School)
|Dr Adam Rosenthal||Co-Investigator|
(Clinical Lead) (Barts Cancer Institute)
|Lindsay Fraser||Senior Research Associate, Trial Manager|
|Ms Sue Philpott||Senior Research Nurse, Data Manager, Safety Officer|
|Dr Ranjit Manchanda||Subspecialty Fellow|
|Dr Andy Ryan||Senior Data Manager|
|Mr Robert Liston||Senior Software Analyst|
|Dr Matthew Burnell||Statistician|
|Jessica Mozersky||Trial Manager|
|Lisa Perrault||Trial Coordinator, Data Manager|
|Philip Badman||Trial Coordinator, Data Manager, Safety Officer|
|Michele Johnson||Research Nurse|
|Kathryn Harris||Research Assistant|
|Dr Richard Hadwin||Subspecialty Fellow|
|Lanre Odunlami||Software Analyst|
|Jeremy Ford||Laboratory Manager|
|Richard Gnu||Bio Medical Scientist|
|Nuno Alvez||Medical Laboratory Assistant|
|Josie Cunningham||Medical Laboratory Assistant|
|Kristin Tamm||Medical Laboratory Assistant|
Data Monitoring Committee
|Prof Max Parmar (Chair)||Head, Cancer Division, MRC Clinical Trials Unit, London|
|Dr Shehla Mohammed||Consultant Clinical Geneticist and Head of Service for the Regional Genetics Centre, Clinical Genetics, Guy’s Hospital, London|
|Ms Karina Reynolds||Consultant Gynaecological Oncologist, Barts and The London, Gynaecological Cancer Centre|
Trial Steering Committee
|Dame Prof Julietta Patnick (Chair)||Director NHS Cancer Screening Programmes|
|Prof Diana Eccles||Professor of Cancer Genetics at the University of Southampton and Director of the University of Southampton Clinical Trials Unit|
|Prof Stephen Duffy||Professor of Cancer Screening, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine|
|Mr Derek Cruikshank||Consultant Gynaecological Oncologist, Clinical Director of Gynaecology, The James Cook University Hospital, Middlesbrough|
|Louise Bayne||Chief Executive, Ovacome|
Trial Management Committee
|Prof Ian Jacobs (Chair)||Professor of Gynaecological Cancer , Vice-President and Dean of the Faculty of Medical and Human Sciences, University of Manchester|
|Prof Usha Menon||Professor of Gynaecological Cancer, UCL Institute for Women’s Health|
|Dr James Mackay||Consultant Clinical Genetic Oncologist, UCL|
|Dr Steven Skates||Associate Professor, Department of Medicine, Harvard Medical School, Boston|
|Dr Adam Rosenthal||Senior Lecturer/Consultant Gynaecological Oncologist, Barts Cancer Institute|
|Lindsay Fraser||Senior Research Associate, UCL|
Outcome Review Committee
|Dr Liz Benjamin||Pathologist, UCLH NHS Trust|
|Dr Naveena Singh||Pathologist, Barts Health NHS Trust|
|Dr Adam Rosenthal||Gynae-Oncologist, Barts Health NHS Trust|
|Sue Philpott||Senior Research Nurse, UCL|
|NRES Committee||Cambridge South REC Ref 97/5/007|
Belfast City Hospital
Mr Hans Nagar (PI), Adrina O’Donnell, Rachel Hardy (Centre Contact)
Birmingham City Hospital
Mr James Nevin (PI), Brian Gammon (Centre Contact)
St Michael’s Hospital
Mr Bob Anderson (PI), Carole Shahin (Centre Contact)
Mr Robin Crawford (PI), Barbara Newcombe (Centre Contact)
Cardiff University Hospital
Mr Mark Rogers (PI), Sarah Scourfield (Centre Contact)
|Cheltenham & Gloucester|
Cheltenham General Hospital
Mr Rob Gornall (PI), Kate Trigg-Hogarth (Centre Contact)
Countess of Chester Hospital
Sharon Rowe (PI), Mary Aldous (Centre Contact)
Dr Sheila Pearson (PI), Angela Brit (Centre Contact)
Derby City General Hospital
Mr Howard Jenkins (PI), Samantha Crockett (Centre Contact)
University Hospital of North Durham
Dr Partha Sengupta (PI), Jean Dent (Centre Contact)
Western General Hospital
Dr Mary Porteous (PI), Susan MacKenzie (Centre Contact)
St John's Hospital
Mr Colin Partington (PI), Fay Munson (Centre Contact)
Queen Elizabeth Hospital
Mr Richard Edmondson (PI), Lillian Lee (Centre Contact)
Dr Rosemary Davidson (PI), Lesley Snadden, Sarah Gibson (Centre Contact)
Hull Royal Infirmary
Prof Mike Lind (PI), Jane Smales (Centre Contact)
Kettering General Hospital
Mr Robert Haughney (PI), Joanne Walsh (Centre Contact)
Queen Elizabeth the Queen Mother Hospital
Mr Andy Nordin (PI), Lin Tunkara (Centre Contact)
Mr Andreas Papadopoulos (PI), Sandra Burt (Centre Contact)
St James’s Hospital Leeds
Dr Carol Chu (PI), Emma O’Hara, Denise Hancock (Centre Contact)
Leicester Royal Infirmary
Mr Quentin Davies (PI), Julia Walker, Judy Maynard-Mills (Centre Contact)
Lincoln County Hospital
Mr Martin Lamb (PI), Olesya Francis (Centre Contact)
Liverpool Women’s Hospital
Dr Carol Benjamin (PI), Carole Ballard (Centre Contact)
Ms Sadaf Ghaem-Maghami (PI)
London, North West
Kennedy Galton Centre
Mr Huw Dorkins (PI)
London, UCLH (Barts / Guys)
University College Hospital (Barts Hospital, Guy’s Hospital)
Prof Usha Menon (PI), Saz Chamberlain (Centre Contact)
London, St George’s
St George's Hospital
Dr Kevin Hayes (PI)
St Mary’s Hospital
Prof Gareth Evans (PI), Karen Tricker (Centre Contact)
James Cook University Hospital
Dr Paul Brennan (PI), Gill Laidlaw (Centre Contact)
Milton Keynes General Hospital
Prof Christopher Lynch (PI), Heini Alderman (Centre Contact)
Northampton General Hospital
Mr Alistair Duncan (PI), Nancy Hopewell (Centre Contact)
Nottingham City Hospital
Ms Karin Williamson (PI), Teresa Parkes (Centre Contact)
Dr Lisa Walker (PI), Denise Fleming Brown (Centre Contact)
Royal Devon and Exeter Hospital / Royal Cornwall Hospital
Dr Carole Brewer (PI Exeter / Cornwall), Linda Garcia, Jacky Stewart, Emma Kent / Philip Harvey, Katharine Hill (Centre Contact)
Mr Tony Falconer (PI, Plymouth), Julie Pascoe (Centre Contact)
The Royal Marsden
Dr Rosalind Eeles (PI), Saz Chamberlain (Centre Contact)
Sheffield Children's Hospital
Dr Jackie Cook (PI), Cathryn Dow (Centre Contact)
Princess Anne Hospital
Prof Diana Eccles (PI)
North Staffordshire Royal Infirmary
Mr Vijay Menon (PI), Julie Robertson (Centre Contact)
Frimley Park Hospital
Mr Gareth Beynon (PI), Susan Richmond (Centre Contact)
Stoke Mandeville Hospital
Mr Damien Eustace (PI), Tracey Stammers (Centre Contact)
Dr Alex Murray (PI), Wendy Jones, Liwsi Protheroe (Centre Contact)
Glan Clywd Hospital
Dr Alex Murray (PI), Julie Greer (Centre Contact)
Wycombe General Hospital
Mr Damien Eustace (PI), Emma Hogbin (Centre Contact)
1. Widschwendter, M., M. Burnell, L. Fraser, A. N. Rosenthal, S. Philpott, D. Reisel, L. Dubeau, M. Cline, Y. Pan, P. C. Yi, D. Gareth Evans, I. J. Jacobs, U. Menon, C. E. Wood and W. C. Dougall (2015). "Osteoprotegerin (OPG), The Endogenous Inhibitor of Receptor Activator of NF-kappaB Ligand (RANKL), is Dysregulated in BRCA Mutation Carriers." EBioMedicine 2(10): 1331-1339.
2. Ramus, S. J., H. Song, E. Dicks, J. P. Tyrer, A. N. Rosenthal, M. P. Intermaggio, L. Fraser, A. Gentry-Maharaj, J. Hayward, S. Philpott, C. Anderson, C. K. Edlund, D. Conti, P. Harrington, D. Barrowdale, D. D. Bowtell, K. Alsop, G. Mitchell, A. S. Group, M. S. Cicek, J. M. Cunningham, B. L. Fridley, J. Alsop, M. Jimenez-Linan, S. Poblete, S. Lele, L. Sucheston-Campbell, K. B. Moysich, W. Sieh, V. McGuire, J. Lester, N. Bogdanova, M. Durst, P. Hillemanns, C. Ovarian Cancer Association, K. Odunsi, A. S. Whittemore, B. Y. Karlan, T. Dork, E. L. Goode, U. Menon, I. J. Jacobs, A. C. Antoniou, P. D. Pharoah and S. A. Gayther (2015). "Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer." J Natl Cancer Inst 107(11).
3. Song, H., E. Dicks, S. J. Ramus, J. P. Tyrer, M. P. Intermaggio, J. Hayward, C. K. Edlund, D. Conti, P. Harrington, L. Fraser, S. Philpott, C. Anderson, A. Rosenthal, A. Gentry-Maharaj, D. D. Bowtell, K. Alsop, M. S. Cicek, J. M. Cunningham, B. L. Fridley, J. Alsop, M. Jimenez-Linan, E. Hogdall, C. K. Hogdall, A. Jensen, S. K. Kjaer, J. Lubinski, T. Huzarski, A. Jakubowska, J. Gronwald, S. Poblete, S. Lele, L. Sucheston-Campbell, K. B. Moysich, K. Odunsi, E. L. Goode, U. Menon, I. J. Jacobs, S. A. Gayther and P. D. Pharoah (2015). "Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population." J Clin Oncol 33(26): 2901-2907.
4. Widschwendter, M., A. N. Rosenthal, S. Philpott, I. Rizzuto, L. Fraser, J. Hayward, M. P. Intermaggio, C. K. Edlund, S. J. Ramus, S. A. Gayther, L. Dubeau, E. O. Fourkala, A. Zaikin, U. Menon and I. J. Jacobs (2013). "The sex hormone system in carriers of BRCA1/2 mutations: a case-control study." Lancet Oncol 14(12): 1226-1232.
5. Rosenthal, A. N., L. Fraser, R. Manchanda, P. Badman, S. Philpott, J. Mozersky, R. Hadwin, F. H. Cafferty, E. Benjamin, N. Singh, D. G. Evans, D. M. Eccles, S. J. Skates, J. Mackay, U. Menon and I. J. Jacobs (2013). "Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule." J Clin Oncol 31(1): 49-57.
6. Lifford, K. J., A. Clements, L. Fraser, D. Lancastle and K. Brain (2013). "Catalysts to withdrawal from familial ovarian cancer screening for surgery and reactions to discontinued screening: a qualitative study." Fam Cancer 12(1): 19-26.
7. Lifford, K. J., A. Clements, L. Fraser, D. Lancastle, K. Brain and F. M. G. Psy (2013). "A qualitative study of women's experiences of familial ovarian cancer screening." Psychooncology 22(11): 2576-2584.
8. Rosenthal AN (2012). Ovarian cancer screening in the high-risk population; the UK Familial Ovarian Cancer Screening Study (UKFOCSS). Int J Gynecol Cancer vol. 22 Suppl 1, S27-S28. 10.1097/IGC.0b013e318251cc3f.
9. Brain, K. E., K. J. Lifford, L. Fraser, A. N. Rosenthal, M. T. Rogers, D. Lancastle, C. Phelps, E. K. Watson, A. Clements and U. Menon (2012). "Psychological outcomes of familial ovarian cancer screening: no evidence of long-term harm." Gynecol Oncol 127(3): 556-563.
10. Lifford, K. J., L. Fraser, A. N. Rosenthal, M. T. Rogers, D. Lancastle, C. Phelps, E. K. Watson, A. Clements, R. Iredale, I. Jacobs, U. Menon and K. E. Brain (2012). "Withdrawal from familial ovarian cancer screening for surgery: findings from a psychological evaluation study (PsyFOCS)." Gynecol Oncol 124(1): 158-163.
11. Lancastle, D., K. Brain and C. Phelps (2011). "Illness representations and distress in women undergoing screening for familial ovarian cancer." Psychol Health 26(12): 1659-1677.
Letters to editor
· Manchanda, R., A. Rosenthal, M. Burnell, L. Fraser, J. Mackay and S. Skates (2009). "Change in stage distribution observed with annual screening for ovarian cancer in BRCA carriers." J Med Genet 46(6): 423-424.
BOOK CHAPTERS AND REVIEW ARTICLES
1. Rosenthal, A., Menon, U. and Jacobs, I., 2007. Ovarian cancer screening, in Cancer of the Ovary, R.H. Reznek (ed), Cambridge University Press, Cambridge, UK, Chapter 3, pp.47-48.
2. Rosenthal, A.N., Menon, U. and Jacobs, I.J., 2006. Screening for ovarian cancer. Clinical obstetrics and gynecology, 49(3), pp.433-447.
3. Rosenthal, A. and Jacobs, I., 2006. Familial ovarian cancer screening. Best Practice & Research Clinical Obstetrics & Gynaecology, 20(2), pp.321-338.
CONFERENCES AND MEETINGS
o Rosenthal AN. Screening for Ovarian Cancer: UKFOCSS Phase 2 results update and where do we go from here? London Cancer Gynaecology & Breast Combined Research Day, London. 05 Feb 2015 (Invited lecture)
o Rosenthal AN. UK FOCSS: What have we learnt so far? New England Society of Gynaecological Oncologists, Rhode Island, USA, June 2014 (Invited lecture)
o Rosenthal AN. Update on the UKFOCSS. All Party Parliamentary Group on Ovarian Cancer, House of Commons, London, Jan 2014 (Invited lecture)
o Rosenthal AN, Fraser L, Philpott S, Manchanda R, Badman P, Hadwin R, Evans DG, Eccles DM, Skates SJ, Mackay J, Menon U & Jacobs IJ on behalf of the UK FOCSS collaborators. Results of intensive algorithm-based screening on UKFOCSS. European Society of Gynaecological Oncologists Meeting, 19-22 Oct 2013, Liverpool (Oral presentation)
o Philpott S, Fraser L, Manchanda R, Badman P, Skates SJ, Mackay J, Menon U, Jacobs IJ & Rosenthal AN. Detection of non-ovarian cancers on Phase 2 of the UK Familial Ovarian Cancer Screening Study (UK FOCSS). British Gynaecological Cancer Society Annual Meeting. Belfast, Northern Ireland. 20-21 June 2013. (Poster presentation)
o Rosenthal AN. UK FOCSS: What have we learnt so far? British Gynaecological Cancer Society Annual Meeting. Belfast, Northern Ireland. 20-21 June 2013. (Invited Lecture)
o Rosenthal AN, Fraser L, Philpott S, Manchanda R, Badman P, Hadwin R, Evans DG, Eccles DM, Skates SJ, Mackay J, Menon U & Jacobs IJ on behalf of the UK FOCSS collaborators. Results of 4-monthly Screening in the UK Familial Ovarian Cancer Screening Study (UK FOCSS Phase 2). Annual meeting of the American Society of Clinical Oncology, Chicago, USA. May/June 2013. (Oral presentation)
o Philpott S, Fraser L, Manchanda R, Badman P, Skates SJ, Mackay J, Menon U, Jacobs IJ & Rosenthal AN. Detection of non-ovarian cancers on Phase 2 of the UK Familial Ovarian Cancer Screening Study (UK FOCSS). UCL Institute for Women’s Health 8th Annual Meeting, London, May 2013. (Oral presentation)
o Rosenthal AN, on behalf of the UK FOCSS Investigators and Collaborators. Incidental diagnosis of endometrial cancer during high risk ovarian cancer screening. British Gynaecological Cancer Society, London, July 2012. (Poster presentation)
o Rosenthal AN, on behalf of the UK FOCSS Investigators and Collaborators. High Risk Population screening: The UK Familial Ovarian Cancer Screening Study (UK FOCSS) 4th International Conference on Ovarian Cancer Screening, London, United Kingdom, November 2011. (Oral presentation)
o Rosenthal AN, Fraser L, Manchanda R, Badman P, Philpott S, Skates SJ, Mackay J, Menon U & Jacobs IJ. UK FOCSS Phase 1 Screening. British Gynaecological Cancer Society Annual Meeting, Dublin, Ireland, November 2009. (Oral presentation)
o Rosenthal AN, Fraser L, Manchanda R, Badman P, Philpott S, Skates SJ, Mackay J, Menon U & Jacobs IJ. UK FOCSS results of Phase 1 Annual Screening. 16th Annual Meeting of the European Society of Gynaecological Oncology, Belgrade, Serbia. October 2009. (Poster presentation)
o Rosenthal AN, Fraser L, Manchanda R, Badman P, Philpott S, Mozersky J, Hadwin R, Skates SJ, Mackay J, Menon U & Jacobs IJ. UK FOCSS Phase 1 Screening. 15th Annual Meeting of the European Society of Gynaecological Oncology, Berlin, Germany, October-November 2007. (Oral presentation)
o Rosenthal AN, Fraser L, Badman P, Philpott S, Mozersky J, Skates SJ, Mackay J, Menon U & Jacobs IJ. UK FOCSS Interim Results of Annual Screening. 14th Annual Meeting of the European Society of Gynaecological Oncology, Istanbul, Turkey, October-November 2005. (Oral presentation)