Breast Cancer - Studies of Effects of Treatment in High-Risk Individuals

Translational Cancer Genetics Team

Section: Section of Cancer Genetics

Details of clinical studies of effects of treatment in breast cancer predisposition and hereditary non-polyposis colorectal cancer predisposition (HNPCC) gene carriers.

A Study of Survival in BRCA1/2 Gene Carriers who Develop Breast Cancer

L Kadouri, RA Eeles, F Lennard; in collaboration with J Peto, Section of Epidemiology; DF Easton, Cancer Research UK Genetic Epidemiology Unit, Strangeways Laboratory, Cambridge

We are determining whether there is any difference in survival after treatment for early breast cancer in women with germline mutations in the BRCA1/2 genes.

External Funding: Barclay Foundation, British Council, Monte Carlo Cancer Challenge, Cancer Research UK

A Prospective Observational Study of Outcome and Survival Endpoints in BRCA1/2 Gene Carriers who have Undergone Prophylactic Surgery (the PROSE Study)

RA Eeles, E Bancroft; in collaboration with G Gui, F MacNeill, N Roche, U Querci della Rovere, S Ebbs, Breast Unit; T Ind, D Barton, J Shepherd Gynaecology Unit; T Rebbeck, Philadelphia, USA

We are determining the incidence of cancer after prophylactic breast and ovarian surgery and its psychological implications. Initial studies have shown that such surgery reduces cancer risk by 90% in BRCA1/2 mutation carriers and prophylactic ovarian removal before 50 years halves the risk of a new primary breast cancer. Further follow up is in progress.

External Funding: National Institute of Health

Studies of Effects of Treatment and Dysmorphology in Breast Cancer Patients with Germline Mutations in Breast Cancer Predisposition Genes

S Shanley, RA Eeles; Z Kote-Jarai, A Ardern-Jones, E Bancroft, F Lennard, in collaboration with The Breast Unit, JR Yarnold, Section of Radiotherapy; I Fernando, Queen Elizabeth Hospital, Birmingham (Cancer Research UK SECRAB Trial); L Pierce, Department of Radiation Oncology, Philadelphia, USA; DF Easton, Cancer Research UK Genetic Epidemiology Unit, Cambridge, S Short, Gray Laboratory; S Hodgson, St George’s Hospital, D Eccles, Southampton, DGR Evans, Manchester

The late effects of radiation and chemotherapy in terms of toxcity and second tumour rate are being assessed in BRCA1/2 gene mutation carriers who develop breast cancer. When these individuals are examined for this study, a full dysmorphic examination is also undertaken to see if there is a particular phenotype associated with the presence of a mutation in BRCA1 or BRCA2.

External Funding: NHMRC Australia, Tony Maxse/Hugh Knowles Fund, Legacy of the late Marion Silcock, NIH, Monte Carlo Cancer Challenge, Cancer Research UK

 

Population Based Community Studies of Cancer Incidence in the Ashkenazim

RA Eeles, A Ward; in collaboration with M Ferris (General Practitioner), Edgware

We are determining the incidence of cancer in a population-based study encompassing a GP practice. A pilot study has shown a 1.4-fold increased risk of breast cancer in the Ashkenazim which is not observed in the non-Ashkenazim or Asians. The study is being extended to determine the degree of a positive family history in this population.

External Funding: NOCTEN

An Epidemiological Study of the Interaction of Lifestyle Factors and Germline Mutation in the BRCA1/2 Genes (the EMBRACE study)

RA Eeles, F Lennard, E Bancroft, L D’Mello ; in collaboration with D Easton, Cambridge

Questionnaires are used to record lifestyle factors which will be analysed for an interaction with germline mutation status of BRCA1/2 to determine lifestyle factors which may affect penetrance.

External Funding: Cancer Research UK, Monte Carlo Cancer Challenge

A Serial Collection of Biological Samples from Individuals with Germline Mutations in the BRCA1/2 Genes

RA Eeles, E Bancroft, L D’Mello

Serial samples are being collected of serum, lymphocytes, and urine annually from BRCA1/2 mutation carriers. Toenails are collected to measure selenium and one skin biopsy is taken to grow skin fibroblasts. A single sample is taken from non carriers. These samples will be used to find new markers of risk, predictors of cancer and genetic and biological associations with risk and cancer development.

External Funding: Cancer Research UK