Cover -- Half-title -- Title -- Copyright -- Dedication -- Contents -- Contributors -- Foreword -- Preface -- Acknowledgements -- Part 1 Molecular biology and natural history -- 1 Introduction -- Services for cancer genetics -- 2 Overview of the clinical genetics of breast cancer -- Introduction -- Family history as an indicator of predisposition to breast cancer -- Studies of familial breast cancer -- Molecular features -- Genes implicated in breast cancer predisposition -- BRCA1 -- Mutations -- Penetrance and prevalence -- BRCA2 -- Mutations -- Penetrance and prevalence -- Founder effects involving BRCA1 and BRCA2 -- Function of BRCA1 and BRCA2 proteins -- Heterogeneity -- Predictive testing for BRCA1 and BRCA2 -- 'BRCAX' -- Li-Fraumeni syndrome -- Low penetrance/modifier genes -- Conclusions -- REFERENCES -- 3 Cowden syndrome and related disorders -- Introduction -- Clinical aspects -- Epidemiology -- Diagnosis -- Cowden syndrome -- Bannayan-Riley-Ruvalcaba syndrome -- Genetics -- Genotype-phenotype associations -- Cowden syndrome -- Bannayan-Riley-Ruvalcaba syndrome -- Cryptic PHTS -- Differential diagnosis -- Clinical cancer genetic management -- Somatic PTEN alterations in sporadic tumours -- PTEN function -- Acknowledgements -- Note added in proof -- REFERENCES -- 4 Overview of the clinical genetics of ovarian cancer -- Summary -- Introduction -- Risks of ovarian cancer and their assessment -- Population risk -- Familial ovarian cancer -- Inherited genetic syndromes and ovarian cancer -- Hereditary breast/ovarian cancer -- Hereditary site-specific ovarian cancer syndrome -- Hereditary non-polyposis colorectal cancer syndrome -- Other syndromes -- Risk prediction models -- Clinical, pathological and outcome characteristics of BRCA-related ovarian cancer -- Age of onset -- Histopathological type -- Grade and stage.

Genotype-phenotype associations -- Pre-malignant and early invasive lesions -- Peritoneal cancer -- The natural history of BRCA1/2-related ovarian cancer -- Conclusion -- Acknowledgements -- REFERENCES -- 5 Ovarian and breast cancer as part of hereditary non-polyposis colorectal cancer (HNPCC) and other hereditary colorectal can -- Introduction -- Hereditary non-polyposis colorectal cancer -- Genetic basis -- Clinical features -- Do ovarian and breast cancer belong to the tumour spectrum of HNPCC? -- Recent data from the Dutch HNPCC registry -- Breast and ovarian cancer in other hereditary colorectal cancer syndromes -- Peutz-Jeghers syndrome -- Cowden syndrome -- Surveillance recommendations -- REFERENCES -- 6 The natural history of hereditary breast cancer -- Summary -- Introduction -- Ipsi- and contralateral breast cancer recurrences -- Linkage-based studies and survival -- Mutation-based studies and survival -- Perspectives and conclusion -- Acknowledgements -- REFERENCES -- 7 Pathology of the breast and ovary in mutation carriers -- Introduction -- Pathology of breast cancers in mutation carriers -- BRCA1-associated tumours -- BRCA2-associated tumours -- Molecular pathology of BRCA1/2-associated breast cancers -- Steroid hormone receptors -- c-erb-b2 -- TP53 -- Cell cycle proteins -- Familial ovarian cancer -- Classification of ovarian neoplasms -- Pathology of ovarian cancers in mutation carriers -- BRCA1-associated tumours -- BRCA2-associated tumours -- Grading and staging of familial ovarian cancers -- Malignant germ-cell and stromal-cell neoplasms in BRCA1 and BRCA2 mutation carriers -- Borderline ovarian neoplasms and in situ lesions in women with and without BRCA germline mutations -- REFERENCES -- 8 Risk estimation for familial breast and ovarian cancer -- Introduction -- Different basis for risk prediction -- Pedigree analysis.

Genetic analysis (mutation screening) -- Is the calculated carrier probability valid for the prediction of mutations? -- Summary -- Acknowledgements -- REFERENCES -- Part 2 Screening -- 9 Developing a cancer genetics service: a Welsh model -- Background -- Recommendations -- Primary care -- Cancer units -- Cancer centres -- Evaluation of services -- The developing service in Wales -- Primary care in the cancer genetics service for Wales -- Evaluation of the service -- Aims of the cancer genetics service for Wales -- Steering group -- Evaluation group -- Health service evaluation objectives -- Health economics objectives -- Development of benchmarks for the regional cancer genetics service -- Service delivery and information technology -- Looking to the future -- REFERENCES -- 10 Referral criteria for cancer genetics clinics -- Introduction -- Background -- Guidelines -- Breast cancer -- Ovarian cancer -- Risk assessment -- Methods -- Molecular genetic testing -- Summary -- REFERENCES -- 11 Guidelines for the development of cancer genetics services -- Identification of individuals with a genetic predisposition to cancer -- Primary care -- Genetic counsellors/genetic nurses -- Guidelines for risk estimation in individuals with a family history of cancer -- Calculation of risk of breast cancer -- Computer-aided risk estimation -- Guideline-based risk estimation -- Genetic counselling of 'at risk' individuals and families -- Management of patients in medium-and high-risk categories -- The individual and the individual's extended family -- Costs and benefits -- Genetic testing -- The principle of informed consent -- Disclosure of test results -- Ethical issues -- Equity of access -- Employment issues -- Insurance issues -- Stigmatization -- Regulation of commercial testing facilities -- Education and training -- Implementation -- Evaluation -- Conclusion.

REFERENCES -- 12 Cultural and educational aspects influencing the development of cancer genetics services in different European countries -- Standards -- Registries -- Healthcare structure -- Cancer genetics services -- Genetic counsellors -- Education -- Public awareness -- Conclusions -- REFERENCES -- 13 Screening, detection and survival patterns of breast and other cancers in high-risk families -- Background -- Early diagnosis -- Survival studies -- Prospective studies -- Retrospective studies -- Combined interpretation -- Population versus high-risk group screening -- Examination methods and interval between examinations -- Treatment -- Strategies for treatment -- Prophylaxis -- Associated cancers -- Summary -- Suggested guidelines -- Genetic counselling -- Follow-up examinations -- Prophylactic surgery -- Monitoring and evaluation of activity -- REFERENCES -- 14 Screening for familial ovarian cancer -- Why should we screen? -- Are there any reasons not to screen? -- What do we need from a screening test? -- What screening tests are in use? -- What are the current screening strategies? -- What data are available regarding screening in high-risk women? -- What is current practice? -- What are the current trials? -- Conclusions -- REFERENCES -- Part 3 Management -- 15 Management of BRCA1/2 mutation carriers -- Introduction -- Prevention -- Reducing the risk of first primary breast cancer -- Lifestyle modification -- Medical intervention (chemoprevention) -- Surgical intervention -- Reducing the risk of second primary breast cancer -- Reducing the risk of ovarian cancer for a woman with no previous cancer -- Medical intervention -- Surgical intervention -- Reducing the risk of cancers at other sites -- Prostate cancer -- Pancreas, head and neck, and stomach cancer -- Early detection -- Breast cancer -- Breast self-examination -- Clinical examination.

Mammography -- Ultrasonography -- Magnetic resonance imaging -- Other screening techniques -- Ovarian cancer -- Males at risk -- Prostate cancer -- Treatment -- Breast cancer -- Surgery -- Radiotherapy -- Chemotherapy -- Ovarian cancer -- Perspectives and conclusion -- REFERENCES -- 16 Management of familial ovarian cancer -- Should the management of familial ovarian cancer differ from that of sporadic ovarian cancer? -- Presentation -- Special investigations -- Management -- Surgery -- Chemotherapy -- Neoadjuvant chemotherapy with interval debulking -- Palliative care -- Prevention -- Prophylaxis -- Counselling -- Conclusion -- REFERENCES -- 17 Prophylactic mastectomy n mutation carriers -- Introduction -- Genetic counselling and the family history clinic -- The prophylactic mastectomy protocol -- Surgical technique -- Operative sequence -- Outcomes -- Follow-up -- Uptake -- REFERENCES -- 18 Psychosocial aspects of genetic counselling for breast and ovarian cancer -- Introduction -- Psychological distress associated with genetic counselling for breast/ovarian cancer -- Psychological distress amongst previously affected women -- Perceptions of risk -- Genetic testing -- Mutation searches and predictive testing -- Attitudes towards testing -- Brief note about gender differences -- Inconclusive results -- Psychological impact of results -- Effect of results on behaviour -- Conclusions -- REFERENCES -- 19 BRCA1/2 testing: uptake and its measurement -- Introduction -- The experience from other genetic tests -- Anticipated rates for BRCA1/2 -- Research into the potential uptake of BRCA1/2 testing -- The general population -- Hereditary breast/ovarian cancer families -- Calculating uptake -- What kind of test? -- What is the study population? -- Changes over time -- Attendance for education and counselling -- Eligibility -- Pedigree studies.

Research contexts.