Oncogenetic testing and follow-up for women with familial breast/ovarian cancer, Li-Fraumeni syndrome and Cowden syndrome
Authors: Robays Jo , Stordeur Sabine , Hulstaert Frank , van Maerken Tom , Claes Kathleen , Janin Nicolas , Matthijs Gert , 't Kint de Roodenbeke Daphné , Berlière Martine , Wildiers Hans , Poppe Bruce 
Published: January 2025

SCIENTIFIC REPORT .6 -- 1 INTRODUCTION 6 -- 1.1 BACKGROUND 6 -- 1.2 THE NEED FOR A GUIDELINE .7 -- 1.3 SCOPE 7 -- 1.4 REMIT OF THE GUIDELINE 8 -- 1.4.1 Overall objectives 8 -- 1.4.2 Target users of the guideline 8 -- 1.5 STATEMENT OF INTENT .8 -- 1.6 FUNDING AND DECLARATION OF INTEREST 8 -- 2 METHODOLOGY 9 -- 2.1 INTRODUCTION 9 -- 2.2 THE GUIDELINE DEVELOPMENT GROUP 9 -- 2.3 CLINICAL RESEARCH QUESTIONS .9 -- 2.4 GENERAL APPROACH .9 -- 2.5 LITERATURE SEARCH AND STUDY SELECTION .10 -- 2.5.1 Study design 10 -- 2.5.2 Databases and date limits 10 -- 2.5.3 Search strategy .10 -- 2.6 QUALITY APPRAISAL .11 -- 2.6.1 Clinical practice guidelines 11 -- 2.6.2 Systematic reviews .11 -- 2.7 DATA EXTRACTION .11 -- 2.8 GRADING EVIDENCE .11 -- 2.9 FORMULATION OF RECOMMENDATIONS 11 -- 2.10 EXTERNAL REVIEW 11 -- 2.10.1 Healthcare professionals 11 -- 2.10.2 Patient representatives .12 -- 2.11 FINAL VALIDATION 12 -- 3 CLINICAL RECOMMENDATIONS 13 -- 3.1 HEREDITARY BREAST CANCER.13 -- 3.1.1 Criteria for referral to a centre of human genetics specialized in cancer genetics and follow-up of women at-risk of hereditary breast cancer 13 -- 3.1.2 Models that assess the risk of carrying a germline mutation, such as BRCA1, BRCA2 and TP53 mutations .13 -- 3.1.3 Genes with low- and moderate-penetrance 14 -- 3.1.4 Screening and follow-up of patients identified to be at risk .15 -- 3.2 LI-FRAUMENI SYNDROME 20 -- 3.2.1 Introduction .20 -- 3.2.2 Diagnostic testing criteria for Li-Fraumeni syndrome 21 -- 3.2.3 Follow-up of patients with Li-Fraumeni syndrome 22 -- 3.3 COWDEN SYNDROME OR PTEN HAMARTOMA TUMOUR SYNDROME (PHTS) 26 -- 3.3.1 Introduction .26 -- 3.3.2 Diagnostic testing criteria and diagnostic criteria for Cowden syndrome. 26 -- 3.3.3 Follow-up of patients with Cowden syndrome 27 -- 5 IMPLEMENTATION AND UPDATING OF THE GUIDELINE .32 -- 5.1 IMPLEMENTATION 32 -- 5.1.1 Multidisciplinary approach 32 -- 5.1.2 Patient-centered care .32 -- 5.1.3 Barriers and facilitators for implementation of this guideline .32 -- 5.1.4 Actors of the implementation of this guideline 33 -- 5.2 MONITORING THE QUALITY OF CARE 33 -- 5.3 GUIDELINE UPDATE 33 -- 5.4 RESEARCH AGENDA .33 -- APPENDICES 34 -- APPENDIX 1. GDG MEMBERS .34 -- APPENDIX 2. SEARCH STRATEGIES 35 -- APPENDIX 2.1. HEREDITARY BREAST CANCER .35 -- APPENDIX 2.2. COWDEN 51 -- APPENDIX 2.3. LI-FRAUMENI SYNDROME 58 -- APPENDIX 3. EVIDENCE TABLES .65 -- APPENDIX 3.1. NICE RECOMMENDATIONS FOR GENETIC TESTING AND FOLLOW-UP OF FAMILIAL BREAST CANCER. .65 -- APPENDIX 3.2. GENETIC VARIANTS WITH A SIGNIFICANT ASSOCIATION WITH BREAST-CANCER RISK IN META-ANALYSIS12 .69 -- APPENDIX 4. LIST OF META-ANALYSES OF ASSOCIATIONS BETWEEN GENETIC VARIANTS AND BREAST CANCERS .70 -- APPENDIX 4.1. META-ANALYSES THAT GIVE NO OR INSUFFICIENT EVIDENCE FOR AN ASSOCIATION, OR EVIDENCE OF NO ASSOCIATION OR PROTECTIVE EFFECT .70 -- APPENDIX 4.2. META-ANALYSES SHOWING EVIDENCE FOR A WEAK OR A MODERATE ASSOCIATION .75 -- APPENDIX 5. GUIDELINES FOR HEREDITARY BREAST AND/OR OVARIAN CANCER SYNDROME DIAGNOSTIC TESTING CRITERIA 76 -- APPENDIX 6. DIFFERENT CRITERIA PUT FORWARD FOR LI-FRAUMENI SYNDROME 77 -- APPENDIX 7. REVISED DIAGNOSTIC CRITERIA FOR COWDEN SYNDROME .78 -- APPENDIX 8. NCCN TESTING CRITERIA FOR COWDEN SYNDROME 80 -- APPENDIX 8.1. EVIDENCE TABLES OF COHORT STUDIES ASSESSING CANCER RISK IN COWDEN SYNDROME 82 -- REFERENCES .85