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Risk Assessment and Risk Reduction in Women with non Hereditary BC Risk

Risk Assessment and Risk Reduction in Women with non Hereditary BC Risk. Fabienne Liebens MD Breast Unit Isala Breast Cancer Prevention Center CHU Saint Pierre – ULB-VUB Brussels. Breast Cancer Prevention WHO definitions. Primary prevention : covers all activities designed

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Risk Assessment and Risk Reduction in Women with non Hereditary BC Risk

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  1. Risk Assessment and Risk Reduction in Women with non Hereditary BC Risk Fabienne Liebens MD Breast Unit Isala Breast Cancer Prevention Center CHU Saint Pierre – ULB-VUB Brussels

  2. Breast Cancer PreventionWHO definitions • Primary prevention: covers all activities designed • to reduce the incidence of an illness in a population • to reduce the risk of new cases appearing • Secondary prevention:(early screening/diagnosis) • to reduce the prevalence of an illness in a population • to reduce its duration • Tertiary prevention: • to reduce the incidence of chronic incapacity or recurrences in a population, • to reduce the functional consequences of an illness • knowledge of independent risk factors of the disease • efficient risk reduction options FL - BBM2 - 2008

  3. Risk Assessment and Risk Reduction • Why do we need to address these issues? • Are there effective preventive strategies? • How do we assess BC risk? • How could we refine risk and predict benefit of interventions? • Challenges/Conclusion? FL - BBM2 - 2008

  4. Risk Assessment and Risk Reduction • Why do we need to address these issues? • Are there effective preventive strategies? • How do we assess BC risk? • How could we refine risk and predict benefit of interventions? • Challenges/Conclusion? FL - BBM2 - 2008

  5. Breast Cancer Risk AssessmentWhy ? Burden of BC European BC • 2006 • 430 000 cases • 132 000 deaths • Life time risk approaching 1 in 9 women • Demographic increase • Ageing population • Rise in young women • Wide differences in survival (16%) Eurocare 3 Adapted from Dr Nick Perry, Europa Donna Pan-European Conference- Amsterdam 2007 FL - BBM2 - 2008

  6. Belgian Cancer Patients’ Needs StudyFrequency of difficulties encountered Assessment of 38 types of difficulties (psychosocial, physical, marital, sexual…) More than 26 difficulties 6,3% From 21 to 25 difficulties 14,0% From 16 to 20 difficulties 28,7% From 11 to 15 difficulties 23,7% From 6 to 10 difficulties 17,9% From 1 to 5 difficulties 9,4% No difficulty 0 % % FL - BBM2 - 2008 2005- Courtesy of Darius Razavi and Isabelle Merckaert

  7. Breast Cancer Risk AssessmentWhy ? Risk Factors Breast Density 5-10% >25% Tamoxifen FL - BBM2 - 2008

  8. Risk Assessment and Risk Reduction • Why do we need to address these issues? • Are there effective prevention strategies? • How do we assess BC risk? • How could we refine risk and predict benefit of interventions? • Conclusion? FL - BBM2 - 2008

  9. Prevention strategies Adapted from Ozane EM. The Breast Journal 2006; 12: 103-133. FL - BBM2 - 2008

  10. Breast Cancer Risk AssessmentWhy ? Preventive strategies • Tamoxifen/raloxifen • Prophylactic surgery • Life style modifications the net risk/benefit ratio depends on the ability to quantify accurately a woman’s baseline likelihood of developing breast cancer Bishop J et al. The Health Economic of chemoprevention for Breast Cancer in Australia. Cancer Institute NSW, June 2008 FL - BBM2 - 2008

  11. Risk Assessment and Risk Reduction • Why do we need to address these issues? • Are there effective prevention strategies? • How do we assess BC risk? • How could we refine risk and predict benefit of interventions? • Conclusion? FL - BBM2 - 2008

  12. How do we assess BC risk? Models Gail, Claus, Tyrer Cuzick • The most common models used to predict a woman’s risk of breast cancer BRCAPRO, Frank, Cough • Used in a subset of the high-risk population to predict a woman’s probability of having a genetic mutation FL - BBM2 - 2008

  13. Breast Cancer Risk AssessmentHow ? Models • The Gail risk assessment model • estimates the risk of developing breast cancer in women undergoing annual screening. • Gail et al used data from 284,780 predominately white women in 28 participating centers of the Breast Cancer Detection Demonstration Project (BCDDP) to develop the model. • An unconditional logistic regression model • based on the ratio of risk in a woman with specified risk factors compared with the risk in a woman with no risk factors. FL - BBM2 - 2008

  14. YES 51 NO 1 12 0 0 1 FL - BBM2 - 2008

  15. Breast Cancer Risk AssessmentHow ? Models: Gail Limitations • Does not show great discriminatory power (predicts population risk well, but not individual risk). • 58%-65%-73% discriminatory • Not sufficient family history • Rockhill et al. J Natl Cancer Inst 93:358, 2001. • Tice. Breast Ca Res Treat 88(suppl 1):2004; abstract 13 • Cuzick. ASCO Educational Session 2005. Advantages • Use is widespread, with many forms of access (National Cancer Institute [NCI] Web site, handheld and computer applications). • Applicable to the largest number of women • Has been validated • Has been shown to be well calibrated. FL - BBM2 - 2008

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  17. Breast Cancer Risk AssessmentHow ? Models Conclusion: It is not sufficient to use only these mathematical models for the purpose of individual decision making regarding prevention interventions. FL - BBM2 - 2008

  18. Risk Assessment and Risk Reduction • Why do we need to address these issues? • Are there effective prevention strategies? • How do we assess BC risk? • How could we refine risk and predict benefit of interventions? • Conclusion? FL - BBM2 - 2008

  19. Breast Cancer Risk AssessmentOptions to Refine Risk and Predict Benefit of Intervention • - To improve individualized risk assessments • - To tailor prevention care Biomarkers Breast Density Histologic or Cytologic evidence of atypia FL - BBM2 - 2008

  20. Mammographic DensityOptions to Refine Risk and Predict Benefit of Intervention • Reflective of amount of epithelium, stroma, and fluid relative to fat. • Stroma and collagen make up the bulk of density. • Strong hereditary component Risk biomarker for both ER + and ER - cancers in pre- and postmenopausal women. Boyd et al. Lancet Oncol 2005 6(10):798-808.  McCormack VA et al. Cancer Epidemiol Biomarkers Prev. 2006 5(6):1159-69. Chen J. et al. J Natl Cancer Inst 2006; 98: 1215-1226. FL - BBM2 - 2008

  21. Risk of Breast Cancer According to Breast Density in Premenopausal and Postmenopausal Women RR=5.3 RR=3.4 FL - BBM2 - 2008 Santen et al. N Engl J Med 2005;353:275

  22. Agreement between computer-assisted quantitative measurement of mammographic breast density (MBD) and clinicians' assessment. F. Liebens et al. Proceedings of EBCC-6; European Journal of Cancer 2008; 6 (7):63. (abstract 45). FL - BBM2 - 2008

  23. Breast Cancer Risk AssessmentOptions to Refine Risk and Predict Benefit of Intervention • - To improve individualized risk assessments • - To tailor prevention care Biomarkers Breast Density Histologic or Cytologic evidence of atypia FL - BBM2 - 2008

  24. Proliferative benign breast disease with atypia 19/100 15y Degnim AC et al. JCO 2007 25:2671-2677 Elmore, J. G. et al. N Engl J Med 2005;353:297-299 FL - BBM2 - 2008

  25. Multifocal occult hyperplasia (+/- Atypia) is prevalent in young and middle aged high risk women But 80% of women have never had a diagnostic biopsy Hoogerbrugge et al. JCO 2003 21:41 Schnitt. Amer J Surg Pathology 2003 27:836 FL - BBM2 - 2008

  26. New methods Nipple aspiration fluid NAF Ductal Lavage DL Random peri areolar fine-needle aspiration RPFNA • RPFNA • Efficient way to obtain tissue for a prevention trial(Fabian et al Frontiers Prev Res 2005) • Cost effective to determine who gets chemoprevention (Ozanne et al Cancer Epidemiol Bio Prev 2004) • Women with AH more likely to enroll on NSABP Prevention Trial (Vogel et al JNCI 2002) and to take tamoxifen(Goldenberg VK Cancer Epidemiol Bio Prev 2007) cytology Risk Prediction FL - BBM2 - 2008

  27. Cytologic findings Adapted from Arun, B. et al. Clin Cancer Res 2007;13:4943-4948 FL - BBM2 - 2008

  28. Models for Phase II Chemoprevention Trials for Women at High Risk of BC Tissue Based Biomarkers R A N D O M I Z A T I O N Morphology Proliferation Study Agent RPFNA Random periareolar fine needle aspiration Repeat Biomarkers 6-12 months DL Ductal lavage NAF Nipple aspiration fluid Placebo Imaging-Based Biomarkers Mammographic Breast density Adapted from Fabian C. Endocrine related Cancer 2005 FL - BBM2 - 2008

  29. Breast Cancer Risk AssessmentWhy and How ? Clinical Practice • AIM of a consultation about breast cancer risk assessment • to determine if risk level is high enough to warrant special surveillance measures or prevention interventions, • if so, motivate those at high risk to partake in surveillance/prevention options • reassure those at low/moderate risk NCNN Breast Cancer risk reduction V2.2007 Kushi LH. CA Cancer J Clinic 2006 Sivell S. Cochrane databases of systematic reviews 2007 Kiluk J. Cancer Control 2007 FL - BBM2 - 2008

  30. FL - BBM2 - 2008 European Journal of Cancer Prevention 2008 in press

  31. Breast Cancer Risk AssessmentChallenges • Improve woman’s awareness/Knowledge? • Best practice in risk communication ? • Cost effectiveness ? • Best biomarker that predicts both risks and benefits fromintervention ? • Improve the skills of primary care providers ? FL - BBM2 - 2008

  32. “…Cancer is a multistage disease, not a single event, and doctors should emphasize cancer prevention in addition to cancer treatment and cure…” Peter Greenwald, Division of Cancer Prevention, National Cancer Institute. FL - BBM2 - 2008

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  34. “…Life is a sexually transmitted disease and there is a 100% mortality rate. …” Woody Allen FL - BBM2 - 2008

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