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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 - PowerPoint PPT Presentation
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Risk Assessment and Risk Risk Assessment and Risk Reduction in Women with Reduction in Women with non Hereditary BC Risknon Hereditary BC Risk
Fabienne Liebens MD
Breast Unit Isala Breast Cancer Prevention Center
CHU Saint Pierre – ULB-VUBBrussels
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Breast Cancer PreventionWHO definitions
Primary prevention: covers all activities designed
to reduce the incidence of an illness in a population to reduce the riskrisk 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
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Risk Assessment and Risk Risk Assessment and Risk ReductionReduction
• 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?
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Risk Assessment and Risk Risk Assessment and Risk ReductionReduction
• 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?
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Breast Cancer Risk AssessmentBreast Cancer Risk AssessmentWhy ? Burden of BCWhy ? Burden of BC
European BCEuropean 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
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Belgian Cancer Patients’ Needs Study Belgian Cancer Patients’ Needs Study Frequency of difficulties encounteredFrequency of difficulties encountered
%
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%
No difficulty 0 %
From 1 to 5 difficulties 9,4%
2005- Courtesy of Darius Razavi and Isabelle Merckaert
Assessment of 38 types of Assessment of 38 types of difficulties (psychosocial, physical, difficulties (psychosocial, physical, marital, sexual…)marital, sexual…)
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Breast Cancer Risk AssessmentBreast Cancer Risk AssessmentWhy ? Risk FactorsWhy ? Risk Factors
TamoxifenTamoxifen
Genetic Factors
Life Style
Environment
Hormonal Hormonal
historyhistory
Breast BiopsyBreast Biopsy
•BRCA1•BRCA2
ObesityObesityLack of physical Lack of physical activityactivityAlcoholAlcoholIrradiations
DietTobacco
•Early menarcheEarly menarche•Late menopauseLate menopause•NulliparousNulliparous•Age of first Age of first pregnancypregnancy•HRTHRT
-ADHADH-ALHALH-DCISDCIS-LCISLCIS
5-10% >25%>25%
Breast Density
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Risk Assessment and Risk Risk Assessment and Risk ReductionReduction
• 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?
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Prevention strategiesPrevention strategies
Risk Factor Prevention Options Risk reduction
Gail risk ≥1.67 Tamoxifen/Raloxifen 49%
BRCA1/2 Mastectomy 90–95%
BSOophorectomy Age <35 ans 61%
Age 35–50 ans 51%
Age >50 yans 49%
Tamoxifen 50%
Atypia Tamoxifen 86%
All women Life style modifications 30%–45%
Adapted from Ozane EM. The Breast Journal 2006; 12: 103-133.
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Breast Cancer Risk AssessmentBreast Cancer Risk AssessmentWhy ? Preventive strategiesWhy ? Preventive strategies
Tamoxifen/raloxifen Prophylactic surgery Life style modifications
the net risk/benefit ratio depends on the ability to quantify accuratelyto 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 2008June 2008
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Risk Assessment and Risk Risk Assessment and Risk ReductionReduction
• 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?
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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
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Breast Cancer Risk AssessmentBreast Cancer Risk AssessmentHow ? ModelsHow ? 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.
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5151
1212
11
YESYES
NONO
00
00
11
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Breast Cancer Risk AssessmentBreast Cancer Risk AssessmentHow ? Models: GailHow ? Models: Gail
AdvantagesAdvantages 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.
LimitationsLimitations 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. Rockhill et al. J Natl Cancer Inst J Natl Cancer Inst 93:358, 2001.93:358, 2001.Tice. Tice. Breast Ca Res Treat Breast Ca Res Treat 88(suppl 1):2004; 88(suppl 1):2004;
abstract 13abstract 13Cuzick. ASCO Educational Session 2005Cuzick. ASCO Educational Session 2005.
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Breast Cancer Risk AssessmentBreast Cancer Risk AssessmentHow ? ModelsHow ? Models
Conclusion: It is not sufficientIt is not sufficient to use only these mathematical models for the purpose of individual decision making regarding prevention interventions.
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Risk Assessment and Risk Risk Assessment and Risk ReductionReduction
• 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 How could we refine risk and predict benefit of interventions?predict benefit of interventions?
• Conclusion?
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Breast Cancer Risk AssessmentBreast Cancer Risk AssessmentOptions to Refine Risk and Predict Benefit of Intervention
BiomarkersBiomarkers
Breast DensityBreast Density Histologic or Cytologic Histologic or Cytologic evidence of atypiaevidence of atypia
- To improve individualized risk assessments- To tailor prevention care
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Mammographic DensityMammographic 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
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.
Risk biomarker for both ER + and ER - cancers in pre- and postmenopausal women.
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Risk of Breast Cancer According to Breast Density in Premenopausal and Postmenopausal Women
RR=3.4RR=3.4
RR=5.3RR=5.3
Santen et al. N Engl J Med 2005;353:275
FL - BBM2 - 2008Agreement 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).
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Breast Cancer Risk AssessmentBreast Cancer Risk AssessmentOptions to Refine Risk and Predict Benefit of Intervention
BiomarkersBiomarkers
Breast DensityBreast Density Histologic or Cytologic Histologic or Cytologic evidence of atypiaevidence of atypia
- To improve individualized risk assessments- To tailor prevention care
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Proliferative benign breast disease with atypia 19/100 15y
Degnim AC et al. JCO 2007 25:2671-2677Elmore, J. G. et al. N Engl J Med 2005;353:297-299
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Multifocal occult hyperplasia (+/- Multifocal occult hyperplasia (+/- Atypia) is prevalent in young and Atypia) is prevalent in young and
middle agedmiddle aged high risk womenhigh risk women
ButBut80% of women have never had a 80% of women have never had a
diagnostic biopsydiagnostic biopsy
Hoogerbrugge et al. JCO 2003 21:41Schnitt. Amer J Surg Pathology 2003 27:836
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New methods New methods Nipple aspiration
fluid
NAFNAF
cytology
Risk Prediction
Ductal Lavage
DL DL
Random peri areolar fine-needle aspiration
RPFNARPFNARPFNARPFNAEfficient 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)
FL - BBM2 - 2008Adapted from Arun, B. et al. Clin Cancer Res 2007;13:4943-4948
Cytologic findingsCytologic findingsRPFNARPFNA Ductal lavageDuctal lavage
Non proliferative epithelium
Atypical Atypical hyperplasiahyperplasia
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Models for Phase II Chemoprevention Models for Phase II Chemoprevention Trials for Women at High Risk of BC Trials for Women at High Risk of BC
Study Agent
Tissue Based Biomarkers
MorphologyProliferation
NAFNipple aspiration
fluid
DLDuctal lavage
RPFNARandom periareolar
fine needle aspiration
RANDOMIZATION
Placebo
Repeat Biomarkers6-12 months
Adapted from Fabian C. Endocrine related Cancer 2005
Imaging-Based BiomarkersMammographic Breast density
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AIM of a consultation about breast cancer risk assessment to determinedetermine if risk level is high
enough to warrant special surveillance measures or prevention interventions,
if so, motivatemotivate those at high risk to partake in surveillance/prevention options
reassureeassure those at low/moderate risk
Breast Cancer Risk AssessmentBreast Cancer Risk AssessmentWhy and How ? Clinical PracticeWhy and How ? Clinical Practice
NCNN Breast Cancer risk reduction V2.2007Kushi LH. CA Cancer J Clinic 2006Sivell S. Cochrane databases of systematic reviews 2007Kiluk J. Cancer Control 2007
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Breast Cancer Risk AssessmentBreast Cancer Risk AssessmentChallengesChallenges
Improve woman’s awareness/Knowledge? Best practice in risk communication ? Cost effectiveness ? Best biomarker that predicts both
risks and benefits from intervention ? Improve the skills of primary care
providers ?
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“…Cancer is a multistage disease, not a Cancer is a multistage disease, not a single event, and doctors should single event, and doctors should emphasize cancer prevention in addition emphasize cancer prevention in addition to cancer treatment and cureto cancer treatment and cure…”
Peter Greenwald, Division of Cancer Prevention, National Cancer Institute.
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“…Life is a sexually transmitted Life is a sexually transmitted disease and there is a 100% disease and there is a 100% mortality ratemortality rate. …”
Woody Allen
