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

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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

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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 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

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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?

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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?

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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
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Belgian Cancer Patients Needs Study Frequency
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

2005- Courtesy of Darius Razavi and Isabelle
Merckaert
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Breast Cancer Risk AssessmentWhy ? Risk Factors
Genetic Factors Life Style Environment Hormonal history Breast Biopsy
BRCA1 BRCA2 Obesity Lack of physical activity Alcohol Irradiations Diet Tobacco Early menarche Late menopause Nulliparous Age of first pregnancy HRT ADH ALH DCIS LCIS
Breast Density
5-10
gt25
Tamoxifen
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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?

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Prevention strategies
Risk Factor Prevention Options Risk reduction
Gail risk 1.67 Tamoxifen/Raloxifen 49
BRCA1/2 Mastectomy 9095
BSOophorectomy Age lt35 ans 61 Age 3550 ans 51 Age gt50 yans 49
Tamoxifen 50
Atypia Tamoxifen 86
All women Life style modifications 3045
Adapted from Ozane EM. The Breast Journal 2006
12 103-133.
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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 womans 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
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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?

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How do we assess BC risk? Models

• Gail, Claus, Tyrer Cuzick
• The most common models used to predict a womans
  risk of breast cancer

• BRCAPRO, Frank, Cough
• Used in a subset of the high-risk population to
  predict a womans probability of having a genetic
  mutation

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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.

14
YES
51
NO
1
12
0
0
1
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Breast Cancer Risk AssessmentHow ? Models Gail

• 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.

• 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 93358, 2001.
• Tice. Breast Ca Res Treat 88(suppl 1)2004
  abstract 13
• Cuzick. ASCO Educational Session 2005.

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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.
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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?

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Breast Cancer Risk AssessmentOptions to Refine
Risk and Predict Benefit of Intervention

• Biomarkers

- To improve individualized risk assessments - To
tailor prevention care
Breast Density
Histologic or Cytologic evidence of atypia
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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.  McCo
rmack VA et al. Cancer Epidemiol Biomarkers Prev.
2006 5(6)1159-69. Chen J. et al. J Natl Cancer
Inst 2006 98 1215-1226.
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Risk of Breast Cancer According to Breast Density
in Premenopausal and Postmenopausal Women
RR5.3
RR3.4
Santen et al. N Engl J Med 2005353275
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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).
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Breast Cancer Risk AssessmentOptions to Refine
Risk and Predict Benefit of Intervention

• Biomarkers

- To improve individualized risk assessments - To
tailor prevention care
Breast Density
Histologic or Cytologic evidence of atypia
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Proliferative benign breast disease with atypia
19/100 15y
Degnim AC et al. JCO 2007 252671-2677 Elmore, J.
G. et al. N Engl J Med 2005353297-299
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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 2141 Schnitt. Amer
J Surg Pathology 2003 27836
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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
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Cytologic findings
RPFNA Ductal lavage
Non proliferative epithelium
Atypical hyperplasia
Adapted from Arun, B. et al. Clin Cancer Res
2007134943-4948
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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
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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
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European Journal of Cancer Prevention 2008 in
press
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Breast Cancer Risk AssessmentChallenges

• Improve womans 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
single event, and doctors should emphasize cancer
prevention in addition to cancer treatment and
cure



Peter Greenwald,

Division of Cancer Prevention,

National Cancer Institute.
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• Life is a sexually transmitted disease and
  there is a 100 mortality rate.
• 
  
• 
  
  Woody Allen