Title: Risk Assessment and Risk Reduction in Women with non Hereditary BC Risk
1Risk 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
2Breast 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
3Risk 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?
4Risk 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?
5Breast 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
6Belgian 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
7Breast 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
8Risk 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?
9Prevention 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.
10Breast 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
11Risk 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?
12How 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
13Breast 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.
14YES
51
NO
1
12
0
0
1
15Breast 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.
16(No Transcript)
17Breast 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.
18Risk 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?
19Breast Cancer Risk AssessmentOptions to Refine
Risk and Predict Benefit of Intervention
- To improve individualized risk assessments - To
tailor prevention care
Breast Density
Histologic or Cytologic evidence of atypia
20Mammographic 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.
21Risk of Breast Cancer According to Breast Density
in Premenopausal and Postmenopausal Women
RR5.3
RR3.4
Santen et al. N Engl J Med 2005353275
22Agreement 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).
23Breast Cancer Risk AssessmentOptions to Refine
Risk and Predict Benefit of Intervention
- To improve individualized risk assessments - To
tailor prevention care
Breast Density
Histologic or Cytologic evidence of atypia
24Proliferative 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
25Multifocal 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
26New 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
27Cytologic findings
RPFNA Ductal lavage
Non proliferative epithelium
Atypical hyperplasia
Adapted from Arun, B. et al. Clin Cancer Res
2007134943-4948
28Models 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
29Breast 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
30European Journal of Cancer Prevention 2008 in
press
31Breast 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 ?
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.
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34-
- Life is a sexually transmitted disease and
there is a 100 mortality rate. -
-
Woody Allen