breast cancer risk assessment: how and why
TRANSCRIPT
Cancer Risk AssessmentThe Why and How for Affected and
Unaffected Patients
Kevin S. Hughes, MD, FACSFounder: Hughes RiskApps.LLC
Co-Director, Avon Comprehensive Breast Evaluation Center
Massachusetts General Hospital
Associate Professor of Surgery
Harvard Medical School
Medical Director
Bermuda Cancer Genetics and Risk Assessment Clinic
Why evaluate risk
Not identifying high risk individuals will lead to unnecessary morbidity and death
Cancer Risk
Breast 50-87% 50-87%
Ovary 40-60% 10-20%
Breast 6%
F
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BRCA1 BRCA2
Hereditary vs Sporadic CancerKnudson’s 2 hit hypothesis
HEREDITARY CANCER
SPORADIC CANCER
18 years of BRCA testing
Female Carriers in the US ~560,000 to 720,000
Carriers found ~70,000, mostly affected
95% of unaffected carriers remain unaware and mismanaged
More genes to test for: Breast
• 1781 HBOC patients
• 25-Gene Panel (MyRisk)
– 13.5% had a mutation
• 9.3% in BRCA 1 or 2
• 4.2% in at least one other gene
More genes to test for: Breast
Tung et al ACMG2014
More genes to test for: Ovary
More genes to test for: Ovary• 360 women
• Ovarian
• Primary peritoneal
• Fallopian tube cancer
• 21 gene panel (12 found)
• 24% had a mutation
– 18% BRCA 1/2
– 6% another gene
• 30% carriers had no family history
• 35% of patients were > 60 y.o.
University of Washington Walsh et al 2011
Significance and Management by mutation
Prevalence and Penetrance for breast cancer genes
http://www.ambrygen.com/sites/default/files/pdfs/canc
er%20forms/BreastNext_WhitePaper_100412.pdf
If you think you can’t keep up with all this…
Don’t worry!
No one else can either!
The human brain is approaching its limit
Yet we continue to practice memory based medicine
Crane, Raymond, The Permanente Journal 7:62, 2003
Yoo et al. BMC Bioinformatics 2007 8(Suppl 9):S4
Knowledge is growing exponentially
Articles published on Breast Cancer Genetics
4335 articles in 2012
Disorders with genetic tests available
GeneTests 2014
Clinical Decision Support (CDS) •Apply Models/Guidelines to patient data
•Identify best course of action
•Results displayed as intuitive Visualizations
BRCAPRO Mutation Risk 25%
BRCAPRO Mutation Risk 25%
Consider Genetic Testing
Opposing viewpoints defined in the 1950’s
• Artificial Intelligence (AI)
– The computer would replace humans
• Intelligence amplification (IA)
– Computers have strengths and weaknesses
– Humans have strengths and weaknesses
– Humans working with computers are:
“Better...stronger...faster”
“We have the technology”
Mechanical Amplification
• Human 3 miles/hour
• Human plus bike 20 miles/hour
• Human plus car 60 miles/hour
Intelligence Amplification• Human
– Talk to patient, gather data
– Draw pedigree and eyeball
– Counsel
• Human plus computer
– Human Talk to patient, gather data
– Computer Run risk models/guidelines
– Computer Draw pedigree, visualizations
– Human Synthesize, counsel patient
High Risk Program
• Identify women at high risk• Breast imaging, Primary Care, Oncology, OB/GYN
• High Risk Clinic/System• Manage women needing
– Genetic testing
– More intensive screening
– Chemoprevention
• Risk of mutation
– BRCA testing
• Risk of developing breast cancer
– MRI
– Chemoprevention
– Personalized screening
ID High Risk
Hereditary
Hormonal
Pathologic
Risk Factors
Hereditary
Hormonal
Pathologic
Risk FactorsBreast cancer
Age diagnosed
Ovarian Cancer
Age diagnosed
Male breast cancer
Age diagnosed
Degree relative
Age all relatives
Genetic testing
Height
BMI
Parous vs nulliparous
Age first live birth
Age menarche
Age menopause
HRT years used
HRT intended use years
Combined vs estrogenNumber of biopsies
Atypical hyperplasia
LCIS
Tumor markers
ID High Risk
Eyeball
Models
Guidelines
ID High Risk
Eyeball
Models
Guidelines
Age
Vital Status Cancer statusAge diagnosis
Ethnicity/ReligionGenetic testing
Risk Factors
Eyeball
Eyeball
Multiple relatives affected
Young age at diagnosis
Multiple primary cancers
Unusual Cancer
Male breast cancer
ID High Risk
Eyeball the pedigree
Models
Guidelines
Guidelines by Examples
USPSTF for BRCA testing 2013
USPTF Ann Intern Med 2013
Guidelines by Tools
• If positive by any of the following tools
– Ontario Family History Assessment Tool
– Manchester Scoring System
– Referral Screening Tool
– Pedigree Assessment Tool
– FHS-7
Guidelines by Models
33
Women
MostHighest
risk
Current Breast Cancer Screening Guidelines:
• American Cancer Society (ACS)
• National Comprehensive Cancer Network (NCCN)
>20%
risk of
breast
cancer(Tyrer Cuzick,
BRCAPRO,
Claus)
Guidelines by Models
ID High Risk
Eyeball the pedigree
Models
Guidelines
Hereditary
Hormonal
Myriad
Pathologic
Claus
Gail
BRCAPRO
Tyrer Cuzick
Hereditary
Hormonal
Risk MutationMyriadGenetic Testing
Pathologic
Risk Mutation & Risk Breast Ca
Risk Breast CaClausChemoprevention
MRI
Personalized screening
GailChemoprevention
Personalized screening
BRCAPROGenetic Testing
Chemoprevention
MRI
Personalized
screening
Tyrer CuzickGenetic Testing
Chemoprevention
MRI
Personalized
screening
George Edward Pelham Box 1919 –2013)
British mathematician/Professor of Statistics at the University of Wisconsin
All models are wrong
George Edward Pelham Box 1919 –2013)
British mathematician/Professor of Statistics at the University of Wisconsin
All models are wrong, but some are useful
Hereditary• Breast cancer
• Age diagnosed
• Ovarian Cancer
• Age diagnosed
• Male breast cancer
• Age diagnosed
• Degree relative
• Age all relatives
• Genetic testingHormonal• Height
• BMI
• Parous vs nulliparous
• Age first live birth
• Age menarche
• Age menopause
• HRT years used
• HRT intended use years
• Combined vs estrogen
Pathologic• Number of biopsies
• Atypical hyperplasia
• LCIS
• Tumor markersBRCAPRO
BRCAPRO: Bayes-Mendel Model
Woman Vs. Machine
148 pedigrees
BRCAPRO Vs NPs and GCs
Woman Vs. Machine
You cannot have a highly trained NP or GC see every
patient
You can run risk models on every patient
Genetic Consultation
Patient Referral
Patient enters data
Risk Calculations
MRI
Options to find high risk
Clinical Decision
Support
Quick and easy risk calculations
Hughes RiskApps Express
Thru
HughesRiskApps.Com
HughesRiskApps.Com
HughesRiskApps.Com