risk assessment, genetics, and prevention · 5/3/2016 · risk assessment, genetics, and...
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May 3, 2016 1
Risk Assessment,
Genetics, and Prevention
Katherine D. Crew, MD MS
Director, Clinical Breast Cancer
Prevention Program
Columbia University Medical Center
Outline
Breast cancer risk factors
Hereditary breast cancer genes (BRCA1/2)
Benign breast disease
Risk-reducing strategies
Breast cancer risk assessment in primary
care
2 May 3, 2016
Case #1
A 32-year-old premenopausal
woman of Ashkenazi Jewish
descent has a strong family
history of breast and ovarian
cancer. Her mother has a
positive BRCA2 mutation
(6174delT). She had
menarche at age 14 and her
first child at age 25. She
denies OCP use or any
breast complaints.
3 May 3, 2016
Age1
Stomach
cancer
MBC 70
OC 59
BC 60
BRCA2+
BC 20
BC 50s BC 40s
BC 80s
AJ AJ
BRCA2+
Age 32
Age 8
Breast Cancer Risk Factors
5 May 3, 2016
BRCA1/BRCA2 mutations
Account for 2-7% of breast cancers, 10-
15% of ovarian cancers
Prevalence is 1:400 in the general
population, 1:40 in Ashkenazi Jews
Lifetime risk of breast cancer 40-60%,
ovarian cancer 20-40%
6 May 3, 2016
Pai Cancer 2005
Nelson Ann Intern Med 2005
Risch JNCI 2006
Chen JCO 2007
Red Flags for Hereditary Breast and
Ovarian Cancer (HBOC) Syndrome
7 May 3, 2016
NCCN USPSTF
Ovarian cancer
Breast cancer, age<45
Bilateral breast cancer
Triple negative breast cancer,
age<60
Male breast cancer
Pancreatic cancer with additional
HBOC-associated cancer
Ashkenazi Jewish anscenstry with
HBOC-associated cancer
Previously identified BRCA
mutation in the family
Non-Ashkenazi Jewish: 2 first-degree relatives with breast
cancer, 1 diagnosed at age<50
3 or more first/second-degree relatives
with breast cancer
2 or more first/second-degree relatives
with ovarian cancer
Both breast/ovarian cancer among
first/second-degree relatives
First-degree relative with bilateral
breast cancer
Male relative with breast cancer
Ashkenazi Jewish: any
first/second-degree relatives with
breast or ovarian cancer
www.nccn.org
USPSTF Ann Intern Med 2005
Bellcross CEBP 2013
Possible Genetic Test Results
8 May 3, 2016
Family member’s
test results
Your test result Your risk
stratification
Informative positive - BRCA +
Informative negative BRCA + BRCA -
Uninformative
negative* No known mutation BRCA -
Variant of Uncertain
Significance* No known mutation VUS
* Testing a family member affected by cancer may help to further define your risk.
HIGH
RISK
AVERAGE
RISK
MODERATE
RISK
MODERATE
RISK
Cancer Risk among
BRCA Mutation Carriers
9 May 3, 2016
Struewing NEJM 1997
Liede JCO 2004
Tai JNCI 2007
Evans J Med Gen 2010
NCI (SEER) 2012
Risk Management:
Intensive Screening
10 May 3, 2016
PROCEDURE AGE TO BEGIN FREQUENCY
Breast cancer Self breast exam 18 years Monthly
Clinical breast
exam 25 years
Every 6-12
months
Mammography 25 years Yearly
Breast MRI 25 years Yearly
Ovarian cancer Pelvic exam 30 years
(no BSO) Every 6 months
Transvaginal USG
and CA-125
30 years
(no BSO) Every 6 months
www.nccn.org
Surgical Management:
Risk-Reducing Surgeries
11 May 3, 2016
Hartmann JNCI 2001
Kauff NEJM 2002
Rebbeck NEJM 2002
Rebbeck JCO 2004
Finch JAMA 2006
Rebbeck JNCI 2009
Domchek JAMA 2010
Finch JCO 2014
Ca
nc
er
Ris
k R
ed
uc
tio
n (
%)
12 May 3, 2016
Easton NEJM 2015
Case #2
A 63-year-old Hispanic postmenopausal
woman has a screening mammogram with
heterogeneously dense breasts and new
calcifications in the right breast. Core
breast biopsy and subsequent excisional
biopsy revealed atypical ductal hyperplasia.
Her age of menarche was 12 and she has
2 children with her first delivery at 35. She
has no family history of breast cancer.
According to the Gail model, her 5-year risk
of invasive breast cancer is 3.2% and
lifetime risk is 14.1%.
13 May 3, 2016
Spectrum of Benign Breast Disease
15 May 3, 2016 Dupont & Page NEJM 1985
Lopez-Garcia Histopathology 2010
Non-proliferative lesions Proliferative lesions w/o atypia ADH DCIS IDC
LOBULAR NEOPLASIA
Low grade DCIS
Intermediate grade DCIS
High grade DCIS
RR 10.0
Epithelial hyperplasia
Intraductal papilloma
Sclerosing adenosis
Radial scar
RR 1.5-2.0
Mild ADH
Moderate ADH
Severe ADH
Borderline lesion
RR 4.0-5.0
16
Estimating Breast Cancer Risk:
Gail Model
Age 45
Race Hispanic
Age of first menstrual period 13
Age of first live birth 30
Number of first-degree relatives with
breast cancer 1
Number of breast biopsies 1
Presence of atypical cells Yes
www.cancer.gov/bcrisktool 5-Year Risk = 3.6%
Lifetime Risk = 28.6%
May 3, 2016
Medical Management: Antiestrogens
for breast cancer prevention
17 May 3, 2016
Exemestane
Anastrozole
Selective estrogen receptor
modulators (SERM)
Raloxifene
Risks and Benefits of Tamoxifen
for Chemoprevention
18 May 3, 2016
Fisher JNCI 2005
Rate
per
1000
RISKS BENEFITS
*P<0.05
* *
*
*
Risks and Benefits of Tamoxifen
for Chemoprevention
19 May 3, 2016
Fisher JNCI 2005
Rate
per
1000
RISKS BENEFITS
*P<0.05 *
Long-Term Follow-Up with
Tamoxifen for Chemoprevention
20 May 3, 2016
Cuzick Lancet Oncol 2015
Tota
l # o
f C
ases
Endometrial Cancer
*P<0.05
*
Breast Cancer
*
* Median follow-up of 16 yrs
Tamoxifen vs. Raloxifene for
Chemoprevention
21 May 3, 2016
Vogel Cancer Prev Res 2010
Rate
per
1000
RISKS BENEFITS
*P<0.05
* *
*
*
Risks and Benefits of Aromatase
Inhibitors for Chemoprevention
22 May 3, 2016
Tota
l # o
f C
ases
*P<0.05 Median follow-up of 5 yrs
*
Tota
l # o
f C
ases
Median follow-up of 35 mo
* *
Goss NEJM 2011
Cuzick Lancet 2014
23
Premenopausal Postmenopausal
No SERM
Risk Assessment
Hysterectomy
osteoporosis Exemestane or
Anastrozole >
Raloxifene
Uterus intact
No osteoporosis Tamoxifen
History of
blood clots
Tamoxifen >
Raloxifene
Choice of Chemopreventive Agent
Raloxifene >
Tamoxifen
Uterus intact
osteoporosis
May 3, 2016
24 May 3, 2016
Integration into Clinic Workflow
PATIENTS: RealRisks decision aid
PROVIDERS: BNAV tool
Genetics Clinic: Pre/post-test genetic
counseling
Mammography:
Avon Breast Imaging Tablet-based survey
Breast Clinic: Screening, Risk-reducing
surgeries, Chemoprevention,
Lifestyle modification
Primary Care Clinic:
ACN/clinics BNAV alert
Reinforce health behaviors
made by specialist High-risk alert
to PCP
Facilitate shared decision
making with patient
High-risk women
referred to DA Facilitate shared decision
making with specialist
Facilitate shared decision
making with PCP
RealRisks decision aid
25 May 3, 2016
RealRisks decision aid
26 May 3, 2016
Narrative of Rose
27 May 3, 2016
Chemoprevention Module
28 May 3, 2016
Chemoprevention Module
29 May 3, 2016
Interactive Games
30 May 3, 2016
Eliciting Patient Preferences
31 May 3, 2016
Action Plan
32 May 3, 2016
BNAV Toolbox for PCPs
33 May 3, 2016
Chemoprevention Toolbox
34 May 3, 2016
Learning Objectives with Slide Presentation
35 May 3, 2016
Videos of Expert Opinions
36 May 3, 2016
Case-Based Learning
37 May 3, 2016
References
38 May 3, 2016
39
Summary
Recent increase in breast cancer incidence,
but decreasing mortality due to screening and
better treatments
Expanding options for risk-appropriate breast
cancer prevention strategies
Under-utilization of genetic testing and
chemoprevention
Breast cancer is preventable!
May 3, 2016
INTERESTED IN LEARNING MORE ABOUT
HOW TO REDUCE BREAST CANCER RISK?
40 May 3, 2016