Title: Hereditary breast and ovarian cancer Who should be screened and How
1Hereditary breast and ovarian cancerWho should
be screened and How?
- Symposium on Cancer
- Waterloo Inn
- October 31, 2007
Mala Bahl, MD, MSc
2Objectives
- Describe genetic syndromes associated with breast
and ovarian cancers - Identify those at high risk for hereditary breast
or ovarian cancer - Review cancer screening and risk reduction
measures relative to the general population - Review referral opportunities for such patients
3- This presentation contains no conflicts of
interest
4General population risk
- Breast cancer
- 10.6
- 1 in 9 women
-
- Ovarian Cancer
- 1.5
- 1 in 70 women
5Breast Cancer Risk Factors
- Familial/genetic
- 1st degree relatives at 1.5-3 x risk
- Age
- Reproductive/hormonal
- Lifestyle
- Environmental
- Previous breast disease
The majority of cases have no identifiable risk
factor!
6Contribution of Family History
5-10
- 15-20 have an affected 1st/2nd degree relative
- 5 -Family history suggests high-risk gene
mutation - Majority are sporadic
15-20
7Two hit hypothesis
? age 30-50
?age 50-70
8Two hit hypothesis
? age 30-50
?age 50-70
9Familial Vs Hereditary
- Familial Clustering
- 2 ? cases in a family
- Not necessarily young cases (cases gt60 years)
- Not necessarily related cancers
- No clear pattern seen
- Shared genetics
- Shared environment
- Shared lifestyle
- Chance
10Familial Cancer
Agnes Breast 76
John 65
Mary Breast 60
Charles 74 Prostate 68
Louise d.62 Colon 59
Jean Cervical 39
Fred 41
Susan 37
Lori 33
Michael 30
11Familial Vs Hereditary
- Hereditary
- Multiple generations with same cancer
- Early onset
- gt1 cancer / individual especially in paired
organs - Pattern fits with known cancer syndrome
- Presence of rare cancers
- Most are autosomal dominant with incomplete
penetrance (like BRCA1 and 2!)
12Hereditary
Ovary, 40
Breast, 45
Ovary 50
Colon, 67
Breast,50
Breast, 35
13Factors that Influence Phenotype
- Penetrance
- Gender
- Co-morbidites
- Lifestyle
- Environment
- Modifier genes
- Risk-Reduction
14Causes of Hereditary Breast Cancer
of Hereditary Breast Cancer 2040 1030 lt1
lt1 lt1 3070
Gene BRCA1 BRCA2 TP53 Li-Fraumenni PTEN
Cowdens CHEK2 Undiscovered genes
BOCS
ASCO
15Breast and Ovarian Cancer Syndrome
- Refers to BRCA1 or BRCA2
- AD inheritance
- Tumor Suppressors- a caretaker function
- 1 in 800 women in the general population
-
- BRCA1 identified in 1994
- gt600 mutations
- BRCA2 in 1995
- 450 mutations
16Founder mutations
- 4 founder mutations among Ashkenazi Jews
- Prevalence 1 in 40
- Other groups with BRCA!/2 mutation families
- French-Canadian
- Mennonite
- Icelandic
- Scandinavian
- Irish
- British
- Dutch
- Japanese
- Pakistani
17Hereditary Breast and Ovarian Cancer BRCA1
Breast cancer 85
Second primary breast cancer 40-60
Ovarian cancer 20-40
- Breast ca risk by age 50 50
- Risk for Male Breast Cancer Unclear
- ?Risk for Prostate Cancer if lt 65
Adapted from ASCO
18Hereditary Breast and Ovarian Cancer BRCA2
breast cancer (30-85)
male breast cancer (6.7)
ovarian cancer (10-20)
- prostate cancer(12-18)
- melanoma (?2.5x)
- bile duct (5x), pancreas ca (5)
Adapted from ASCO
19Clues to Breast/Ovarian Ca Syndrome
- Breast Cancer lt age 35
- ? 2 cases Breast ca before age 50
- Bilateral breast cancer, first lt50
- Serous ovarian cancer
- Breast and ovarian cancer in the same woman
- Male breast cancer
- Ashkenazi Jewish heritage with breast cancer
ASCO
20More Breast Cancer Syndromes (lt1)
- Cowdens 25-50 breast ca risk
- Oral lesions, GI hamartomas, benign breast dz
- Thyroid, uterine lesions or CA, macrocephaly
- Li-Fraumeni breast ca lt age 40
- Often childhood cancers
- sarcoma, leukemia, brain adrenocortical CA
- Peutz-Jeghers - lt1
- Childhood GI hamartomas, colon CA
- Pigmentation of lips, buccal mucosa, hands/feet
21Clinical Management Options
- Screening and other interventions
22Who needs what?
Assessment
Intervention
Risk
Standard prevention recommendations
Average
Family History
Personalized prevention recommendations
Moderate (Familial)
Referral for genetic evaluation
High (Genetic)
23Ontario Screening Guidelinesfor the general
population
- Breast
- Mammogram every 1-2 years from 50
- Annual clinical breast exam for all women
- Monthly breast self exam for all women
- No guidelines for men
- Ovary
- No gen population screening guidelines
24Moderate Risk Families
- Low risk of BRCA1/ 2 or other cancer syndromes
- Lifetime risk 10-30
- Screening recommendations
- BSE monthly CBE once or twice a year
- Annual (digital) mammo from 40 or 5-10 yrs prior
to youngest cancer - Immediate biopsy of any suspicious findings
- Explore Chemoprevention
- Lifestyle modifications
25Lifestyle Modification
- Good for all risk categories!
- Exercise 30 min. or more most days
- Weight control
- Diet ??
- Less saturated/trans fat
- Less refined flour, sugar
- More fruits/vegetables, whole grains, legumes
- Alcohol less than 1-2 drinks/day
- Breast feeding
26Options for High Risk Patients
- Increased surveillance
- Prophylactic surgery
- Lifestyle changes
- Chemo prevention
27Surveillance BRCA1/2
- Breast
- Annual mammogram from age 30 (digital)
- Annual Breast MRI from 30
- CBE q6-12mos from age 18
- Monthly breast self exam from age 18
- Ovarian screening significant limitations
- Ca-125, TV ultrasound 1-2/yr- age 25-35
- Suboptimal early detection
- high false positive
- Preferred in a research setting
Class I
Class B
Class E
28Other
- Heightened male breast screening
- Chest wall exams, visual
- Consider PSA at age 40
- Monitor skin and general health
- Pancreatic screening research (BRCA2)
29Challenges to Surveillance
- CBE detects few cancers missed by above
- Promotes awareness no ? mortality
- Mammo
- insensitive in younger patients 26-42
- MRI
- Sensitivity 83-100
- Lower specificity
- TV US
- FH, Sensitivity 92, Specificity 97.8
- PPV 11 if ? 2 cases, PPV20
- CA 125 Sensitivity 35-55
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31Series of 3991 high-risk pts
- 155 cancers
- 78 of cancers detected by MRI
- 38 by mammo
- 18 (10 DCIS, 8 invasive) on mammo NOT MRI
- 42 by US (lt1 detected by US only)
- Interval cancer lt 10 if MRI
- Of MRI detected cancers
- 12-27 DCIS
- if invasive ca 75-94 lt 2 cm
- Axillary node mets seen in 17-25
32Other Management Options BRCA1/2
- Mastectomy
- Cohort shows ?96 breast ca
- Total Mastectomy, no node dissection
- Path review- cancer found in 7
- Oophorectomy
- ? ovarian ca 85
- ?Breast ca by 50-66
- Birth Control Pill
- Tamoxifen
33Your Role
- Detailed family history
- Cancer status in 1st and 2nd degree relatives
- Type of primary cancer(s) in each relative
- Age of disease onset
- Cancer status in both sides of the family
- Ethnic background on both sides
- Other medical findings benign tumors, etc.
34Referral opportunities
Referral forms available at our
website www.grandriverhospital.on.ca follow
links to GRRCC, then Treatments Services then
Genetic Counseling Service
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