Transcript The Surveillance and Management of Inherited Breast Cancer Risk

Shiva Sharma
SHO to Professor Redmond
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Introduction
Increased risk groups
Consideration of genetic testing
Management of patients with mutation
Follow-up
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Lifetime average risk 1 in 8
Approximately 184,450 breast cancer cases in
USA
 5-10% due to high penetrance gene carrying patients
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Breast Cancer gene first identified 1990
BRCA 1/2 mutations found to be 1 in 250-500
 Increased prevalence in some ethnic groups
Specific screening consideration given to those
classified as increased risk
 Tailored treatment options for inherited risk
groups
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Risk factor: variable increasing the chances of
developing breast cancer from the average
population
Major risk factors – double the risk
Minor risk factors – risk between 1.0-2.0
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BRCA 1/2, PTEN, Tp53
Tumour suppressor genes coding for DNA
repair
Accounts for 5-10% breast cancers
Young age of diagnosis
Aim is to recognise individuals early to reduce
morbidity/mortality
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Characteristic history
 Large number affected family
 Young age of diagnosis
 Multiple cancers in one person
 Uncommon cancers
 Common cancers at younger age
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Tumour suppressor gene
85% lifetime risk of Breast cancer
Found in 45% of families with multiple cases
 90% of families with both breast and ovarian
cancer
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Frequency 1/250-500
 More common in Ashkenazi Jewish population
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20-25% of cases where woman <30 found to
be carriers
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Major risk factors significantly increase risk
Once an major risk is identified minor factors
add little
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Average Risk – the general population
Moderate Risk – increased risk for age group,
but less than 5x
High Risk – 5-10x
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LCIS, ADH, ALH
First degree relatives without mutation
Very High Risk - >10x
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High penetrance gene mutation
Chest wall irradiation prior to 30
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Accepted national screening programs
 40 in USA
 50 in UK and Ireland
 Annual mammography and examination
 Chemoprevention not indicated
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Screening as in the average risk group
Patients should be acquainted with chemo
preventative drugs
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Annual mammography
Semi-annual breast exam
Premenopausal – Tamoxifen
Postmenopausal – Tamoxifen or raloxifene
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Woman with strong family history without
BRCA mutation
MRI with annual mammography
Screening 10years before youngest
diagnosed family member or 40
Twice yearly breast exam
Consider chemoprevention
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History of irradiation
 Annual mammography starting 5-10years after
treatment
 Annual MRI consideration
 Semi-annual exam
 Consideration for chemoprevention and risk
reduction surgery
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BRCA 1/2, PTEN, Tp53 mutations highly
penetrant genes
Genetic testing in children only for suspected
p53 mutation
BRCA mutation testing not before 25
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Guidelines for consideration of testing
Early age of onset
Multiple affected family members
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2+ relatives diagnosed <50
2+ ovarian cancer
Multiple primary cancers including breast
and ovarian in 1 patient
Male breast cancer
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Medullary and triple negative breast cancers
more likely to be BRCA
Ashkenazi Jewish descent or other ethnic
groups with known mutations
1st and 2nd degree relatives with breast
cancer
Family history prostate, thyroid sarcoma,
endometrial, adrenocortical, brain,
pancreatic cancer
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Testing for known mutations
If negative, then move on to full sequence
testing
Issue with Variation of Unknown Significance
 Recommend careful surveillance
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Careful lifetime follow-up
+/- chemoprevention
+/- risk reduction surgery
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Semi-annual exam
Annual mammography and annual MRI offset
by 6months
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Bilateral total mastectomy +/- reconstruction
95% effective
Timing of surgery should be offered to
patients in late 30’s, but before 50
Axillary SNB
 Pre-op MRI, if negative, biopsy not indicated
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Prophylactic oophorectomy
 50% reduction in Breast cancer in BRCA patients
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HRT can still be used for symptomatic relief
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Life time follow up for BRCA mutations
Gynaecology follow up with pelvic
examination annually
Continued follow-up even if prophylactic
mastectomy and oophorectomy performed
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Genetic testing is a valuable investigation
Patient interest
Informing patients
Tailored treatment and follow-up