Introduction Increased risk groupsConsideration of genetic testingManagement of patients with
mutationFollow-up
Lifetime average risk 1 in 8 Approximately 184,450 breast cancer
cases in USA 5-10% due to high penetrance gene carrying
patients 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
Risk factor: variable increasing the chances of developing breast cancer from the average population
Major risk factors – double the riskMinor risk factors – risk between 1.0-
2.0
BRCA 1/2, PTEN, Tp53Tumour suppressor genes coding for
DNA repairAccounts for 5-10% breast cancersYoung age of diagnosisAim is to recognise individuals early
to reduce morbidity/mortality
Characteristic history Large number affected family Young age of diagnosis Multiple cancers in one person Uncommon cancers Common cancers at younger age
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 Frequency 1/250-500
More common in Ashkenazi Jewish population 20-25% of cases where woman <30
found to be carriers
Major risk factors significantly increase risk
Once an major risk is identified minor factors add little
1. Average Risk – the general population2. Moderate Risk – increased risk for
age group, but less than 5x3. High Risk – 5-10x
LCIS, ADH, ALH First degree relatives without mutation
4. Very High Risk - >10x High penetrance gene mutation Chest wall irradiation prior to 30
Accepted national screening programs 40 in USA 50 in UK and Ireland Annual mammography and examination Chemoprevention not indicated
Annual mammographySemi-annual breast examPremenopausal – Tamoxifen Postmenopausal – Tamoxifen or
raloxifene
Woman with strong family history without BRCA mutation
MRI with annual mammographyScreening 10years before youngest
diagnosed family member or 40Twice yearly breast examConsider chemoprevention
History of irradiation Annual mammography starting 5-
10years after treatment Annual MRI consideration Semi-annual exam Consideration for chemoprevention and
risk reduction surgery
BRCA 1/2, PTEN, Tp53 mutations highly penetrant genes
Genetic testing in children only for suspected p53 mutation
BRCA mutation testing not before 25
Guidelines for consideration of testing
1. Early age of onset2. Multiple affected family members
2+ relatives diagnosed <50 2+ ovarian cancer
3. Multiple primary cancers including breast and ovarian in 1 patient
4. Male breast cancer
5. Medullary and triple negative breast cancers more likely to be BRCA
6. Ashkenazi Jewish descent or other ethnic groups with known mutations
7. 1st and 2nd degree relatives with breast cancer
8. Family history prostate, thyroid sarcoma, endometrial, adrenocortical, brain, pancreatic cancer
Testing for known mutations If negative, then move on to full
sequence testing Issue with Variation of Unknown
Significance Recommend careful surveillance
Bilateral total mastectomy +/- reconstruction
95% effective Timing of surgery should be offered
to patients in late 30’s, but before 50Axillary SNB
Pre-op MRI, if negative, biopsy not indicated
Prophylactic oophorectomy 50% reduction in Breast cancer in BRCA
patientsHRT can still be used for
symptomatic relief
Life time follow up for BRCA mutations
Gynaecology follow up with pelvic examination annually
Continued follow-up even if prophylactic mastectomy and oophorectomy performed