Shiva SharmaSHO to Professor Redmond

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

Screening as in the average risk group

Patients should be acquainted with chemo preventative drugs

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

Careful lifetime follow-up+/- chemoprevention+/- risk reduction surgery

Semi-annual examAnnual mammography and annual

MRI offset by 6months

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

Genetic testing is a valuable investigation

Patient interest Informing patients Tailored treatment and follow-up