Hereditary Breast Cancer

Question 1

Where is BRCA gene 1 located? What are it’s genetic characteristics?

Answer 1

Chromosome 17 long arm
Autosomal dominant
High penetrance

Question 2

Where is the BRCA 2 gene located?

Answer 2

Chromosome 13 long arm

Question 3

Lifetime cancer risks in patients with BRCA 1

Answer 3

• Breast 74%
• Ovarian 44%
• Poor prognosis for breast cancers (triple negative, high histological grade)
• Rise in incidence in early adulthood

Question 4

Lifetime cancer risks in patients with BRCA 2

Answer 4

• Breast 69%
• Ovarian 17%
• Higher risk in males
• Associated with more pancreatic cancer, prostatic cancer, malignant melanoma

Question 5

Suspicion for BRCA gene carrier

Answer 5

• One 1st degree relative with breast cancer before 40 year old
• Two first / second degree relatives with breast cancer < 60 year old
• Three or more first /second degree relatives with breast cancer at any age
• Close relative with bilateral cancer breast
• Male breast cancer

Question 6

Management of BRCA carriers

Answer 6

• Modifiable lifestyle choices
  
  • Avoid smoking
  • Avoid OCP
  • Age of first birth
  • Breast feeding
• Reproduction counselling
• Risk reduction surgery
  
  • Prophylactic bilateral mastectomy
  • Bilateral salpingo-oophorectomy

Question 7

Breast surveillance for BRCA carriers

Answer 7

• CBE every 6 months from age of 18
• MRI breast from age of 25
• MMG from age of 30

Question 8

Ovarian surveillance for BRCA carriers

Answer 8

Transvaginal USG + CA 125 every 6 months from 30 years old or 5-10 years before first diagnosis of ovarian cancer in family

Question 9

Evidence for chemoprevention in BRCA

Answer 9

NSABP P-1 trial

• P: BRCA 1 and 2 carriers with no breast cancer diagnosis
• I: tamoxifen
• Result: reduced breast cancer risk in BRCA 2 not BRCA 1

Question 10

Reproduction counselling

Answer 10

50% children will carry cancer-predisposition variant

Question 11

Indications for genetic testing

Answer 11

• Young breast cancer diagnosed < 45
• Strong family history
• Multiple primary breast cancer
• Triple negative breast cancer
• Invasive lobular cancer with family hx of diffuse gastric cancer
• Male breast cancer
• Exocrine pancreatic cancer, any age
• Metastatic prostate caner, intraductal/cribiform

Question 12

Other cancers associated with BRCA 2

Answer 12

• Ovarian
• Pancreatic
• Malignant Melanoma
• Prostate