Hereditary ovarian cancer

Question 1

What is the lifetime risk of breast cancer?

• BRCA1 carrier
• BRCA2 carrier

Answer 1

We quote the range of breast cancer risks in BRCA1 carriers to age 70 to be between 55 and 70 percent, and between 45 and 70 percent in BRCA2 carriers.

Question 2

What is the lifetime ovarian cancer risk?

• BRCA1 carrier
• BRCA2 carrier

Answer 2

• 40 to 45 percent for BRCA1 carriers
• 15 to 20 percent for BRCA2 carriers.

Question 3

BRCA1 carrier vs BRCA2 carrier - breast cancer characteristics?

Answer 3

• earlier onset (particularly before 50)
• higher lifetime risk of breast cancer than BRCA2
• BRCA1 carriers are more likely to develop a triple-negative breast cancer than BRCA2 carriers or those who are BRCA1/2 mutation negative
• DCIS occurs at an earlier age in BRCA1/2 carriers than in noncarriers

Question 4

Male breast cancer lifetime risk with

• BRCA1
• BRCA2

Answer 4

• risk appears to be higher with BRCA2 vs BRCA1 mutations
• In men with a BRCA2 vs BRCA1 vs no BRCA1/2 mutation, the lifetime risk of breast cancer is 7-8% vs 1% vs 0.1%

Question 5

Risk of GYN malignancies with BRCA1/2

• Fallopian tube cancer
• Primary Peritoneal Cancer
• Endometrial

Answer 5

• Fallopian tube cancer
  
  • At least 50 percent of serous cancers diagnosed in BRCA1/2 carriers are of distal fallopian tubal origin
  • Lifetime risk is 0.6% vs 0.2% (general pop)
  • May be underestimated given HGSOC may originate from FT.
• Primary peritoneal cancer
  
  • lifetime risk of 1.3 percent [prob underestimate]
• Endometrial
  
  • uterine papillary serous 1-2% in some studies; overall very low and for BRCA1 (not BRCA2) carriers

Question 6

BRCA1/2 mutations - risk in non-GYN and breast malignancies

• List the other types of cancers
• Give the associated risks

Answer 6

• BRCA1/2 mutations have higher risk of the following non-GYN/breast cancers
  
  • Pancreas
  • Prostate
  • Colorectal
  • Biliary
  • Gastric
  • Melanoma
• Associated risks
  
  • Pancreas [2 - 5x increased risk]
    
    • BRCA1 - 1%
    • BRCA2 - 5%
  • Prostate
    
    • BRCA1 - 3-4x increased risk (less defined) by age 65 ~ 9% risk
    • BRCA2 - 5-9x increased risk by age 65 ~ 33% risk
  • Colorectal - inconsistent data but BRCA1 suggests higher risk (possible 2x)
  • Melanoma - higher risk in cutaneous and uveal melanoma for BRCA2 (not BRCA1)
  • Increased risk in stomach and biliary for BRCA2 (not BRCA1)