Hereditary Breast Cancer

Question 1

What is the prevalence and average age of breast carcinoma?

Answer 1

• 1 in 8 women
• Average age: mid 50s

Question 2

What are the 3 major influences of breast carcinoma?

Answer 2

3 major influences are:

• genetic changes:
  
  • * mutations affecting proto-oncogenes (HER2/Neu)
  • * tumor suppressor genes (BRCA1 and BRCA2)
• hormonal influences
• environmental variables

Question 3

What are the risk factors for **sporadic **breast carcinoma?

Answer 3

• Exposure to hormones (major risk)
• Environmental Variables
• Occur in postmenopausal women
• Overexpress estrogen receptor

Question 4

What are treatments options for a high risk breast cancer patient?

Answer 4

• Bilateral prophylactic mastectomy
• Chemoprevention (Tamoxifen)
  
  • Side effects
    
    • Venous thromboembolism
    • Endometrial cancer
    • Cataracts

Question 5

Most breast cancers are ______

Answer 5

Most breast cancers are sporadic

Question 6

**Sporadic Breast Cancer: **

• Age predilection:
• Familial incidence:

Answer 6

• Usually diagnosed after menopause
• Low incidence of cancer in the family

Question 7

What are the risk factors for sporadic breast cancer?

Answer 7

• Age
  
  • Risk increases with age
  • Median age at diagnosis is 61 years
• Hormonal factors
  
  • Early menarche/Late menopause
  • Nulliparity
  • Hormone replacement therapy
• Lifestyle
  
  • Alcohol consumption
  • Physical inactivity
  • Obesity

Question 8

What is the cause of Familial Breast Cancer?

Answer 8

MULTIFACTORIAL

• Multiple low-penetrance genes may play a role and interact with environmental triggers
• Multiple family members with cancer (“clustering”)

Question 9

• What is the main cause of hereditary breast cancer?
• How is the pedigree affected?
• What is the age predilection?

Answer 9

• Main cause is a single germline gene mutation in the family
• Multiple generations often affected
• Typically young age of breast cancer onset (

Question 10

What are the examples of hereditary breast cancers presented in class?

Answer 10

• Hereditary Breast and Ovarian Cancer (HBOC)
  
  • Ashkenazi Jewish
  • Triple negative tumors (BRCA1)
• Cowden syndrome (PTEN gene)
  
  • Breast, thyroid, uterine
• Li Fraumeni syndrome (TP53 gene)
  
  • Breast, brain, leukemia, sarcoma

Question 11

• When is first mutation present in a patient with hereditary breast cancer?
• What is the role of oncogenes and tumor suppresor genes?

Answer 11

• First mutation present in gene at conception and in germline
• Oncogenes
  
  • Accelerate cell division
  • Cancer arises when stuck in “on” mode
• Tumor suppressor genes
  
  • DNA damage response
  • Cell’s “brakes” for tumor growth
  • Cancer arises when both “brakes” fail

Question 12

Does having a gene mutation garuntee breast cancer?

Answer 12

No, it just makes it more likely

Question 13

What is the 3-2-1 rule for hereditary breast cancer?

Answer 13

Conduct further evaluation if:

• 3 family members with breast cancer regardless of age
• 2 family members with breast cancer with one being diagnosed < 50 years of age
• 1 family member with ovarian cancer

Question 14

Difference in inheritance between:

• Germline
• Somatic

Answer 14

• Germline
  
  • hereditary
  • autosomal dominant
• Somatic
  
  • acquired
  • “Two hit”

Question 15

Hereditary Breast and Ovarian Cancer (HBOC) Syndrome:

• Mutations
• Inheritance
• Associated cancers

Answer 15

• BRCA1 & BRCA2gene mutations
• Autosomal dominant inheritance
• Breast cancer
  
  • 45-85% lifetime risk
  • Risk for a 2nd primary breast cancer
• Ovarian cancer
  
  • 15-45% lifetime risk
• Other increased cancer risk
  
  • Prostate, male breast, pancreatic, melanoma, ocular melanoma