Familial Breast Cancer

1
Familial Breast Cancer

• Maira Kentwell
• Associate Genetic Counsellor
• Familial Cancer Centre
• Royal Melbourne Hospital

2
What is the Familial Cancer Centre

• Provides an assessment of family history of
  cancer to
• Educate individuals regarding risks of developing
  cancer
• Provide information regarding risk management
  options
• Provides information regarding genetic testing
• Provides counselling and support through-out
  process
• Staff
• Genetic Counsellors, Clinical Geneticists,
  Genetics Fellows, Medical Oncologists, Breast
  surgeons, Gastroenterologists, Research staff

3
Genetic Counsellors

• Role of Genetic Counsellors
• Gather information regarding family history and
  verify cancers
• Provide the education regarding risk assessment,
  genetics and components to genetic testing
• Provide support and counselling to individuals
  through out process
• Research

4
Role of Genetic Counsellor

• Assessment
• Interpretation of family and medical histories to
  assess the chance of disease occurrence or
  recurrence
• Provision of information
• Education about inheritance, testing, management,
  prevention, resources and research
• Counselling
• promote informed choices and adaption to the risk
  or condition
• assess clients own perception and interpretation
  of the family history
• explore clients response to the information
• Co-counselling with clinical team (risk
  management advice)
• Pre-natal, Cancer, Neuro (HD), Cystic Fibrosis,
  General paediatrics adult

5
Referrals to FCC

• Self-referral
• Approached by relative
• Clinician referral
• Other health professionals
• Research participant

6
The Patient Journey

• Collecting a family history
• Risk assessment
• Likelihood of a hereditary cancer syndrome
  (family assessment)
• Ave, moderate, high risk (individual cancer risk)
• Risk management advice
• Genetic testing (if available) pre post test
  counselling
• Follow up

7
Collecting a family history

• 3 generation pedigree
• Affected / unaffected
• Ages types of cancer diagnosis
• Face to face interview or Questionnaire
• Verification
• cancer registry
• consent, death certificates

8
Initial referral
9
Collecting a 3 generation pedigree
Stomach ca
10
Collecting a 3 generation pedigree
ovarian ca
11
Risk categories

• Low (average risk / population risk)
• Moderate
• Potentially High
• Families with a hereditary cancer syndrome
• BRCA1/2
• BRCAX
• Rare syndromes
• - Cowdens syndrome, p53

12
How common is hereditary breast
cancer?

Hereditary breast
Family
cancer genes
history
Most breast cancer
13
Low risk

• At or slightly above average risk
• No personal of family history of breast ca
• One 1st degree relative diagnosed with breast
  cancer at age 50 or older
• One 2nd degree relative diagnosed with breast
  cancer at any age
• Two 2nd degree relatives on the same side of the
  family diagnosed with breast cancer at age 50 or
  older
• Two 1st or 2nd degree relatives diagnosed with
  breast cancer at age 50 or older, but on
  different sides of the family
• BreastScreen from 50, or eligible starting 40

14
Moderate risk

• One 1st degree relative with breast cancer before
  50
• Two 1st or 2nd degree relatives on same side of
  family with breast cancer
• Two 2nd degree relatives on same side of family
  diagnosed with breast cancer, at least one before
  age 50
• ALL WITHOUT HIGH RISK FEATURES
• BreastScreen
• Additional surveillance from younger age and /or
  increased frequency recommended on individual
  basis

15
Moderate risk

• Multi-factorial
• Combination of genes and environment
• Moderate risk breast cancer genes
• Lifestyle factors

16
Moderate risk
I
Breast cancer dx 60 yrs
II
Breast cancer dx 48 yrs
III
40
IV
17
Psychological issues to consider

• Concern is predominantly for themselves
• fear of developing cancer
• perceived risk - overestimate
• subjective - often based on experience with
  cancer (family story)
• age at dx of cancers
• womans current age
• relationship/role with affected individuals

18
Genetic Counselling moderate risk

• Expand pedigree
• Explore psychological issues (risk
  perception/anxiety)
• Education / information
• High risk breast cancer susceptibility gene
  rare/unlikely
• Breast cancer common condition
• Personal breast cancer risk increased, more
  likely will not develop breast cancer
• Breast cancer on both sides of family does not
  have additive effect
• Uncertainty

19
High Risk Features

• 2 or more relatives on same side of family with
  breast or ovarian cancer plus
• Breast cancer diagnosed under 40
• Bilateral breast cancer
• Male breast cancer
• Jewish Ancestry
• Breast and ovarian cancer at any age in the same
  woman
• A third family member with breast or ovarian
  cancer

20
S family
21
High risk Genetic testing for breast cancer

• BRCA1/2 account for less than 5 of inherited
  breast cancers
• Tumour suppressor genes (protect against
  breast/ovarian cancer)
• Present in men and women
• Brca/ovca susceptibility if mutation present
• Autosomal dominant inheritance
• Incomplete penetrance
• BRCAX

22
Genetic testing process

• Blood sample consent required from living
  affected individual
• DNA storage possible
• Mutation searching
• Variety of methods
• Not able to detect all mutations
• Genetic Counselling
• - Informed consent
• - Pros cons of genetic testing
• - Anticipatory guidance
• - Exploring family communication

23
S family
24
Genetic testing

• No mutation detected in BRCA1/2
• inconclusive / uninformative
• assessment falls back on family history
• no predictive testing available
• Mutation detected in BRCA1/2
• Future cancer risks
• Predictive testing for relatives

25
S family
26
Implications of genetic testing

• Psychological implications - guilt, blame
• Implications for own health
• Implications for other family members
• Disclosure to other family members
• Testing of children

27
Assessment for genetic testing

• Likelihood of known gene mutation?
• Likelihood not yet discovered gene?
• 1. Family history
• 2. Calculation models
• 3. Clinical meeting

28
Assessment for BRCA1/2 mutation other factors

• Pathology
• Grade 3 ERPR-ve, medullary breast cancer
• Epithelial ovarian cancer
• Family size
• Adopted, small, age of death
• Family gender
• Number of men and women
• Other cancers
• Prostate and pancreatic cancer
• Ancestry
• Ashkenazi Jewish ancestry
• Dutch, Eastern European

29
Rapid Genetic Testing

• Woman with newly diagnosed breast cancer
• Rapid genetic testing
• (approx 1-2 weeks)
• Treatment decision making
• Mastectomy/bilateral mastectomy
• Lumpectomy radiotherapy

30
Risk Management Options

• Medical staff
• Surveillance
• Risk reduction surgery
• Chemoprevention

31
Li-Fraumeni Syndrome

• Tumour suppressor gene (p53)
• Autosomal dominant inheritance
• Almost 100 lifetime risk for development of
  cancer
• Multiple cancer types
• Breast cancer, bonesoft tissue sarcomas, brain
  tumours, adrenocortical cancer
• Cancer occurring in childhood
• Very rare

32
Summary

• For most people, having a family history of
  cancer will not alter their personal risk of
  developing the disease
• To have an inherited a single gene which gives
  a predisposition to develop cancer is very
  uncommon
• Responding to queries regarding family history
  of cancer
• refer to FCC
• (RMH, MMC, GHSV, PMCC, Cabrini)
• discuss with Genetic Counsellor

33
Familial Breast Cancer

• Maira Kentwell
• Associate Genetic Counsellor
• Familial Cancer Centre
• Royal Melbourne Hospital/Western General Hospital
• Referrals 9342 7151