Breast Cancer Risk and Risk Assessment Models

1
Breast Cancer Risk and Risk Assessment Models

• Jessica Ray, MS, CGC
• Cancer Genetic Counselor
• Ambry Genetic Laboratories
• jray_at_ambrygen.com

Vida! Educational Series - Promoting Good
Health
2
Learning Objectives

• Identify Personal and Family Characteristics that
  may indicate an inherited increased risk for
  cancer
• Understand the role of genetic counseling in
  assessing patients with possible hereditary
  cancer syndromes
• Understand characteristics, advantages,
  limitations, and differences of the Gail and
  BRCAPRO risk-assessment tools used by clinicians
  to help establish cancer risk

3
(No Transcript)
4
Who Is at High Risk?

• Atypia
• 5-year Gail risk gt1.7
• 2 or more 2nd-degree premenopausal affected
  relatives
• Combined estrogen-progesterone hormone therapy
  for more than 10 years
• Mammographically dense breasts
• Obesity

5
Who Is at Very High Risk?

• Personal history of BC lt50
• BRCA1 or BRCA2 mutation carrier
• 2 or more 1st-degree relatives with BC
• Lobular carcinoma in situ (LCIS)
• Atypia and a 1st-degree relative with BC

6
What is Genetic Counseling?

• Genetic Counseling is a communication
  process that deals with both the medical and
  psychological issues associated with the
  occurrence of a genetic disorder in a family
• Cancer genetic counseling focuses on hereditary
  cancer syndromes
• This process involves one or more trained
  professionals to help the individual or family

7
Reasons for Seeking Genetics Consultation

• To learn about
• Personal risk for cancer
• Childrens risk for cancer
• Familys risk for cancer
• Risks for developing cancer if you have a cancer
  gene
• Recommendations for screening, surveillance,
  and/or treatment
• Educational information
• To obtain genetic DNA testing

J Med Genet 2000 37866-874
8
(No Transcript)
9
(No Transcript)
10
Key Flags that Warrant Genetic Counseling

• Significant family medical history-breast,
  ovarian, prostate, colon, uterine, melanoma,
  pancreatic, or other cancers
• Cancer occurs in every generation
• Early age of onset (lt 50 years)
• Male breast cancer
• Bilateral cancer, or multiple primary cancers in
  one individual
• Known family genetic mutation
• Ethnicity Ashkenazi Jewish ancestry

11
Sporadic, Familial or Hereditary?

• 5-10 cancers have a hereditary component
• Over 200 hereditary cancer syndromes described
• Hereditary cancer tends to occur at younger ages
  than sporadic cancer, often bilateral, multifocal
• Lifetime risks of cancer exceed cancer risks due
  to noninherited factors (early menarche,
  nulliparity, late age of menopause, HRT, etc)
• Majority show an autosomal dominant inheritance
  pattern (few are recessive)

12
(No Transcript)
13
(No Transcript)
14
Average Age of Diagnosis Hereditary
Sporadic

• Breast 62
• Ovarian 60
• Prostate 71

• Breast 41
• Ovarian 40-50
• Prostate 63

15
(No Transcript)
16
(No Transcript)
17
(No Transcript)
18
(No Transcript)
19
(No Transcript)
20
Gail Model
National Cancer Institute http//www.cancer.gov/b
crisktool/Default.aspx
21
(No Transcript)
22
(No Transcript)
23
(No Transcript)
24
Gail Model Advantages

• Identifies women who could benefit from
  preventive interventions may assist in making
  clinical decisions (Determination of eligibility
  for tamoxifen for breast cancer risk
  reductionGail scoregt1.7)
• Incorporates risk factors other than family
  history (eg, reproductive variables, atypical
  hyperplasia, history of breast biopsies)
• Calculation of breast cancer risk in absence of
  family history in women
• Shows that BC risk increases with age and,
  therefore, may prompt discussion about the
  importance of BC screening
• Used to counsel and educate women, especially
  those who overestimate their BC risk

25
Gail Model Limitations

• Not validated for black, Hispanic, and other
  ethnic groups
• Only solicits family history involving
  first-degree relatives
• May underestimate risk when family history is on
  fathers side
• Does not take into account age at which relatives
  developed BC
• Effect of number of breast biopsies (without
  atypical hyperplasia) may cause inflated risk
  estimates
• May underestimate risk for women with
  demonstrated mutations of the BRCA1 or BRCA2 genes

26
(No Transcript)
27
BRCAPRO - Advantages

• Incorporates both affected and unaffected family
  members in estimation of carrier probability
• incorporates maternal and paternal breast and
  ovarian cancer history
• age at cancer diagnosis, current ages, ages
  relatives became deceased considered
• Ashkenazi Jewish ethnicity taken into
  consideration
• Oophorectomy status and breast cancer receptor
  status considered

28
BRCAPRO - Limitations

• Dependent on published estimates of prevalence
  and penetrance of BRCA1 and BRCA2
• Does not consider more distant family history
  past 1st and 2nd degree relatives
• Does not consider other potential susceptibility
  genes with features similar to BRCA1 and BRCA2

29
When Do You Offer Testing?

• American Society of Clinical Oncology recommends
  genetic testing
• The individual has a personal or family history
  of features suggestive of a genetic cancer
  susceptibility condition
• The test can be adequately interpreted
• The results will aid in diagnosis or influence
  the medical or surgical management of the
  patient or family members at hereditary risk of
  cancer
• ASCO recommendations
• Genetic testing only be done in the setting of
  pre-and post-test counseling,
• Should discuss possible risks and benefits of
  cancer early detection and prevention modalities

30
Implications/Important Points

• What do we offer individuals at high risk for
  hereditary cancers who test negative for a
  genetic mutation?
• Negative genetic test result does not mean No
  Increased Risk!!
• AZCC High Risk Clinic for individuals at greater
  risk of developing cancer
• Must continue studies to find other genes
  responsible for hereditary cancers
• Must develop more advanced, individualized risk
  assessment tools