Cancer models

Question 1

What does the Gail Model estimate and what

factors are included in this risk model?

Answer 1

The Gail Model provides two risk estimates:

Absolute lifetime risk of breast cancer to age 90 years
Five year breast cancer risk

Factors include:
   Age
   Age at menarche
   Age at first live birth
   Number of first-degree relatives with breast cancer
   Ever had a breast biopsy
   Number of breast biopsies
   Presence of atypical hyperplasia
   Race

Question 2

What factors are not included in the Gail Model

and when is it inappropriate to use this model?

Answer 2

Factors that are not included in the Gail Model:
   Other cancers (ex. ovarian cancer)
   Second-degree relatives
   Paternal history
   Age at cancer diagnosis in relatives

It is inappropriate to use the Gail Model if there is significant history of any of the above factors, or if a woman has previously had DCIS, LCIS, or a
diagnosis of breast cancer.

DCIS, LCIS, or breast cancer are more significant risk factors than any element included in the Gail Modelß

Question 3

What does the Claus Model estimate and how are

the risk tables in this model effectively used?

Answer 3

The Claus Model estimates cumulative breast cancer risk based on family history alone.
Designed for selection of a Claus Table representing the age of a patient at the time of a breast cancer diagnosis and the age of a relative at the time of a breast cancer diagnosis

To effectively using the Claus Model tables (aka, “fudging”), approximate the degree of genetic relationship (FDR or SDR) to a patient.

Examples:

• no mother-maternal grandmother relationship use mother-maternal aunt relationship
• no sister-maternal aunt relationship use mother-maternal aunt relationship

Question 4

Identify the prior probability risk models

and what they are designed to estimate.

Answer 4

Prior Probability Models

Bayes Mendel (BRCAPro, MMRPro, PancPro)
 -uses cancer family history and age at diagnosis to determine the likelihood that an individual will test positive for a mutation 

Myriad Prevalence Tables
-uses features of a family compared to a table that provides a risk figure of how often a mutation was found in such a family

Penn II Model
-uses information about known risk factors (similar to Gail Model) to calculate the likelihood that a mutation will be found

Tyrer-Cuzick
-uses Gail Model-type information and family history of breast findings to calculate the likelihood that a mutation will be found

BOADICEA
-similar to Bayes Mendel

Question 5

What percentage of ovarian cancers are

sporadic versus hereditary?

Answer 5

Ovarian Cancer
Sporadic  =  ~90%
Hereditary  =  5-10%
-Caused by mutations in a single gene
-Highly penetrant

Question 6

Gail Model

Answer 6

●For breast cancer risk only
oCannot be used for an already affected proband
●Considers previous biopsy hx (was ADH seen?)
●Considers current age, age at first menses, age at first live birth
●Only takes into account 1st degree female relatives with breast cancer
●Doesn’t take into account male breast cancer, ovarian cancer, age of onset of cancers, any paternal hx
●Tends to underestimate risk

Question 7

Claus Model

Answer 7

●For breast cancer risk only
oCannot be used for an already affected proband
●Considers current age
●Considers first and second degree relatives with breast cancer and age at dx
●Doesn’t take into account male breast cancer, ovarian cancer, personal reproductive hx, or biopsy hx
●Tends to underestimate risk

Question 8

BRCAPro

Answer 8

●For breast cancer AND mutation risk
●Considers current age, age of breast cancer dx, bilateral breast dx, first and second degree relatives with breast or ovarian cancer, male breast cancer, and age of dx in relatives
●Doesn’t take into account personal reproductive hx or biopsy hx
●Tends to underestimate risk

Question 9

Tyrer-Cuzick

Answer 9

●For breast cancer AND mutation risk
oConsiders risk for “lower penetrance” gene in addition to BRCA
●Consdiers current age, age of breast cancer dx, bilateral breast dx, BMI, personal reproductive hx (including age at menopause which is not considered by Gail), HRT use, breast bx hx (was ADH or LCIS seen), first and second degree relatives with breast or ovarian cancer, and age of dx in relatives
●Doesn’t take into account male breast cancer
●Tends to overestimate risk

Question 10

BOADICEA

Answer 10

●For breast cancer AND mutation risk
●Takes into account personal and family hx of breast, ovarian, pancreatic cancer, and male breast and prostate cancer.
●Considers breast cancer pathology
●Doesn’t take into account personal reproductive hx (age at menses, age at menopause, age at first live birth)
●Considers previous negative/positive genetic testing
●Pedigree entry tool, very time consuming
●Fairly accurate risk assessment but time consuming