Network News - Winter/Spring 2010 - Canadian Breast Cancer ...

What is BRCA?
By Dawna M. Gilchrist, MD, FRCPC, FCCMG, DHMSA
What are BRCA1 and BRCA2?
BRCA1 and BRCA2 are human genes
that belong to a class of genes known as
tumor suppressors.
In normal cells, BRCA1 and BRCA2
help ensure the stability of the cell’s
genetic material (DNA) and help
prevent uncontrolled cell growth.
Mutation of these genes has been
linked to the development of
hereditary breast and ovarian cancer.
The names BRCA1 and BRCA2 stand
for breast cancer susceptibility gene 1
and breast cancer susceptibility gene 2,
respectively.
In the general population,
approximately 1 in 8 women (12%)
will develop breast cancer and 1.5-2%
will develop ovarian cancer in her
lifetime. Only 5-10% of breast and
ovarian cancer is hereditary, that is,
due to mutations in specific cancer
susceptibility genes.
How do people know if they should
consider genetic counselling for
BRCA1 and BRCA2 mutations?
The likelihood of a harmful mutation
in BRCA1 or BRCA2 is increased with
certain familial patterns of cancer.
These patterns include the following:
For women of Ashkenazi Jewish descent:
• Any first-degree relative
diagnosed with breast or ovarian
cancer and
• Two second-degree relatives on the
same side of the family diagnosed
with breast or ovarian cancer
These family history patterns apply
to about 2% of adult women in the
general population. Women who have
none of these family history patterns
have a low probability of having a
harmful BRCA1 or BRCA2 mutation.
In a family with a history of breast
and/or ovarian cancer, it may be most
informative to first test a family member
who has breast or ovarian cancer. If
that person is found to have a harmful
BRCA1 or BRCA2 mutation, then other
family members can be tested to see if
they also have the mutation.
Regardless, women who have a
relative with a harmful BRCA1 or
BRCA2 mutation and women who
appear to be at increased risk of breast
and/or ovarian cancer because of their
family history should consider genetic
counselling to learn more about their
potential risks and about BRCA1 and
BRCA2 genetic tests.
BRCA1
Women with BRCA1 mutations have,
by age 70, an average cumulative
breast cancer risk of approximately
57% (47%-66%). Approximately half
develop breast cancer by the age of
50. By age 70, there is an average
cumulative ovarian cancer risk of
approximately 40% (35%-46%), and
this risk starts to significantly increase
in the 30’s.
Risk for Manifesting Breast Cancer
per Decade:
Age %
20-30 3.6
30-40 14.0
40-50 31.0
50-60 15.0
60-70 7.0
Men with BRCA1 mutations are only
at a slightly increased lifetime risk for
prostate cancer and breast cancer.
BRCA2
Dr. Dawna M. Gilchrist
Women with BRCA2 mutations have,
by age 70, an average cumulative
breast cancer risk of approximately
49% (40%-57%). Approximately one
in three women will develop breast
cancer by age 50. By age 70, there is an
average cumulative ovarian cancer risk
of approximately 18% (13%-23%), and
this risk starts to significantly increase
in the 40’s.
Risk for Manifesting Breast Cancer
per Decade:
Age %
20-30 0.6
30-40 12.0
40-50 36.0
50-60 20.0
60-70 36.0
Men with BRCA2 mutations are at
a three times increased lifetime risk
for prostate cancer (compared to
12% in the general population). The
lifetime risk for male breast cancer is
approximately 6%.
Risk of a Second Primary
Breast Cancer
The risk for another primary breast
cancer is up to five times higher with
a BRCA1/2 mutation (as compared to
sporadic breast cancer), with a lifetime
risk of 40-50% by age 70. The risk for a
second primary breast cancer may be
reduced by previous treatment with
Tamoxifen and/or previous treatment
with chemotherapy that produces
menopause.
Network News Winter/Spring 2010 11