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

Defining BRCA Genes
By Kelly Metcalfe, RN, PhD
In 1994 and 1995 respectively, the
BRCA1 and BRCA2 genes were
discovered. For women who carry
a mutation in one of these genes, the
risk of developing breast cancer is
estimated to be up to 87% by the age of
70 1 . Women with a BRCA1 or BRCA2
mutation have one of the highest known
risks for the development of breast
cancer. However, with this genetic
information, women are in a position to
be able to reduce their breast cancer risk
by using breast cancer risk prevention
strategies. Therefore, the value of
genetic testing for BRCA1 and BRCA2
mutations is that high-risk women can
be identified, and ultimately fewer
women will be diagnosed with breast
cancer and die of the disease. However,
this is all dependent on whether or
not a woman elects for a breast cancer
prevention option.
The current cancer reduction
options available to women with
a BRCA1 or BRCA2 mutation
are chemoprevention (including
Tamoxifen) 2 3 , or prophylactic surgery
(mastectomy and oophorectomy) 4 5 .
None of these options offer women
a 100% breast cancer risk reduction,
and each preventive option has
risks and benefits, both medical and
psychological. These circumstances
cause the decision-making process to
be difficult for women regarding breast
cancer prevention.
A prophylactic mastectomy involves
the removal of both breasts in the
absence of disease. The goal of
prophylactic mastectomy is to prevent
breast cancer, with its potential for
metastatic spread and potential to
cause death. Studies by Hartmann
et al. suggested that prophylactic
mastectomy offers a reduction in
risk of breast cancer of 80% or more
in women with a family history of
breast cancer 6 , and greater than an
89% risk reduction in women with a
known BRCA1 or BRCA2 mutation 4 .
Meijers-Heijboer et al. also found
that there was a significant risk
reduction of breast cancer associated
with prophylactic mastectomy when
compared to women undergoing breast
screening 5 . Research suggests that
satisfaction with the decision to have
prophylactic mastectomy is high 7 8 , and
that psychosocial functioning is not
compromised 7 9 .
In addition to an increased risk of
breast cancer, women with a BRCA1
or BRCA2 mutation also have an
increased risk of developing ovarian
cancer. The preventive removal
of the ovaries and fallopian tubes
(prophylactic oophorectomy) can
provide significant reductions in risk
of both breast and ovarian cancers
in women with a BRCA1 or BRCA2
mutation. Estimates of the effectiveness
of prophylactic oophorectomy in
preventing ovarian cancer have
varied widely from 60% to 95% 10-12 .
Prophylactic oophorectomy has also
been shown to reduce the risk of breast
cancer in women with a BRCA1 or
BRCA2 mutation. The greatest risk
reduction is observed if a woman has
a prophylactic oophorectomy prior to
the age of 40 (50% breast cancer risk
reduction) 13 . After the age of 50, no
benefit in breast cancer risk reduction
is observed. Overall, prophylactic
oophorectomy is effective at reducing
the risk of both breast and ovarian
cancers in women with a BRCA1 or
BRCA2 mutation. However, there
are important side-effects (eg. hot
flashes, vaginal dryness, decreased
libido) associated with this surgery,
as a woman is placed into immediate
menopause.
Tamoxifen is a medication that is
taken to reduce the risk of developing
breast cancer. It is a selective estrogen
receptor modulator (SERM) that
competes with estrogen for binding
to the estrogen receptor. In humans,
Dr. Kelly Metcalfe
Tamoxifen acts as an estrogen
antagonist in breast tissue, inhibiting
the growth of estrogen-dependent
breast tumors 14 . Among high-risk
women, a 49% risk reduction of
invasive breast cancer risk has
been associated with Tamoxifen 15 .
Tamoxifen usage has been shown
to reduce the risk of invasive breast
cancer by 62% in healthy BRCA2
carriers 2 . In addition, Tamoxifen
has been shown to be effective at
preventing contralateral breast cancer
(breast cancer in the opposite breast)
in both BRCA1 and BRCA2 mutation
carriers with breast cancer 3 16 . In the
National Surgical Adjuvant Breast and
Bowel Project (NSABP) P-1 Study 15 ,
which examined breast cancer risk
reduction associated with Tamoxifen
use in high-risk women, there were
medical side-effects associated with
Tamoxifen including endometrial
cancer, vascular events, and cataracts.
Making decisions about breast cancer
prevention are difficult for women.
Each option that is available to them
has benefits and risks (both medical
and psychological). No choice will
satisfy every one of an individual’s
personal objectives and no alternative
is without its risk of undesirable
outcomes. To try to help women with
these difficult decisions, we have
recently developed a decision aid for
breast cancer prevention in women
with a BRCA1 or BRCA2 mutation.
The decision aid was developed to
provide decision support to women
with a BRCA1 or BRCA2 mutation
regarding breast cancer prevention. We
are currently testing the decision aid
to determine if it is helpful for women
who have recently learned that they
6 Network News Winter/Spring 2010