OVERVIEW
Information
about the prevention of cancer and
the science of screening appropriate
individuals at high-risk of
developing cancer is gaining
interest. Physicians and individuals
alike recognize that the best
"treatment" of cancer is preventing
its occurrence in the first place or
detecting it early when it may be
most treatable.
Breast cancer
is the second leading cause of
cancer death in women in the United
States, with approximately 200,000
cases diagnosed each year. Progress
in the areas of screening and
treatment may allow for earlier
detection and higher cure rates.
The chance of an individual
developing cancer depends on both
genetic and non-genetic factors. A
genetic factor is an inherited,
unchangeable trait, while a
non-genetic factor is a variable in
a person's environment, which can
often be changed. Non-genetic
factors may include diet, exercise,
or exposure to other substances
present in our surroundings. These
non-genetic factors are often
referred to as environmental
factors. Some non-genetic factors
play a role in facilitating the
process of healthy cells turning
cancerous (i.e. the correlation
between smoking and lung cancer)
while other cancers have no known
environmental correlation but are
known to have a genetic
predisposition. A genetic
predisposition means that a person
may be at higher risk for a certain
cancer if a family member has that
type of cancer.
Heredity or Genetic Factors
Family History:
Women with a family history of
breast cancer have an increased risk
of developing breast cancer
themselves. In addition, some
families are at particularly high
risk of cancer due to hereditary
cancer syndromes. These families
often have multiple family members
with cancer, and are more likely to
develop cancer at a young age. In
the case of breast and ovarian
cancers, inherited mutations in two
genes - BRCA1 and BRCA2 - have been
found to greatly increase the
lifetime risk of developing breast
and ovarian cancer. Alterations in
these genes can be passed down
through either the mother's or the
father's side of the family.
BRCA1 and BRCA2 alterations are more
common in some ethnic groups. A
study of BRCA1 estimated that 12 out
of 1000 persons of Ashkenazi Jewish
descent have a BRCA1 alteration,
compared to 2.4 out of 1000 persons
in the non-Ashkenazi, non-Hispanic
white population. Approximately 2
percent of Ashkenazim (20 out of
1000) have one of three BRCA1 or
BRCA2 alterations specific to this
population. Less information is
available about the frequency of
BRCA1 or BRCA2 alterations in other
ethnic or racial groups, but a
recent study of 200 women with
breast cancer found that
African-American and white women had
a similar likelihood of having a
harmful BRCA1 or BRCA2 alteration.
Women with a BRCA1 or BRCA2
alteration are much more likely than
other women to develop breast or
ovarian cancer. Among women with a
BRCA1 or BRCA2 alteration, 36-85
percent will develop breast cancer
over the course of their lifetimes,
and 16-60 percent will develop
ovarian cancer; 2 the broad ranges
reflect differences in risk across
the different populations and
mutations that have been studied. By
comparison, among women in the
general U.S. population,
approximately 13 percent will
develop breast cancer and less than
2 percent will develop ovarian
cancer.
BRCA1 and BRCA2
alterations are not the only gene
alterations responsible for
hereditary breast cancer syndromes.
Other hereditary cancer syndromes
that increase breast cancer risk are
Li-Fraumeni syndrome, Cowden
syndrome, Peutz-Jeghers syndrome,
and Ataxia-Telangiectasia.Mutations
in the CHEK2 gene also appear to
contribute to some cases of familial
breast cancer.
Breast Density:
Breast density refers to the extent
of glandular and connective tissue
in the breast. Breasts with more
glandular and connective tissue-and
less fat-are denser. Women with
higher breast density are at
increased risk of developing breast
cancer. In addition, dense breasts
make it more difficult to detect
breast cancer by mammography..
History of Breast
Cancer: It is important to
realize the women who have been
cured of a primary breast cancer are
at increased risk for breast cancer
on the opposite side and that this
risk persists for 20 years or
more...
Environmental or Non-Genetic Factors
Reproductive
Factors: Several
reproductive factors have been
associated with an increased
incidence of breast cancer. These
include an early age at first
menstrual cycle, a late age at
menopause, and a late age at the
birth of the first child.
Postmenopausal Hormones:
Results from the Women's Health
Initiative suggest that
postmenopausal hormone therapy with
a combination of estrogen and
progestin increases the risk of
breast cancer. Furthermore, as use
of postmenopausal hormones has
declined, breast cancer incidence
has also declined; this provides
additional support for a link
between postmenopausal hormone use
and risk of breast cancer.
Alcohol: Moderate
alcohol consumption (often defined
as two or more drinks per day) has
consistently been linked with an
increased risk of breast cancer.
Obesity: In
premenopausal women, obesity has
been linked with a decreased risk of
breast cancer, possibly as a result
of disrupted menstrual cycles and
altered hormone levels. In
postmenopausal women, however,
obesity has consistently been linked
with an increased risk of breast
cancer. The link between obesity and
postmenopausal breast cancer appears
to be strongest among women who have
never used postmenopausal hormone
therapy, and may be explained by the
higher estrogen levels in obese
postmenopausal women. A recent study
has shown that weight gain in women
during adult life increases the risk
of postmenopausal breast cancer.
Radiation:
Women who have received radiation to
the chest for the treatment of
Hodgkin's lymphoma or other cancers
appear to have an increased risk of
breast cancer. A recent
international study has also shown
that women who have received low or
high dose radiation to the chest
have an increased risk of developing
breast cancer. Therapeutic doses of
radiation have long been known to
increase the risk of developing
breast cancer. However, this study
suggests that diagnostic procedures,
such as periodic chest X-rays, can
also increase the risk of developing
breast cancer.
DES:
Diethylstilbestrol (DES) is a
synthetic estrogen that was used
frequently in pregnant women between
the 1940s and 1960s. The drug was
used to reduce the risk of
miscarriages, though later studies
indicated that it most likely had no
effect on miscarriage risk. In 1971
a study reported that girls born to
women who had used DES (DES
daughters) had a greatly increased
risk of developing a certain type of
vaginal cancer. More recent research
suggests that DES daughters may also
have an increased risk of breast
cancer.
Exercise:
Many studies have shown
that women who exercise more have a
lower risk of developing breast
cancer than women with little
physical activity. One study
involving over 100,000 women
reported that long-term physical
activity lowers the risk of
developing breast cancer by one
third. A study from Europe found
that physical exercise reduced the
risk of postmenopausal breast cancer
by 20-80%.
Fresh
Fruits and Vegetables:
Researchers from France have
reported that an increased intake of
lignans, found primarily in fresh
fruits, vegetables and cereals,
decreases the risk of postmenopausal
breast cancer. However, not all
studies have shown a protective
effect of a high intake of fruits
and vegetables on reducing the
incidence of breast cancer.
Prevention
Cancer is
largely a preventable illness.
Two-thirds of cancer deaths in the
U.S. can be linked to tobacco use,
poor diet, obesity, and lack of
exercise. All of these factors can
be modified. Nevertheless, an
awareness of the opportunity to
prevent cancer through changes in
lifestyle is still
under-appreciated. However, the
situation with breast cancer is more
complex than with some other cancers
and the cause of most cases of
breast cancer remain unknown. The
risk factors, listed above, do not
account for the majority of cases of
breast cancer and we must continue
to seek these unknown causes.
Diet: Diet is a
fertile area for immediate
individual and societal intervention
to decrease the risk of developing
certain cancers. Numerous studies
have provided a wealth of
often-contradictory information
about the detrimental and protective
factors of different foods. There
is convincing evidence that excess
body fat substantially increases the
risk for many types of cancer. While
much of the cancer-related nutrition
information cautions against a
high-fat diet, the real culprit is
an excess of calories. Studies
indicate that there is little, if
any, relationship between body fat
and fat composition of the diet.
These studies show that excessive
caloric intake from both fats and
carbohydrates have the same result
of excess body fat. The ideal way to
avoid excess body fat is to limit
caloric intake and/or balance
caloric intake with ample exercise.
It is still important, however,
to limit fat intake, as evidence
still supports a relationship
between cancer and polyunsaturated,
saturated and animal fats.
Specifically, studies show that high
consumption of red meat and dairy
products can increase the risk of
certain cancers. One strategy for
positive dietary change is to
replace red meat with chicken, fish,
nuts and legumes.
High fruit
and vegetable consumption has been
associated with a reduced risk for
developing at least 10 different
cancers. This may be a result of
potentially protective factors such
as carotenoids, folic acid, vitamin
C, flavonoids, phytoestrogens and
isothiocyanates. These are often
referred to as antioxidants.
There is strong evidence that
moderate to high alcohol consumption
also increases the risk of certain
cancers. One reason for this
relationship may be that alcohol
interferes with the availability of
folic acid. Alcohol in combination
with tobacco creates an even greater
risk of certain types of cancer.
Exercise:
Life-long physical activity is an
important component of cancer
prevention and many studies have
shown that increased levels of
exercise decrease the risk of
developing breast cancer.
Breastfeeding:
Long-term breastfeeding may reduce a
woman's risk of developing breast
cancer by as much as 50%. In a study
conducted in China, researchers
found a significant association
between the duration of lactation
and a reduced breast cancer risk. In
this study, women who breastfed a
child for more than two years had a
54% reduced risk of developing
breast cancer, compared with women
who breastfed for 6 months or less.
In addition, the results indicated
that women who had a lifetime
duration of lactation anywhere from
73 to 108 months had a significantly
lower risk of developing breast
cancer. The risk was further
decreased for women who breastfed
for 109 or more months of their
lives. The researchers concluded
that prolonged lactation reduces the
risk of breast cancer and found that
both the duration of lactation per
child and the lifetime duration of
lactation were important factors.
Prevention for Women at High Risk
Women with a family
history of breast cancer and women
who carry the BRCA1 and BRCA2 genes
are at an increased risk of
developing breast cancer and may opt
to take more aggressive preventive
measures, such as the use of
anti-estrogen therapy, prophylactic
(preventive) bilateral mastectomy,
and/or prophylactic oophorectomy.
Chemoprevention:
Drugs that block the effects of
estrogen have been shown to reduce
the risk of breast cancer in women
at high risk of the disease. Two
drugs that have been approved for
breast cancer risk reduction in
certain groups of women are
tamoxifen and Evista (raloxifene).
Tamoxifen is approved for breast
cancer risk reduction in women who
are at high risk of the disease
(including high-risk premenopausal
women). Evista - originally approved
for the prevention and treatment of
osteoporosis - is approved for
breast cancer risk reduction in
postmenopausal women with
osteoporosis or postmenopausal women
at high risk of breast cancer.
To directly compare Evista to
tamoxifen in the prevention of
breast cancer in high-risk women,
researchers conducted a clinical
trial known to as the STAR trial
(The NSABP Study of Tamoxifen and
Raloxifene [STAR] P-2 Trial). The
study found that Evista is as
effective as tamoxifen in reducing
the risk of invasive breast cancer
in high-risk postmenopausal women,
but may be less effective in
reducing the risk of noninvasive
breast cancers such as ductal
carcinoma in situ (DCIS). Evista
carried a lower risk of blood clots
and cataracts than tamoxifen, but is
not without side effects. Evista has
been found to increase the risk of
blood clots and fatal strokes in
women with coronary heart disease or
at risk for coronary heart disease.
Bilateral Prophylactic
Mastectomy (Preventive removal of
both breasts): Women who
have a family history of breast
cancer and women who carry the BRCA1
and BRCA2 genes may reduce their
risk of developing breast cancer by
90% by undergoing bilateral
prophylactic mastectomy.
Prophylactic mastectomy is a drastic
measure that may decrease emotional
stress regarding the concern over
developing breast cancer; however,
it may also increase stress related
with self-esteem, sexuality and
femininity. Women considering this
procedure need to weigh the benefits
against the consequences, which
include the irreversibility of the
procedure, the psychological impact
and potential problems with implants
and reconstructive surgery. While
this procedure can greatly decrease
the risk of developing cancer, it is
not a guarantee that cancer will not
develop.
Prophylactic
Oophorectomy (Preventive removal of
the ovaries): The BRCA1 and
BRCA2 genes increase the risk of
both breast and ovarian cancer.
Since the ovaries produce estrogen,
which is linked to the development
of both cancers, some women who are
at a high risk for developing either
cancer will opt to have the ovaries
removed. This is an extreme measure
and the decision to undergo such a
procedure rests in the hands of the
patient. Women considering this
approach need to weigh the benefits
against the consequences, which
include sterility and the potential
that they could still develop
cancer. In addition, removal of both
ovaries prior to menopause can
introduce the issue of hormone
replacement therapy, which carries
its own risks.
Screening and Early Detection
For many types of cancer,
progress in the areas of cancer
screening and treatment has offered
promise for earlier detection and
higher cure rates. The term
screening refers to the regular use
of certain examinations or tests in
persons who do not have any symptoms
of a cancer but are at high risk for
that cancer. When individuals are at
high risk for a type of cancer, this
means that they have certain
characteristics or exposures, called
risk factors that make them more
likely to develop that type of
cancer than those who do not have
these risk factors. The risk factors
are different for different types of
cancer. An awareness of these risk
factors is important because 1) some
risk factors can be changed (such as
smoking or dietary intake), thus
decreasing the risk for developing
the associated cancer; and 2)
persons who are at high risk for
developing a cancer can often
undergo regular screening measures
that are recommended for that cancer
type. Researchers continue to study
which characteristics or exposures
are associated with an increased
risk for various cancers, allowing
for the use of more effective
prevention, early detection, and
treatment strategies. While all
women over the age of 40 should
undergo routine screening for breast
cancer, women who are at a high risk
for developing cancer may want to
begin this process at an earlier age
and with greater frequency.
Increasing surveillance can increase
the possibility that cancer could be
found at an early stage when
treatment is most likely to produce
a cure.
Annual
Clinical Breast Exam:
Regular physical examination plays a
vital role in the maintenance of
health. An annual gynecological
examination is an important
screening procedure for many types
of cancer and includes a physical
examination of the breasts. During
this procedure, a physician
physically examines the breasts to
feel for any lumps or
irregularities. The physician can
also use this procedure as an
opportunity to teach an individual
how to perform a breast self exam
(BSE). Women are encouraged to
perform a BSE every month, because
with regular examination they have a
greater chance of finding a lump
early in its development.
Mammography: It is recommended that
women over the age of 40 begin
having a yearly mammogram. A
mammogram is an x-ray image of the
breast that can reveal
irregularities and help to detect
cancer early when it is most
treatable. Mammography at 6-month
intervals is advised for younger
women at high risk of developing
breast cancer since they tend to
develop more rapidly growing
cancers.
Increasing
surveillance in women with a family
history of breast cancer might
increase the possibility that cancer
could be found at an early stage
when treatment is most likely to
produce a cure. In a multi-center
study, researchers compared
mammography performance among women
with a first-degree family history
of breast cancer with performance
among women of a similar age and no
family history. The results
indicated that the positive
predictive value of mammography
screening is higher among women with
a family history of breast cancer
than among those without a family
history. The number of cancer cases
per 1,000 mammography exams was 1.3
to 2 times higher among women with a
family history of breast cancer than
among those with no such history.
Furthermore, they found that the
rate of breast cancer detection
among women with a family history of
breast cancer was similar to the
rate found among women who were a
decade older and had no such
history.
Magnetic
Resonance Imaging (MRI):
MRI uses radio waves and a magnet to
create detailed images of the inside
of the body. The American Cancer
Society now recommends that women at
high risk of breast cancer undergo
yearly breast cancer screening with
breast MRI in addition to
mammography. These recommendations
were prompted by several studies of
MRI screening of women at high risk
of breast cancer. While these
studies found that the addition of
MRI to mammography increased the
frequency of false-positive test
results compared to mammography
alone, it also produced important
improvements in breast cancer
detection.
The following
groups were defined as candidates
for MRI and mammography based on
their elevated risk of breast
cancer:
- Women with a BRCA1
or BRCA2 mutation - Women who
have a first-degree relative
(parent, sibling, child) with a
BRCA1 or BRCA2 mutation, even if
they have yet to be tested
themselves - Women who have a
20-25% or greater risk of breast
cancer based on risk assessment
tools - Women who had radiation
to the chest between the ages of 10
and 30 years - Women who have
Li-Fraumeni syndrome, Cowden
syndrome, or
Bannayan-Riley-Ruvalcaba syndrome,
or may have one of these syndromes
based on a history in a first-degree
relative
The American Cancer
Society recommends against breast
MRI screening in women with a
lifetime risk of breast cancer of
less than 15 percent. The optimal
approach to the screening of women
with an intermediate risk of breast
cancer (lifetime risk between 15 and
20 percent) remains uncertain, and
these women are encouraged to
discuss their options with their
physician.
Predictive Genetic
Testing: The identification of the
breast cancer susceptibility genes,
BRCA1 and BRCA2, has led to
predictive genetic testing for these
genes. Since most breast cancers are
not the result of known inherited
mutations, not all women would
benefit from genetic testing.
However, women who appear to be at a
high risk may benefit from
undergoing a test to determine if
they do carry the BRCA1 or BRCA2
gene. An accurate genetic test can
reveal a genetic mutation, but
cannot guarantee that cancer will or
will not develop. At this point,
genetic tests are used to identify
individuals who are at an increased
risk of developing cancer, so that
these individuals may have the
option of taking preventive measures
Fiberoptic Ductoscopy:
Fiberoptic ductoscopy (FDS)
is a new technique that builds on
ductal lavage and allows physicians
to directly visualize the inside of
a milk duct. During this procedure,
a small, flexible tube containing a
video camera is inserted into the
milk duct, creating a live picture
of the inside lining of the duct.
This allows the physician to
visualize the lining of the milk
duct and identify any abnormalities.
As in ductal lavage, a salt-water
stream washes cells out of the duct
for examination under a microscope.
In clinical trials, fiberoptic
ductoscopy has proven effective in
identifying abnormal cellular
masses. This procedure is still
being evaluated in clinical trials,
but could potentially serve as an
additional screening procedure,
especially for women who are
experiencing nipple discharge.
New or Improved Imaging
Devices: Some new
developments in breast imaging are
aimed at decreasing the number of
false positive tests detected by
mammography which leads to a large
number of unnecessary breast
biopsies.
There are intense
research programs aimed at improving
sonography technology in order to
decrease the number of biopsies that
are performed for false positive
mammograms. One such technique is
called ultrasound elasticity imaging
which has showed high accuracy in
classifying cancerous and benign
breast changes. Another promising
approach is ultrasound tomography
which promises to be more accurate
than routine ultrasound.
Digital Mammography:
Current data suggests that
digital mammography is more accurate
than film mammography in certain
groups of women. Digital mammography
is primarily used to screen young
women with dense breasts but some
predict this will be a standard
technique.
Computer
Aided Detection (CAD): CAD
involves the use of a computer to
evaluate a digital mammographic
image. The technology marks areas of
the image that appear abnormal and
that should be reviewed further by
the radiologist. CAD doesn't replace
a radiologist's review of a
mammogram, but it can supplement it.
Some studies, however, have reported
that CAD doesn't increase breast
cancer detection and may increase
false-positive test results.
Digital Thermography:
Digital thermography is being used
to complement mammography and to
distinguish benign from malignant
lesions. The procedure uses changes
in temperature to identify cancerous
tissue, which will react differently
to thermal changes than normal
breast tissue. The procedure has
already proven effective in
identifying malignant lesions and
preventing unnecessary biopsies.
Tumor Biomarkers:
Researchers have begun to explore
the role of tumor biomarkers for the
early detection of breast cancer. In
one study, researchers analyzed
nipple aspirate fluids (NAFs) from
women with and without breast
cancer. The results of the study
indicated that the levels of
carcinoembryonic antigen (CEA) are
significantly higher in nipple fluid
from cancerous breasts than
tumor-free breasts. However, the
CEAs appear to be influenced by some
unknown systemic influence, which
might diminish the usefulness of the
biomarker for early breast cancer
detection. At this point, analysis
of nipple fluid CEA levels might be
used in combination with other
methods for the early detection of
cancer. Future research will help to
define the role of nipple fluid CEA
levels in the early detection of
breast cancer.
Improvements in Genetics:
Although the breast cancer
susceptibility genes, BRCA1 and
BRCA2, are similar, researchers have
found significant differences in the
genetic profiles of cancers that
result from mutations of these
genes. Usually BRCA2 mutations lead
to estrogen receptor-positive breast
cancer, whereas BRCA1 mutations lead
to estrogen receptor-negative breast
cancer. These differences indicate
inherent differences in the genes.
Researchers from the National
Institutes of Health evaluated and
compared the genetic profiles from
BRCA1 mutations, BRCA2 mutations and
sporadic breast cancers. They found
that the biological characteristics
of the tumors were significantly
different depending on which type of
genetic mutation caused the tumor.
The researchers concluded that an
inherited mutation influences the
gene-expression profile of the
cancer. The results of this study
have serious implications for the
future treatment of breast cancer
because the information could lead
to individualized treatment for
different types of breast cancer
that have historically been treated
as the same.
Again, the
above-mentioned techniques are new
areas of exploration in the
screening and early detection of
breast cancer. Clinical trials are
being utilized to determine the
effectiveness of these procedures.
While the results look promising and
the implications could be exciting,
these procedures are not yet the
standard. It is imperative that
women continue to utilize the
existing methods of screening for
breast cancer in order to ensure
early detection.
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