Causes Breast Cancer?
Although many risk factors may increase your
chance of developing breast cancer, it is not yet known
exactly how some of these risk factors cause cells to
become cancerous. A woman's hormones somehow stimulate
breast cancer growth. Just how this comes about has
not yet been figured out.
Researchers are beginning to understand how certain
changes in DNA can cause normal breast cells to become
cancerous. DNA is the chemical that carries the instructions
for nearly everything our cells do. We usually resemble
our parents because they are the source of our DNA.
However, DNA affects more than our outward appearance.
Some genes (parts of DNA) contain instructions for controlling
when our cells grow, divide, and die. Certain genes
that promote cell division are called oncogenes. Others
that slow down cell division, or cause cells to die
at the right time, are called tumor suppressor genes.
It is known that cancers can be caused by DNA mutations
(changes) that "turn on" oncogenes or "turn off" tumor
The BRCA genes (BRCA1 and BRCA2) are tumor suppressor
genes. When they are mutated, they no longer function
to suppress abnormal growth and cancer is more likely
to develop. Certain inherited DNA changes (you are born
with these) can cause an increased risk for developing
cancer in people who carry these changes and are responsible
for the cancers that run in some families.
Most DNA mutations related to breast cancer, however,
occur in single breast cells during a woman's life rather
than having been inherited. These acquired mutations
of oncogenes and/or tumor suppressor genes may result
from radiation or cancer-causing chemicals. So far,
studies have not been able to identify any chemical
in the environment or in our diets that is likely to
cause these mutations, or a subsequent breast cancer.
The cause of most acquired mutations remains unknown.
Women have already begun to benefit in several ways
from recent advances in understanding the genetic basis
of breast cancer. The section, "What Are the Risk Factors
for Breast Cancer?" explains how genetic testing can
identify some women who have inherited abnormal BRCA1,
BRCA2, CHEK-2, or p53 tumor suppressor genes. These
women can then take steps to reduce their risk of developing
breast cancers and to monitor changes in their breasts
carefully to find cancer at an earlier, more treatable
stage. (For more information see the American Cancer
Society documents, "Medicines to Reduce Breast Cancer
Risk" and "Breast Cancer Early Detection.")
Most breast cancers have several gene mutations that
are acquired. That means that these mutations are not
inherited. They develop as part of the cancer. Tests
to identify other acquired changes in oncogenes or tumor
suppressor genes (such as p53) may help doctors more
accurately predict the survival outcome of some women
with breast cancer. But with the exception of the HER2
oncogene, these tests have not yet been shown to be
useful in making decisions about treatment and are used
only for research purposes
Are the Risk Factors for Breast Cancer?
A risk factor is anything that increases your chance
of getting a disease, such as cancer. Different cancers
have different risk factors. For example, exposing skin
to strong sunlight is a risk factor for skin cancer.
Smoking is a risk factor for cancers of the lung, mouth,
larynx, bladder, kidney, and several other organs.
But having a risk factor, or even several, does not
mean that you will get the disease. Most women who have
one or more breast cancer risk factors never develop
the disease, while many women with breast cancer have
no apparent risk factors (other than being a woman and
growing older). Even when a woman with breast cancer
has a risk factor, there is no way to prove that it
actually caused her cancer.
There are different kinds of risk factors. Some factors,
like a person's age or race, can't be changed. Others
are linked to cancer-causing factors in the environment.
Still others are related to personal choices such as
smoking, drinking, and diet. Some factors influence
risk more than others, and your risk for breast cancer
can change over time, due to factors such as aging or
You Cannot Change
Simply being a woman is the main risk factor for developing
breast cancer. Although women have many more breast
cells than men, the main reason they develop more breast
cancer is because their breast cells are constantly
exposed to the growth-promoting effects of the female
hormones estrogen and progesterone, thus making breast
cancer much more common in women than men. Men can develop
breast cancer, but this disease is about 100 times more
common among women than men.
Your risk of developing breast cancer increases
as you get older. About 17% of invasive breast cancer
diagnoses are among women in their 40s, while about
78% of women with invasive breast cancer are age 50
or older when they are diagnosed.
risk factors: Recent studies have shown that
about 5% to 10% of breast cancer cases are hereditary
as a result of gene changes (called mutations). The
most common mutations are those of the BRCA1 and BRCA2
genes. Normally, these genes help to prevent cancer
by making proteins that keep cells from growing abnormally.
However, if you have inherited either mutated gene from
a parent, you are at increased risk for breast cancer.
Women with an inherited BRCA1 or BRCA2 mutation have
up to an 80% chance of developing breast cancer during
their lifetime and at a younger age than those women
who are not born with one of these gene mutations in
their cells. Women with these inherited mutations also
have an increased risk for developing ovarian cancer.
Although BRCA mutations are found most often in Jewish
women of Ashkenazi (Eastern Europe) origin, they are
also seen in African-American women and Hispanic women,
many of whom have the kind of mutation seen in Ashkenazi
Other genes have been discovered that might also lead
to inherited breast cancers. One of these is the ATM
gene. ATM stands for ataxia-telangiectasia mutation.
The gene is responsible for repairing damaged DNA. Certain
families with a high rate of breast cancer have been
found to have mutations of this gene. Another gene,
the CHEK-2 gene, also increases breast cancer risk about
twofold when it is mutated. Neither one of these genes,
however, is a frequent cause of familial breast cancer.
But in women who carry the CHEK-2 mutation and have
a strong family history of breast cancer, the risk is
Inherited mutations of the p53 tumor suppressor gene
can also increase your risk of developing breast cancer,
as well as leukemia, brain tumors, and/or sarcomas (cancer
of bones or connective tissue). The Li-Fraumeni syndrome,
named after the 2 researchers who described this inherited
cancer syndrome, is a rare cause of breast cancer.
If you are considering genetic testing, it is strongly
recommended that first you talk to a genetic counselor,
nurse, or doctor qualified to interpret and explain
these tests. It is very important to understand and
carefully weigh the benefits and risks of genetic testing
before these tests are done. Testing is expensive and
is not covered by some health insurance plans. There
is concern that people with abnormal genetic test results
will not be able to get life insurance or that coverage
may only be available at a much higher cost, but many
states have passed laws that prevent insurance companies
from denying insurance on the basis of genetic testing.
Family history of breast
cancer: Breast cancer risk is higher among
women whose close blood relatives have this disease.
Your risk of developing breast cancer is increased if:
You have 2 or more relatives with breast or ovarian
Breast cancer occurs before age 50 in a relative (mother,
sister, grandmother or aunt) on either side of the family.
The risk is higher if your mother or sister has a history
of breast cancer. You have relatives with both breast
and ovarian cancer.
You have 1 or more relatives with two cancers (breast
and ovarian, or 2 different breast cancers).You have
a male relative (or relatives) with breast cancer.
You have a family history of breast or ovarian cancer
and Ashkenazi Jewish heritage. Your family history includes
a history of diseases associated with hereditary breast
cancer such as Li-Fraumeni or Cowden Syndrome.
Having 1 first-degree relative (mother, sister, or daughter)
with breast cancer approximately doubles a woman's risk.
Having 2, first-degree relatives increases her risk
5-fold. Although the exact risk is not known, women
with a family history of breast cancer in a father or
brother also have an increased risk of breast cancer.
Altogether, about 20% to 30% of women with breast cancer
have a family member with this disease.
history of breast cancer: A woman with cancer
in one breast has a 3- to 4-fold increased risk of developing
a new cancer in the other breast or in another part
of the same breast. This is different from a recurrence
(return) of the first cancer.
White women are slightly more likely to develop breast
cancer than are African-American women. African-American
women are more likely to die of this cancer. Many experts
now feel that the main reason for this is because African-American
women have more aggressive tumors (see basal-like breast
cancer, below). The reasons for this are not known.
Asian, Hispanic, and Native-American women have a lower
risk of developing and dying from breast cancer.
Abnormal breast biopsy:
Some types of benign breast conditions are more closely
linked to breast cancer risk than others. Doctors often
divide benign breast conditions into 3 general groups,
depending on how they affect this risk: non-proliferative
lesions, proliferative lesions without atypia, and proliferative
lesions with atypia.
chest radiation: Women who as children or young
adults had radiation therapy to the chest area as treatment
for another cancer (such as Hodgkin disease or non-Hodgkin
lymphoma) are at significantly increased risk for breast
cancer. Some reports found the risk to be 12 times normal
risk. This varies with the age of the patient at the
time of radiation. Younger patients have a higher risk.
If chemotherapy was also given, the risk may be lowered
if the chemotherapy stopped ovarian hormone production.
The risk of developing breast cancer appears to be highest
if the breast was still in development (during adolescence)
when the radiation was given.
periods: Women who started menstruating at
an early age (before age 12) or who went through menopause
at a late age (after age 55) have a slightly higher
risk of breast cancer.
(DES): In the 1940s through the 1960s some
pregnant women were given diethylstilbestrol because
it was thought to lower their chances of losing the
baby (miscarriage). Recent studies have shown that these
women have a slightly increased risk of developing breast
cancer. Recent findings have also suggested that women
whose mothers took DES during pregnancy may have a higher
risk for breast cancer than women not exposed to the
drug in utero. For more information on DES see the American
Cancer Society document, "DES Exposure: Questions and
Factors and Breast Cancer Risk
Not having children: Women who have had no children
or who had their first child after age 30 have a slightly
higher breast cancer risk. Having multiple pregnancies
and becoming pregnant at an early age reduces breast
use: It is still not certain what part oral
contraceptives (birth control pills) might play in breast
cancer risk. Studies have suggested that women now using
oral contraceptives have a slightly greater risk of
breast cancer than women who have never used them. Women
who stopped using oral contraceptives more than 10 years
ago do not appear to have any increased breast cancer
risk. When considering using oral contraceptives, women
should discuss their other risk factors for breast cancer
with their health care team.
Postmenopausal hormone therapy (also known as hormone
replacement therapy, or HRT): It has become clear that
long-term use (several years or more) of postmenopausal
hormone therapy (PHT), particularly estrogen and progesterone
combined, increases your risk of breast cancer. Long-term
PHT use may also increase your chances of dying of breast
If you still have your uterus (womb), doctors generally
prescribe estrogen and progesterone (known as combined
PHT). Estrogen relieves menopausal symptoms and delays
osteoporosis (thinning of the bones that can lead to
fractures). But estrogen can increase the risk of developing
cancer of the uterus. Progesterone is added to help
If you no longer have your uterus, estrogen alone can
be prescribed. This is commonly known as estrogen replacement
therapy (ERT). This probably does not increase the risk
of breast cancer very much, if at all, especially if
used for a relatively short period of time.
Several large studies, including the Women's Health
Initiative (WHI), have found that there is an increased
risk of breast cancer related to the use of combined
PHT. The most recent results from the WHI found that
not only did combined PHT increase breast cancer risk,
but it also increased the likelihood that the cancer
would be found at a more advanced stage. This is because
it appeared to reduce the effectiveness of mammograms,
as more abnormal findings on mammograms were noted.
A large study from the United Kingdom has now found
that women who took the combined therapy were also more
likely to die of breast cancer than women who didn't.
The risk of PHT appears to apply only to current and
recent users, and a woman's breast cancer risk seems
to return to that of the general population within 5
years of stopping PHT.
Estrogen alone (ERT) does not appear to increase the
risk of developing breast cancer. But when used long
term (for more than 10 years), ERT has been found to
increase the risk of ovarian and breast cancer in some
At this time there appear to be few strong reasons to
use postmenopausal hormone therapy (combined PHT or
ERT), other than possibly for the temporary relief of
menopausal symptoms. In addition to the increased risk
of breast cancer, the WHI found that combined PHT also
increased the risk of heart disease, blood clots, and
strokes, and did not have a beneficial effect on mental
function or preventing Alzheimer's disease. It did lower
the risk of colorectal cancer and osteoporosis, but
this must be weighed against the possible harms, and
it should be considered that there are other effective
ways to prevent osteoporosis. And, as noted above, while
ERT did not seem to have much effect on the risk of
breast cancer, it did increase the risk of stroke.
The decision to use PHT should be made by the woman
and her doctor after weighing the possible risks (including
increased risk of heart disease, breast cancer, strokes,
and blood clots) and benefits (relief of menopausal
symptoms, reduced risk of osteoporosis), and considering
each woman's other risk factors for heart disease, breast
cancer, osteoporosis, and the severity of her menopausal
and pregnancy: Some studies suggest that breast-feeding
may slightly lower breast cancer risk, especially if
breast-feeding is continued for 1.5 to 2 years. Other
studies found no impact on breast cancer risk.
The explanation of this may be that both pregnancy and
breast-feeding reduce a woman's total number of lifetime
menstrual cycles. This may be similar to the reduction
of risk due to late menarche (start of menstrual periods)
or early menopause, which also decrease the total number
of menstrual cycles. One study concluded that having
more children and breast-feeding longer could reduce
the risk of breast cancer by half.
Use of alcohol is clearly linked to an increased risk
of developing breast cancer. The risk increases with
the amount of alcohol consumed. Compared with nondrinkers,
women who consume 1 alcoholic drink a day have a very
small increase in risk. Those who have 2 to 5 drinks
daily have about 1½ times the risk of women who drink
no alcohol. Alcohol is also known to increase the risk
of developing cancers of the mouth, throat, and esophagus.
The American Cancer Society recommends limiting your
consumption of alcohol.
and high-fat diets: Obesity (being overweight)
has been found to be a breast cancer risk in all studies,
especially for women after menopause. Although your
ovaries produce most of your estrogen, fat tissue produces
a small amount of estrogen. Having more fat tissue after
menopause can increase your estrogen levels and, thereby,
increase your likelihood of developing breast cancer.
The connection between weight and breast cancer risk
is complex, however. For example, risk appears to be
increased for women who gained weight as an adult but
is not increased among those who have been overweight
since childhood. Also, excess fat in the waist area
may affect risk more than the same amount of fat in
the hips and thighs. Researchers believe that fat cells
in various parts of the body have subtle differences
in their metabolism that may explain this observation.
Studies of fat in the diet have not clearly shown that
this is a breast cancer risk factor. Most studies found
that breast cancer is less common in countries where
the typical diet is low in total fat, low in polyunsaturated
fat, and low in saturated fat.
On the other hand, many studies of women in the United
States have not found breast cancer risk to be related
to dietary fat intake. Researchers are still not sure
how to explain this apparent disagreement. Many scientists
note that studies comparing diet and breast cancer risk
in different countries are complicated by other differences
(such as activity level, intake of other nutrients,
and genetic factors) that might also alter breast cancer
More research is needed to better understand the effect
of the types of fat eaten and body weight on breast
cancer risk. But it is clear that calories do count
and fat is a major source of these. A diet high in fat
has also been shown to influence the risk of developing
several other types of cancer, and intake of certain
types of fat is clearly related to heart disease risk.
The American Cancer Society recommends you maintain
a healthy weight throughout your life and limit your
intake of processed and red meats.
activity: Evidence is growing that physical
activity in the form of exercise reduces breast cancer
risk. The only question is how much exercise is needed.
In one study from the Women's Health Initiative (WHI)
as little as 1.25 to 2.5 hours per week of brisk walking
reduced a woman's risk by 18%. Walking 10 hours a week
reduced the risk a little more. The American Cancer
Society Guidelines on Nutrition and Physical Activity
for Cancer Prevention recommend that you engage in 45
to 60 minutes of intentional physical activity 5 or
more days a week.
with Uncertain, Controversial, or Unproven Effect on
Breast Cancer Risk
Antiperspirants: Internet e-mail rumors have suggested
that chemicals in underarm antiperspirants are absorbed
through the skin, interfere with lymph circulation,
cause toxins to build up in the breast, and eventually
lead to breast cancer. There is very little experimental
or epidemiological evidence to support this rumor. Chemicals
in products such as antiperspirants are tested thoroughly
to ensure their safety. One small study recently found
trace levels of parabens (used as preservatives in antiperspirants),
which have weak estrogen-like properties, in a small
sample of breast cancer tumors. However, the study did
not look at whether parabens caused the tumors. This
was a preliminary finding, and more research is needed
to determine what effect, if any, parabens may have
on breast cancer risk. On the other hand, a recent large
study of breast cancer causes found no increase in breast
cancer in women who used underarm antiperspirants or
shaved their underarms.
bras: Internet e-mail rumors and at least one
book have suggested that bras cause breast cancer by
obstructing lymph flow. There is no scientific or clinical
basis for this claim.
abortion: Several studies have provided very
strong data that induced abortions have no overall effect
on the risk of breast cancer. Also, there is no evidence
of a direct relationship between breast cancer and spontaneous
abortion (miscarriage) in most of the studies that have
been published. Scientists invited to participate in
a conference on abortion and breast cancer by the National
Cancer Institute (February 2003) concluded that there
was no relationship. A recent report of 83,000 women
with breast cancer found no link to a previous abortion,
either spontaneous (stillbirth) or induced.
Breast implants: Several
studies have found that breast implants do not increase
breast cancer risk although silicone breast implants
can cause scar tissue to form in the breast. Implants
make it harder to see breast tissue on standard mammograms,
but additional x-ray pictures called implant displacement
views can be used to more completely examine the breast
pollution: A great deal of research has been
reported and more is being done to understand environmental
influences on breast cancer risk. The goal is to determine
their possible relationships to breast cancer. Currently,
research does not show a clear link between breast cancer
risk and exposure to environmental pollutants, such
as the pesticide DDE (chemically related to DDT), and
PCBs (polychlorinated biphenyls).
smoke: Most studies have found no link between
active cigarette smoking and breast cancer. Though active
smoking has been suggested to increase the risk of breast
cancer in some studies, the issue remains controversial.
An issue that continues to be an active focus of scientific
research is whether secondhand smoke may increase the
risk of breast cancer. Both mainstream and secondhand
smoke contain about 20 chemicals that, in high concentrations,
cause breast cancer in rodents. Chemicals in tobacco
smoke reach breast tissue and are found in breast milk.
The evidence regarding secondhand smoke and breast cancer
risk in human studies is controversial, at least in
part because the risk has not been shown to be increased
in active smokers. One possible explanation for this
is that tobacco smoke may have different effects on
breast cancer risk in smokers and in those who are just
exposed to smoke.
A report from the California Environmental Protection
Agency in 2005 concluded that the evidence regarding
secondhand smoke and breast cancer is "consistent with
a causal association" in younger, mainly premenopausal
women. The 2006 US Surgeon General's report, The Health
Consequences of Involuntary Exposure to Tobacco Smoke,
concluded that there is "suggestive but not sufficient"
evidence of a link at this point. In any case, women
should be told that this possible link to breast cancer
is yet another reason to avoid contact with secondhand
Several studies have suggested that women who work at
night, for example, nurses on a night shift, may have
an increased risk of developing breast cancer. However,
this increased risk has not yet been proven and more
studies are in progress. According to some researchers,
the effect may be due to disruption in melatonin, a
hormone that is affected by light, but other hormones
are also being studied.
Breast Cancer Be Prevented?
A woman at average risk for breast cancer might reduce
her risk somewhat by changing those risk factors that
can be changed. If you give birth to several children
and breast-feed them for several months, avoid alcohol,
exercise regularly, and maintain a slim body, you are
decreasing your risk of getting breast cancer. Likewise,
avoiding PHT will avoid increasing your risk. (See the
section, "What Are the Risk Factors for Breast Cancer?".)
Other than these lifestyle changes, the most important
action a woman can take is to follow early detection
guidelines. Following the American Cancer Society's
guidelines for early detection (outlined in the section,
"Can Breast Cancer Be Found Early?") will not prevent
breast cancer but can help find cancers when the likelihood
of successful treatment is greatest.
If you are a woman with a strong family history of breast
cancer or with a known genetic mutation of a BRCA gene,
there are things you can do to reduce your chances of
developing breast cancer. We strongly recommend genetic
counseling before any of these steps. It is important
to know if your mutation is BRCA1 or BRCA2. BRCA1 cancers
may not be prevented by tamoxifen or raloxifene.
Also, if you have had DCIS, LCIS, or biopsies that have
shown premalignant or pre-cancerous changes, you might
also consider treatment to reduce your breast cancer
for BRCA gene: Recently the US Preventive Services
Task Force made recommendations for genetic testing.
They recommended that only people with a strong family
history should be evaluated. Women who are NOT of Ashkenazi
(Eastern European) Jewish heritage should be referred
for genetic evaluation if they have:
1. Two first-degree relatives with breast cancer, one
of whom was diagnosed when they were younger than 50,
2. Three or more first or second degree relatives diagnosed
with breast cancer at any age, or
3. A first degree relative diagnosed with cancer in
both breasts, or
4. Two or more first or second degree relatives diagnosed
at any age, or
5. A male relative with breast cancer
Women of Ashkenazi (Eastern European) Jewish heritage
should be referred for genetic evaluation if they have:
1. A first degree relative with breast or ovarian cancer
at any age or
2. Two second degree relatives on the same side of the
family with breast or ovarian cancer at any age.
Early Detection, Diagnosis
Based on scientific research and expert opinion, the
ACS has established recommendations to detect cancer
early in asymptomatic people (without symptoms of cancer).
The ACS believes that early detection examinations and
tests can help save lives and reduce suffering from
cancers of the breast, colon, rectum, cervix, prostate,
testis (testicles), oral cavity (mouth), and skin. Some
of these cancers can be found early by self examinations
(such as breast self-examination), physical examinations
by a health professional (such examinations of the breast,
thyroid gland, skin, colon and rectum, testicles, and
prostate), and by x-ray or laboratory tests (such as
mammography, the Pap test, and the prostate-specific
antigen or PSA blood test). In many cases, a combination
of two or more early detection approaches (such as mammography,
clinical breast examination by a health professional,
and breast self-examination) is the most effective strategy.
The 5-year relative survival rate for people with cancers
for which the ACS has specific early detection recommendations
(breast, colon, rectum, cervix, prostate, testis, oral
cavity, and skin) is about 82%. The 5-year survival
rate is defined as the percentage of people alive at
least five years after diagnosis of cancer. The 5-year
relative survival rate calculation excludes people who
die of other causes. Both rates include people regardless
of the type of treatment, if any, they receive. The
outlook for survival for people with these cancers is
greatly improved by early detection.
Is Breast Cancer Diagnosed?
If screening tests or your signs and symptoms suggest
breast cancer, your doctor will use one or more methods
to determine if the disease is present and to evaluate
the stage of the cancer.
Although widespread use of screening mammograms has
increased the number of breast cancers found before
they cause any symptoms, some breast cancers are not
found by mammogram, either because the test was not
done or because, even under ideal conditions, mammograms
cannot find every breast cancer.
The most common sign of breast cancer is a new lump
or mass. A painless, hard mass that has irregular edges
is more likely to be cancerous, but some cancers are
tender, soft, and rounded. For this reason, it is important
that a health care professional experienced in diagnosing
breast diseases check any new breast mass or lump.
Other signs of breast cancer include a generalized swelling
of part of a breast (even if no distinct lump is felt),
skin irritation or dimpling, nipple pain or retraction
(turning inward), redness or scaliness of the nipple
or breast skin, or a discharge other than breast milk.
Sometimes a breast cancer can spread to underarm lymph
nodes and cause swelling there even before the original
tumor in the breast tissue is large enough to be felt.
Medical History and Physical
The first step in evaluation of a woman with suspected
breast cancer is a complete medical history and physical
exam. Your doctor will ask questions about your symptoms,
any other health problems, and risk factors for benign
breast conditions and breast cancer (such as whether
any of your relatives had benign breast conditions,
breast cancer, ovarian cancer, or other cancers).
Your breast will be thoroughly examined to locate any
lump or suspicious area and to feel its texture, size,
and relationship to the skin and chest muscles. Any
changes in the nipples or the skin of your breast will
be noted. The lymph nodes under the armpit and above
the collarbones may be palpated (felt), because enlargement
or firmness of these lymph nodes might indicate spread
of breast cancer. Your doctor will also perform a complete
physical exam to judge your general health and whether
there is any evidence the cancer has spread.
In addition to the medical history and physical exam,
imaging tests and biopsies may be done.
Tests to Diagnose Breast Disease
Although mammograms are mostly used for screening, they
can also be used to examine the breast of a woman who
has a breast problem. This can be a breast mass, nipple
discharge, or an abnormality that was found on a screening
mammogram. In some cases, special images known as cone
views with magnification are used to make a small area
of altered breast tissue easier to evaluate.
A diagnostic mammogram may show that a lesion (area
of abnormal tissue) has a high likelihood of being benign
(not cancer). In these cases, it is common to ask the
woman to come back sooner than usual for a recheck,
usually in 4 to 6 months. On the other hand, a diagnostic
mammogram may show that the abnormality is not worrisome
at all, and the woman can then return to having routine
yearly mammograms. Finally, the diagnostic work-up may
suggest that a biopsy is needed to tell if the lesion
is cancer. Even if the mammograms show no tumor, if
you or your doctor can feel a lump, then usually a biopsy
will be needed to make sure it isn't cancer. One exception
would be if an ultrasound exam finds that the lump is
The American Cancer Society believes the use of mammograms,
clinical breast exam, and breast self exam, according
to the recommendations previously outlined, offers women
the best opportunity for reducing the breast cancer
death rate through early detection. This combined approach
is clearly better than any one exam. Without question,
a breast physical exam without a mammogram would miss
the opportunity to detect many breast cancers that are
too small for a woman or her doctor to feel but can
be seen on mammograms. Although a mammogram is the most
sensitive screening method, a small percentage of breast
cancers do not show up on mammograms but can be felt
by a woman or her doctors.
Breast ultrasound: Ultrasound has become a
valuable tool to use with mammography because it is
widely available and less expensive than other options,
such as MRI. Usually, breast ultrasound is used to target
a specific area of concern found on the mammogram. Ultrasound
also helps distinguish between cysts and solid masses
and between benign and cancerous tumors. Ultrasound
may be most helpful in women with high breast density
(thickness). The National Cancer Institute (NCI) is
sponsoring a clinical trial to evaluate the benefits
and risks of adding screening breast ultrasound to screening
mammograms in women with dense breasts and a higher
risk of breast cancer.
Ultrasound, also known as sonography, uses high-frequency
sound waves to outline a part of the body. High-frequency
sound waves are transmitted into the area of the body
being studied and echoed back. These echoes are picked
up by the ultrasound probe. A computer changes the sound
waves into an image that is displayed on a screen. You
are not exposed to radiation during this test.
Ductogram: This test,
also called a galactogram, is sometimes helpful in determining
the cause of bloody nipple discharge. In this test a
fine plastic tube is placed into the opening of the
duct at the nipple. A small amount of contrast medium
is injected, which outlines the shape of the duct on
an x-ray image, which will show if there is a mass inside
mammogram (FFDM): A full-field digital mammogram
is similar to a standard mammogram in that x-rays are
used to produce an image of your breast. The differences
are in the way the image is recorded, viewed by the
doctor, and stored. Standard mammograms are recorded
on large sheets of photographic film. Digital mammograms
are recorded and stored on a computer. After the exam,
the doctor can view them on a computer screen and adjust
the image size, brightness, or contrast to see certain
areas more clearly. Digital images can also be sent
electronically to another site for a remote consult
with breast specialists. While many centers do not offer
the digital option at this time, it is expected to become
more widely available in the future.
Because digital mammograms cost more than standard mammograms,
studies are now under way to determine which form of
mammogram will benefit more women in the long run. Some
studies have found that women who have a FFDM have to
return less often for additional imaging tests because
of inconclusive areas on the original mammogram. A recent
large study from the National Cancer Institute found
that a FFDM was more accurate in finding cancers in
women younger than 50 and in women with dense breast
tissue, although the rates of inconclusive results were
similar between a FFDM and a film mammogram. It is important
to remember that a standard film mammogram also is effective
for these groups of women, and that they should not
miss their regular mammogram if a digital mammogram
is not available.
Computer-aided detection and diagnosis (CAD): Over the
past 2 decades, computer-aided detection and diagnosis
(CAD) has been developed to help radiologists detect
suspicious changes on mammograms. This is done most
commonly with screen-film mammograms and less often
with digital mammograms. Generally, the computer device
will scan the mammogram first. It can find tumors that
the radiologist can't spot. The radiologist, knowing
the results of the CAD, will then review the films to
look for lesions the CAD missed. The radiologist will
then decide the seriousness of the lesions the CAD found.
Early research results suggest that CAD systems help
radiologists diagnose more early stage cancers than
In scintimammography, a radioactive tracer is injected
into a vein to detect breast cancer cells. The tracer
attaches to breast cancers and is detected by a special
camera. This is a very new technique and is still considered
experimental. It may or may not be helpful in evaluating
This technology is an extension of a digital mammogram.
Tomosynthesis allows the breast to be viewed as many
thin slices and has the possibility of providing a more
accurate and earlier diagnosis of breast cancer. This
technology is still considered experimental and is not
yet commercially available.
resonance imaging (MRI): MRI scans use radio
waves and strong magnets instead of x-rays. The energy
from the radio waves is absorbed and then released in
a pattern formed by the type of tissue and by certain
diseases. A computer translates the pattern of radio
waves given off by the tissues into a very detailed
image of parts of the body. A contrast material called
gadolinium is often injected to better see details.
Patients have to lie inside a tube, which is confining
and can upset people with claustrophobia (a fear of
enclosed spaces). The machine also makes a thumping
noise that you may find disturbing. Some places provide
headphones with music to block this out. MRIs are very
expensive, although insurance plans generally pay for
them once cancer is diagnosed.
Although MRI machines are quite common, they need to
be specially adapted to look at the breast. They can
be used to better examine cancers found by mammogram
or for screening women who have a high risk of developing
breast cancer. A few recent studies have shown that
MRI screening for women at increased risk finds more
cancers than a standard mammogram. However, it is not
yet known if the difference between MRI and mammograms
in finding small cancers is great enough to save additional
lives. And the MRI studies found many more abnormalities
that were not cancers, which led to an increased number
of biopsy procedures.
MRI is also used for women who have been diagnosed with
breast cancer. It is used to better determine the actual
size of the cancer and to look for any other cancers
in the breast.
Nipple discharge exam: If you have spontaneous nipple
discharge, some of the fluid may be collected and looked
at under a microscope to see if any cancer cells are
in it. Most nipple discharges or secretions are not
cancer. In general, if the secretion appears clear green
in color, or milky, cancer is very unlikely. If the
discharge is red or red-brown, suggesting that it contains
blood, it might possibly be caused by cancer, although
an injury, infection, or benign tumor are more likely
Even when no cancer cells are found in a nipple discharge,
it is not possible to say for certain that a breast
cancer is not present. If a patient has a suspicious
mass, a biopsy is necessary, even if the nipple discharge
does not contain cancer cells.
Ductal lavage and nipple aspiration: Ductal lavage is
an experimental test developed for women who have no
symptoms of breast cancer but are at very high risk
for the disease. It is not a test to screen for or diagnose
breast cancer, but it may help give a more accurate
picture of a woman's risk of developing it.
Ductal lavage can be done in a doctor's office or an
outpatient facility. An anesthetic cream is applied
to numb the nipple area. Gentle suction is then used
to help draw tiny amounts of fluid from the milk ducts
up to the nipple surface. The fluid droplets that appear
help locate the milk ducts' natural openings on the
surface of the nipple. A tiny tube (called a catheter)
is then inserted into a milk duct opening on the nipple.
A small amount of anesthetic is infused into the duct
to numb the inside. Saline (salt water) is slowly delivered
through the catheter to gently "rinse" the duct and
collect cells. The ductal fluid is withdrawn through
the catheter and placed into a collection vial. The
vial is then sent to a lab, where the cells are viewed
under a microscope.
Ductal lavage is not considered appropriate for women
who aren't at high risk for breast cancer. It is not
clear whether it will ever be a useful tool. The test
has not been shown to detect cancer early. It is much
more useful as a test of cancer risk rather than as
a screening test for cancer. More studies are needed
to better define the usefulness of this test.
Nipple aspiration also looks for abnormal cells arising
in the ducts, but is much simpler, in that nothing is
inserted into the breast. The device for nipple aspiration
uses small cups that are placed on the woman's breasts.
The device warms the breasts, gently compresses them,
and applies light suction to bring nipple fluid to the
surface of the breast. The nipple fluid is then collected
and sent to a lab for analysis. As with ductal lavage,
the procedure may be useful as a test of cancer risk
but is not appropriate as a screening test for cancer.
The test has not been shown to detect cancer early.
A biopsy is done when mammograms, ultrasound, or the
physical exam finds a breast change (or abnormality)
that is possibly cancer. A biopsy is the only way to
tell if cancer is really present. All biopsy procedures
remove a tissue sample for examination under a microscope.
There are several types of biopsies, such as fine needle
aspiration biopsy, core (large needle) biopsy, and surgical
biopsy. Each type of biopsy has its own advantages and
The choice of which to use depends on your specific
situation. Some of the factors your doctor will consider
include how suspicious the lesion appears, how large
it is, where in the breast it is located, how many lesions
are present, other medical problems you may have, and
your personal preferences. You might want to discuss
the advantages and disadvantages of different biopsy
types with your doctor.
needle aspiration biopsy (FNAB): A
thinner needle is used for FNAB than the ones used for
blood tests. The needle can be guided into the area
of the breast change while the doctor is feeling (palpating)
the lump. The doctor can be a pathologist, radiologist,
or surgeon. If the lump can't be felt easily, the doctor
might use ultrasound or a method called stereotactic
needle biopsy to guide the needle, although most of
the time if a stereotactic device is used, a large needle
(core) biopsy is done.
Ultrasound lets the doctor watch the needle on a screen
as it moves toward and into the mass. For stereotactic
needle biopsy, computers map the exact location of the
mass using mammograms taken from 2 angles. Then a computer
guides the needle to the right spot.
A local anesthetic (numbing medicine) may or may not
be used. Because such a thin needle is used for the
biopsy, the process of getting the anesthetic may actually
be more uncomfortable than the biopsy itself.
Once the needle is in place, fluid is drawn out. If
the fluid is clear, the lump is probably a benign cyst.
Bloody or cloudy fluid can mean either a benign cyst
or, very rarely, a cancer. If the lump is solid, small
tissue fragments are drawn out. A pathologist (a doctor
specializing in diagnosing disease from tissue samples)
will examine the biopsy tissue or fluid to determine
if it is cancerous.
Fine needle aspiration biopsies can sometimes miss a
cancer and take benign cells from nearby the cancer.
If it does not provide a clear diagnosis, or your doctor
is still suspicious, a second biopsy or a different
type of biopsy should be performed. Stereotactic core
needle biopsy: A core biopsy can sample breast changes
felt by the doctor, as well as smaller ones pinpointed
by ultrasound or mammogram. Depending on whether the
abnormal area can be felt, about 3 to 5 cores are usually
The needle used in core biopsies is larger than that
used in FNAB. It removes a small cylinder of tissue
(about 1/16- to 1/8-inch in diameter and ½-inch long)
from a breast abnormality. The biopsy is done with local
anesthesia in an outpatient setting.
Two new stereotactic biopsy methods can remove more
tissue than a core biopsy. The Mammotome® is also known
as vacuum-assisted biopsy. For this procedure the skin
is numbed and a small incision (about ¼ inch) is made.
A probe is inserted through the incision into the abnormal
area of breast tissue. A cylinder of tissue is suctioned
into the probe then a rotating knife within the probe
cuts the tissue sample from the rest of the breast.
The Mammotome procedure is done as an outpatient. No
stitches are needed and there is minimal scarring. This
method usually removes about twice as much tissue as
core biopsies. The ABBI method (short for Advanced Breast
Biopsy Instrument) uses a probe with a rotating circular
knife and thin heated electrical wire to remove a large
cylinder of abnormal tissue.
In some centers, the biopsy is guided by an MRI, which
locates the tumors, plots its coordinates, and aims
the stereotactic biopsy device into the tumor.
Sometimes, a surgeon is needed to remove all or part
of the lump for microscopic examination. An excisional
biopsy removes an entire lesion (breast abnormality
such as a mass or area containing calcifications), as
well as a surrounding margin of normal-appearing breast
tissue. In rare circumstances, this type of biopsy can
be done in the doctor's office, but it is more commonly
done in the hospital's outpatient department under a
local anesthesia (you are awake during the procedure,
but your breast is numb). Intravenous sedation is often
given to make you less aware of the procedure.
During an excisional breast biopsy the surgeon may use
a procedure called wire localization if there is a small
lump that is hard to locate by touch or if an area looks
suspicious on the x-ray but cannot be felt. After the
area is numbed with local anesthetic, a thin hollow
needle is placed into the breast and x-ray views are
used to guide the needle to the suspicious area. A thin
wire is inserted through the center of the needle. A
small hook at the end of the wire keeps it in place.
The hollow needle is then removed, and the surgeon uses
the wire to guide him to the abnormal area to be removed.
If a benign condition is diagnosed, no further treatment
is needed. If the diagnosis is cancer, there is time
for you to learn about the disease and to discuss all
treatment options with your cancer care team, friends,
and family. There is no need to rush into treatment.
You may wish to obtain a second opinion before deciding
on what treatment is best for you.
Tests to Detect Breast Cancer Spread
x-ray: This test may be done to see whether
the breast cancer has spread to your lungs.
Bone scan: This procedure
helps show if a cancer has metastasized (spread) to
your bones. The patient receives an injection of radioactive
material called technetium diphosphonate. The amount
of radioactivity used is very low and causes no long-term
effects. The radioactive substance is attracted to diseased
bone cells throughout the entire skeleton. Areas of
diseased bone will be seen on the bone scan image as
dense, gray to black areas, called "hot spots."
These areas may suggest metastatic cancer is present,
but arthritis, infection, or other bone diseases can
also cause a similar pattern. To distinguish among these
conditions, the cancer care team may use other imaging
tests or take bone biopsies. Bone scans can find metastases
earlier than regular x-rays but sometimes, even when
the cancer has spread to the bones, the bone scan won't
show it. Other imaging studies such as CT or MRI will
(CT): The CT scan is an x-ray procedure that
produces detailed cross-sectional images of your body.
Instead of taking one picture, like a regular x-ray,
a CT scanner takes many pictures as it rotates around
you. A computer then combines these pictures into an
image of a slice of your body. The machine creates several
pictures of the part of your body that is being studied.
This test can help tell if your cancer has spread into
your liver or other organs. Often after the first set
of pictures is taken you will receive an intravenous
injection of a contrast agent, or "dye," that helps
better outline structures in your body. A second set
of pictures is then taken.
CT scans can also be used to precisely guide a biopsy
needle into a suspected metastasis. For this procedure,
called a CT-guided needle biopsy, you remain on the
CT scanning table while a radiologist advances a biopsy
needle toward the location of the mass. CT scans are
repeated until the doctors are sure that the needle
is within the mass. A fine needle biopsy sample (tiny
fragment of tissue) or a core needle biopsy sample (a
thin cylinder of tissue about ½-inch long and less than
1/8-inch in diameter) is removed and sent to be examined
under a microscope.
CT scans take longer than regular x-rays. You need to
lie still on a table, and the part of your body being
examined is placed within the scanner, a doughnut-shaped
machine that completely surrounds the table. The test
is painless, but you may find it uncomfortable to hold
still in certain positions for minutes at a time.
You will need an IV (intravenous) line through which
the contrast dye is injected. The injection can also
cause some flushing (redness and warm feeling). Some
people are allergic and get hives or, rarely, more serious
reactions like trouble breathing and low blood pressure
can occur. Be sure to tell the doctor if you have ever
had a reaction to any contrast material used for x-rays.
You may be asked to drink 1 to 2 pints of a solution
of contrast material. This helps outline the intestine
so that it is not mistaken for tumors.
resonance imaging (MRI): This is described
above as a way of looking for breast cancer as a supplement
to mammograms. Traditionally, MRI scans have been used
to look for cancer spread, just like CT scans. MRI scans
are particularly helpful in examining the brain and
spinal cord. MRI scans are a little more uncomfortable
than CT scans. First, they take longer -- often up to
an hour. Second, you have to lie inside a narrow tube,
which is confining and can upset people with claustrophobia
(a fear of enclosed spaces). The machine also makes
a thumping noise that you may find disturbing. Some
centers provide headphones with music to block this
tomography (PET): PET uses glucose (a form
of sugar) that contains a radioactive atom, which is
injected into a vein and travels throughout the body.
A special camera can detect the radioactivity. Cancer
cells of the body absorb large amounts of the radioactive
sugar, because of the high amount of energy that they
use. PET is useful when your doctor thinks the cancer
has spread but doesn't know where. A PET scan can be
used instead of several different x-rays because it
scans your whole body. Some of the newer machines are
able to perform both a PET and CT scan at the same time
(PET/CT scan). This allows the radiologist to compare
areas of higher radioactivity on the PET with the appearance
of that area on the CT.
It is important to follow the eating, drinking, and
activity directions you are given before the PET scan.
This test can be used as a diagnostic aid to a mammogram,
especially in looking for cancer in axillary lymph nodes.
So far, most studies show it isn't very sensitive in
finding small deposits of cancer in lymph nodes, although
it can find big ones.
Examination of Breast Cancer Tissue
of breast cancer: The tissue removed during
the biopsy is examined in the lab to see whether the
cancer is in situ (not invasive) or invasive. The biopsy
is also used to determine the cancer's type. The different
types of breast cancer are defined in the section, ""What
Is Breast Cancer?".
The most common types, invasive ductal and invasive
lobular cancer, are treated in the same way. In some
cases, breast cancer types that tend to have a more
favorable prognosis (medullary, tubular, and mucinous
cancers) are treated differently. For example, hormone
therapy or chemotherapy may be recommended for small
stage I cancers with unfavorable microscopic features,
but not for small cancers of the types associated with
a more favorable prognosis.
of breast cancer: A pathologist looks at the
tissue sample under a microscope and then assigns a
grade to it. The grade helps predict the patient's prognosis
because cancers that closely resemble normal breast
tissue tend to grow and spread more slowly. In general,
a lower grade number indicates a slower-growing cancer
that is less likely to spread, while a higher number
indicates a faster-growing cancer that is more likely
Histologic tumor grade (sometimes called its Bloom-Richardson
grade, Scarff- Bloom-Richardson grade, or Elston-Ellis
grade) is based on the arrangement of the cells in relation
to each other: whether they form tubules; how closely
they resemble normal breast cells (nuclear grade); and
how many of the cancer cells are in the process of dividing
(mitotic count). This system of grading is used for
invasive cancers but not for in situ cancers.
Grade 1 (well-differentiated)
cancers have relatively normal-looking cells that do
not appear to be growing rapidly and are arranged in
2 (moderately differentiated) cancers have
features between grades 1 and 3.
3 (poorly differentiated) cancers, the highest
grade, lack normal features and tend to grow and spread
The tumor grade is most important in patients with small
tumors without lymph node involvement. Patients with
small, well-differentiated tumors may require no further
treatment after the tumor is removed, while patients
with moderately or poorly differentiated tumors usually
receive additional hormonal or chemotherapy.
What's New in Breast Cancer Research
Studies continue to uncover lifestyle factors and habits
that alter breast cancer risk. Ongoing studies are looking
at the effect of exercise, weight gain or loss, and
diet on breast cancer risk. Studies on the best use
of genetic testing for BRCA1 and BRCA2 mutations continue
at a rapid pace. Other genes are being identified. This
will occur more rapidly now that the human genome has
Perhaps the most important finding, though, has been
that combined estrogen and progestin (not estrogen alone)
when used as postmenopausal hormone therapy increases
a woman's risk of developing breast cancer.
A large, long-term study funded by the National Institute
of Environmental Health Sciences (NIEHS) is now underway
to help find the causes of breast cancer.
Recent results of studies that are still in progress
suggest that selective estrogen-receptor modulators
(SERMs) lower breast cancer risk in women with certain
breast cancer risk factors. Further research with SERMs,
such as tamoxifen (also used in breast cancer treatment)
and raloxifene and drugs such as aromatase inhibitors,
is expected to lead to ways to prevent many breast cancers.
So far, most women are reluctant to take these medications
because of concern about side effects.
A new biopsy technique now makes it possible to obtain
tissue samples during a vacuum-assisted breast biopsy
procedure with magnetic resonance imaging (MRI)-assisted
guidance. This method allows many samples to be taken
through a single small incision in the skin, using only
local anesthesia (numbing of the area). This biopsy
technique is being studied in women with a personal
or family history of breast cancer, those who have undergone
previous breast surgery, and women with dense breast
tissue who cannot get accurate screenings with tests
such as ultrasound or mammograms.
Although the number of women with breast cancer choosing
breast conservation therapy has been steadily increasing,
there are some women who, for medical or personal reasons,
choose mastectomy. Some of them also choose to have
reconstructive surgery to restore the breast's appearance.
Technical advances in microvascular surgery (reattaching
blood vessels) have made free flap procedures an option
for breast reconstruction. Recent studies suggest that
a new procedure known as skin-sparing mastectomy is
as effective as the usual type of modified radical mastectomy
for many women. This new procedure offers the advantage
of less scar tissue and a reconstructed breast that
seems more natural.
For several years, concern over a possible link between
breast implants and immune system diseases has discouraged
some women from choosing implants as a method of breast
reconstruction. Recent studies have thoroughly reviewed
this complex issue. Although women should be aware that
implants can cause some side effects (such as firm or
hard scar tissue formation), they can be assured that
women with implants do not have any greater risk for
immune system diseases than women who have not had this
Similarly, the concern that breast implants increase
the risk of breast cancer recurrence or formation of
new cancers is not supported by current evidence.
Dose Dense Chemotherapy
Recent research has suggested that giving chemotherapy
more often (every 2 weeks) at the usual doses may work
better in preventing recurrence than the usual schedule
(every 3 weeks). Clinical trials are in progress to
define the role of dose density in adjuvant therapy.
Because of this aggressive schedule, growth factors
must be given to prevent low blood counts, a common
and serious side effect of chemotherapy.
Antibodies are proteins produced by immune system cells
that attach to certain chemicals that the body recognizes
as not being part of its own normal tissues. Antibodies
help your body resist infections, and even cancer.
Monoclonal antibodies are a special type of antibody
that can be mass-produced in laboratories. Trastuzumab
is the first monoclonal antibody drug used to treat
women with breast cancer. It works by preventing the
HER2/neu protein from promoting excessive growth of
breast cancer cells and may also help the immune system
fight the cancer.
Other monoclonal antibodies that recognize the HER2/neu
protein are being tested in clinical trials, as are
monoclonal antibodies that block other growth-promoting
molecules of breast cancer cells. Monoclonal antibodies
that have been designed to guide immune system cells,
chemotherapy drugs, or radiation therapy directly to
the tumor are also being tested.
In order for cancers to grow, blood vessels must develop
to nourish the cancer cells. This process is called
angiogenesis. Looking at angiogenesis in breast cancer
specimens can help predict prognosis. Some studies have
found that breast cancers surrounded by many new, small
blood vessels are likely to be more aggressive. Bevacizumab
is an anti-angiogenesis drug that doctors have recently
begun using in combination with the chemotherapy drug
paclitaxel in patients with metastatic breast cancer.
New drugs are being developed that may be useful in
stopping breast cancer growth by preventing new blood
vessels from forming. Several of these drugs are being
tested in clinical trials, and studies of new, more
potent anti-angiogenesis drugs are expected to begin
Studies and New Breast Cancer Classifications
One of the mysteries of breast cancer is that doctors
cannot always accurately predict which women have a
higher risk that their cancer will come back. That is
why almost every woman, except for those with small
tumors, receives some sort of treatment after surgery.
To better pick out who will need adjuvant therapy, researchers
have looked at many aspects of breast cancers. The best
test seems to be one that looks at the genes in breast
cancer cells. Scientists have been able to link certain
patterns of genes with more aggressive cancers -- those
that tend to come back and spread to distant sites.
Preliminary studies suggest that some women with favorable
patterns might be able to avoid adjuvant therapy after
surgery, but most experts feel that more research is
needed before this new technology should be used routinely.
Research using sophisticated technology for detecting
patterns of gene expression has suggested some new ways
of classifying breast cancers. The current types of
breast cancer are based on appearance of tumors under
a microscope. It appears that a new classification,
based on molecular features, may be better able than
the current classification to predict prognosis and
response to several types of breast cancer treatment.
The new research suggests four types of breast cancers:
Luminal A and Luminal B types: The luminal types are
estrogen receptor positive, usually low grade, and tend
to grow slowly. The gene expression patterns of these
cancers are similar to normal cells that line the breast
ducts and glands (the lining of a duct or glad is called
its lumen). Luminal A cancers have the best prognosis.
Luminal B cancers generally grow somewhat faster than
the luminal A cancers and their prognosis is not quite
These cancers have extra amounts of HER2 DNA, RNA, and
protein. They usually have a high grade appearance under
the microscope. These cancers tend to grow rapidly and
have a poor prognosis, although they often can be treated
successfully with trastuzumab.
type: These cancers lack estrogen receptors
and have normal amounts of HER2. These are high-grade
cancers that grow rapidly and have a poor prognosis.
This type is common among women with BRCA gene mutations.
For reasons that are not well understood, this cancer
is particularly common among young African-American
Research continues in this area as scientists look for
ways to apply new technology to better understand and
improve the treatment of breast cancer.
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