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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.
Signs and Symptoms
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 do not
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 any new breast mass or lump be checked by
a health care professional experienced in diagnosing breast diseases.
Other possible signs of breast cancer include:
- swelling of all or part of a breast (even if no distinct
lump is felt)
- skin irritation or dimpling
- breast or nipple pain
- nipple retraction (turning inward)
- redness, scaliness, or thickening of the nipple or breast
skin
- a discharge other than breast milk
Sometimes a breast cancer can spread to underarm lymph nodes and cause
a lump or swelling there, even before the original tumor in the breast
tissue is large enough to be felt.
Medical History and Physical Exam
If you have any signs or symptoms that might be due to breast
cancer, be sure see your doctor as soon as possible. Your doctor will
want to ask questions about your symptoms, any other health problems,
and possible risk factors for benign breast conditions or breast
cancer.
Your breasts will be thoroughly examined for any lumps or
suspicious areas and to feel their texture, size, and relationship to
the skin and chest muscles. Any changes in the nipples or the skin of
your breasts 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 probably do a complete physical exam to judge your
general health and whether there is any evidence of cancer that may
have spread.
If breast symptoms and/or the results of the physical exam
suggest breast cancer might be present, more involved tests will likely
be done. These might include imaging tests, looking at samples of
nipple discharge, or doing biopsies of suspected areas.
Imaging Tests Used to Evaluate
Breast Disease
Diagnostic Mammograms
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 abnormal 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 her next mammogram, usually in 4 to 6 months. 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 mammogram 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 a simple cyst (a fluid-filled sac), which is very unlikely
to be cancerous.
Full-field
digital mammogram (FFDM): A full-field digital mammogram
(or just "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 look at 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 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.
Computers can help doctors identify abnormal areas on a
mammogram by acting as a second set of "eyes." For standard mammograms,
the film is fed into a machine which converts the image into a digital
signal that is then analyzed by the computer. Alternatively, the
technology can be applied to an image captured with digital
mammography. The computer then displays the image on a video screen,
with markers pointing to areas that the radiologist should check
especially closely.
It's not yet clear how useful CAD is. Some doctors find it
helpful, but a recent large study found it did not significantly
improve the accuracy of breast cancer detection. It did, however,
increase the number of women who needed to have breast biopsies.
Further research of this approach is needed.
Magnetic 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 body tissue and by certain diseases.
A computer translates the pattern into a very detailed image of parts
of the body. A contrast material called gadolinium is often
injected into a vein before the scan to better show up details.
MRI scans can take a long time -- often up to an hour. You
have to lie inside a narrow tube, which is confining and may upset
people with claustrophobia (a fear of enclosed spaces). The machine
makes loud buzzing and clicking noises that you may find disturbing.
Some places provide headphones with music to block this out. MRIs are
also expensive, although insurance plans generally pay for them in some
situations, such as once cancer is diagnosed.
Although MRI machines are quite common, they need to be
specially adapted to look at the breast. It's important that MRI scans
of the breast be done on one of these special adapted machines.
MRI can be used along with mammograms for screening women who
have a high risk of developing breast cancer, or it can be used to
better examine suspicious areas found by mammogram. MRI is also used
for women who have been diagnosed with breast cancer to better
determine the actual size of the cancer and to look for any other
cancers in the breast.
Breast Ultrasound
Ultrasound, also known as sonography,
uses high-frequency sound waves to outline a part of the body. For this
test, a small, microphone-like instrument called a transducer is placed
on the skin (which is often first lubricated with oil or ultrasound
gel). It emits sound waves and picks up the echoes as they bounce off
the organs. The echoes are converted by a computer into a black and
white image that is displayed on a computer screen. You are not exposed
to radiation during this test.
Ultrasound has become a valuable tool to use with mammography
because it is widely available and less expensive than other options,
such as MRI. The use of ultrasound instead of mammograms is not
recommended. Usually, breast ultrasound is used to target a specific
area of concern found on the mammogram. Ultrasound also helps
distinguish between cysts (fluid-filled sacs) and solid masses and
between benign and cancerous tumors.
Ultrasound may be most helpful in women with high breast
density (thickness). Clinical trials are now looking at the benefits
and risks of adding screening breast ultrasound to screening mammograms
in women with dense breasts and a higher risk of breast cancer.
Ductogram
This test, also called a galactogram,
is sometimes helpful in determining the cause of nipple discharge. In
this test a fine plastic tube is placed into the opening of the duct in
the nipple. A small amount of contrast medium is injected, which
outlines the shape of the duct on an x-ray image and shows if there is
a mass inside the duct.
Newer Imaging Tests
Newer tests such as scintimammography (technetium sestamibi
scans) and tomosynthesis are not used commonly and are still be
evaluated as to their usefulness. They are described in the section,
"What's
New in Breast Cancer Research and Treatment?"
Other Tests
Nipple Discharge Exam
If you are having 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 milky or clear green in color, 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 causes.
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 more likely to be 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, because 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.
Biopsy
A biopsy is done when mammograms, other imaging tests, 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.
During a biopsy, the doctor removes a tissue sample to be looked at
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 disadvantages. 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.
Fine Needle Aspiration Biopsy
(FNAB)
In an FNA biopsy, the doctor uses a very thin needle attached
to a syringe to withdraw (aspirate) a small amount of tissue from a
suspicious area, which is then looked at under a microscope. The needle
used for FNAB is thinner than the ones used for blood tests.
If the area to be biopsied can be felt, the needle can be
guided into the area of the breast change while the doctor is feeling
(palpating) it.
If the lump can't be felt easily, the doctor might use
ultrasound to watch the needle on a screen as it moves toward and into
the mass. Or the doctor may use a method called stereotactic needle
biopsy to guide the needle. For stereotactic needle biopsy, computers
map the exact location of the mass using mammograms taken from 2
angles, which helps the doctor guide 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 look at
the biopsy tissue or fluid under a microscope to determine if it is
cancerous.
A fine needle aspiration biopsy can sometimes miss a cancer if
the needle is not placed among the cancer cells. 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 removed.
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 (where you are awake but the area is numbed) in
an outpatient setting.
Larger core
biopsies: Two newer 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 hollow probe is inserted
through the incision into the abnormal area of breast tissue. A
cylinder of tissue is then suctioned in through a hole in the side the
probe, and 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 an even larger cylinder of abnormal tissue. It usually requires
a few stitches afterward.
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.
Surgical Biopsy
Sometimes, surgery is needed to remove all or part of the lump
for microscopic examination. An excisional biopsy
removes the entire
mass or abnormal area, 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 (where
you are awake, but your breast is numb). You may also be given medicine
to make you drowsy.
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 want to get a second opinion before deciding on what
treatment is best for you.
Lymph Node Dissection and
Sentinel Lymph Node Biopsy
These procedures are done specifically to look for cancer in
the lymph nodes. They are described in more detail in the section, "How
Is Breast Cancer Treated?"
Laboratory Examination of Breast
Cancer Tissue
Once breast tissue samples have been obtained from a biopsy,
they are looked at in the lab to determine whether breast cancer is
present and if so, what type it is. Other lab tests can help determine
how quickly it is likely to grow and (to some extent) what treatments
are likely to be effective.
Type of Breast Cancer
The tissue removed during the biopsy is first looked at under
a microscope to see if cancer is present and whether it 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 (such as 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 that tend to have a more favorable outlook.
Breast Cancer Grade
A pathologist also assigns a grade to the
cancer, which is
based on how closely the biopsy sample resembles normal breast tissue.
The grade helps predict the patient's prognosis. 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 to spread.
Histologic tumor grade (sometimes called
the 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
small tubules.
- Grade 2 (moderately
differentiated) cancers have
features between grades 1 and 3.
- Grade 3 (poorly
differentiated)
cancers, the highest grade, lack normal features and tend to grow and
spread more aggressively.
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.
Ductal carcinoma in situ (DCIS) is sometimes given a nuclear
grade, which describes how abnormal the cancer cells
appear. The
presence or absence of necrosis
(areas of dead or degenerating cancer
cells), which might indicate a more aggressive cancer, is also noted.
Other factors important in determining the prognosis for DCIS include
the surgical margin
(how close the cancer is to the edge of the
lumpectomy specimen) and the size (amount of breast tissue affected by
DCIS). In situ cancers with high nuclear grade, necrosis, cancer at or
near the edge of the lumpectomy sample, and large areas of DCIS are
more likely to come back after lumpectomy.
Estrogen and Progesterone
Receptor Status
Receptors are proteins on the outside surfaces of cells that
can attach to certain substances, such as hormones, that circulate in
the blood. Normal breast cells and some breast cancer cells have
receptors that attach to estrogen and progesterone. These 2 hormones
often play an important role in both the growth and treatment of breast
cancer.
An important step in evaluating a breast cancer is to test a
portion of the cancer removed during the biopsy or initial surgery for
the presence of estrogen and progesterone receptors. Cancer cells may
contain neither, one, or both of these receptors. Breast cancers that
contain estrogen receptors are often referred to as "ER-positive"
cancers, while those containing progesterone receptors are called
"PR-positive" cancers. Women with hormone receptor-positive cancers
tend to have a better prognosis and are much more likely to respond to
hormone therapy than women with cancers without these receptors.
All breast cancers, with the exception of lobular carcinoma in
situ (LCIS), should be tested for hormone receptors at the time of the
breast biopsy or surgery. About 2 out of 3 breast cancers contain at
least one of these receptors. This percentage is higher in older women
than in younger ones.
HER2/neu Status
About 1 out of 5 breast cancers have too much of a
growth-promoting protein called HER2/neu. This protein is made by cells
under the instruction of the HER2/neu gene. Normally, we have 2 copies
of the HER2/neu gene in every cell in our bodies. Tumors with increased
levels of HER-2/neu are referred to as "HER2-positive."
In women with HER2-positive breast cancers, there are too many
copies of the HER2/neu gene (known as gene amplification), resulting in
greater than normal amounts of the HER2/neu protein. These cancers tend
to grow and spread more aggressively than other breast cancers.
HER2/neu testing should be performed on all newly diagnosed
breast cancers. Testing of the biopsy sample may be done in two ways:
- immunohistochemistry:
In this test, special antibodies that identify
the HER2/neu protein are applied to the sample, which cause cells to
change color if many copies are present. This color change can be seen
under a microscope.
- fluorescent
in situ hybridization (FISH): This test uses pieces of
DNA that identify copies of the HER2/neu gene, which can be counted
under a microscope.
Many breast cancer specialists feel the FISH test is more
accurate than the immunohistochemistry test.
HER2-positive cancers can be treated with drugs that target
the HER2/neu protein, such as trastuzumab (Herceptin) and lapatinib
(Tykerb). See the section, "How Is Breast Cancer Treated?" for more
information on these drugs.
Tests of Ploidy and Cell
Proliferation Rate
The ploidy
of cancer cells refers to the amount of DNA they
contain. If there's a normal amount of DNA in the cells, they are said
to be diploid.
If the amount is abnormal, then the cells are described
as aneuploid.
Although tests of ploidy may help determine prognosis,
they rarely change treatment and are considered optional. They are not
usually recommended as part of a routine breast cancer work-up.
Different methods can be used to measure ploidy:
- Flow cytometry
uses lasers and computers to measure the amount of DNA
in cancer cells suspended in liquid as they flow past the laser
beam.
- Image
cytometry uses computers to analyze digital images of the
cells
from a microscope slide.
Flow cytometry can also measure the S-phase fraction,
which is
the percentage of cells in a sample that are replicating (copying)
their DNA. DNA replication means that the cell is getting ready to
divide into 2 new cells. The rate of cancer cell division can also be
estimated by a Ki-67 test,
which identifies cells in the S-phase, as
well as cells getting ready to replicate DNA, cells that have just
completed DNA replication, and cells in the process of dividing. A high
S-phase fraction or Ki-67 labeling index means that the cancer cells
are dividing more rapidly, which indicates a more aggressive cancer.
Tests of Gene Patterns
Researchers have found that looking at the patterns of a
number of genes at the same time can help predict whether or not an
early stage breast cancer is likely to come back after initial
treatment. This can help when deciding whether additional (adjuvant)
treatment such as chemotherapy might be helpful in women with an
estrogen receptor-positive breast cancer who are going to be taking a
hormone therapy such as tamoxifen after initial surgical treatment. Two
such tests (Oncotype DXTM and MammaPrint®), which look at different
sets of genes, are now available. While some doctors are using them to
make decisions as to whether or not to offer chemotherapy, others are
waiting for more research to prove they are helpful. Large clinical
trials of these tests are now under way.
Revised: 09/13/2007
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