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 DX^TM 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.