Diagnosis of Breast Cancer

If screening tests or signs and symptoms suggest breast cancer, 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 mammography has increased the number of breast cancers found before they cause any symptoms, some breast cancers are not found by mammography, either because the test was not done or because even under ideal conditions mammography 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 even before the original tumor in the breast tissue is large enough to be felt.

Medical History and Physical Exam

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.

Imaging Tests to Diagnose Breast Disease

Mammography:

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 examination (see below) finds that the lump is a cyst.

The American Cancer Society believes the use of mammography, clinical breast examination, and breast self-examination, according to the recommendations outlined above, offers women the best opportunity for reducing the breast cancer death rate through early detection. This combined approach is clearly better than any one examination. Without question, breast physical examination without mammography 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 mammography 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 by 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 the duct.

Full-field digital mammography (FFDM):

Full field digital mammography is similar to standard mammography 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 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 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 FFDM and film mammography. It is important to remember that standard film mammography also is effective for these groups of women, and that they should not forego their regular mammogram if digital mammography 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 abnormalities on mammograms. This is done most commonly with screen-film mammography and less often with digital mammography. 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 mammography alone.

Scintimammography:

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 abnormal mammograms.

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 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 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. Also, they 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 standard mammography. However, it is not yet known if the difference between MRI and mammography 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.

Other Tests

Nipple discharge examination:

If you have spontaneous nipple discharge, some of the fluid may be collected and examined 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 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 smear 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 breast cancer. 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, nor have there been any studies to show that this approach prevents the development of breast cancer or death from breast cancer. 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, nor have there been any studies to show that it prevents the development of breast cancer or death from breast cancer.

Biopsy

A biopsy is done when mammograms, ultrasound, or the physical examination finds an 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 distinct 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):

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 abnormality 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 these to determine if they are 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 abnormalities felt by the doctor, as well as smaller ones pinpointed by ultrasound or mammogram. Depending on whether the abnormality 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 in an outpatient setting.

Two new devices can be guided by stereotactic methods and can remove more tissue than a core biopsy. The Mammotome, also known as vacuum-assisted biopsy, suctions tissue into a cylinder that is inserted into the breast tissue. A rotating knife then cuts the tissue samples from the breast. This method usually removes about twice as much tissue as core biopsies. The ABBI method (short for Advanced Breast Biopsy Instrument) uses a rotating circular knife to remove a large cylinder of tissue.

Surgical biopsy:

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 a 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 (due to calcifications, for example) 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 locate 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.

Imaging Tests to Detect Breast Cancer Spread

Chest 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 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 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 (see below) will be needed.

Computed tomography (CT):

The CT scan is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one picture, as does a conventional 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, the patient remains 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 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. 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.

Magnetic 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. Also, you 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.

Positron emission 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 high amounts of the radioactive sugar, because of their high rate of metabolism. 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.

This test can be used as a diagnostic aid to mammography, especially in looking for cancer in axillary lymph nodes. So far, though, most studies show it isn’t very sensitive in finding small deposits of cancer in lymph nodes, although it can find big ones.

Laboratory Examination of Breast Cancer Tissue

Types 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 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.

Grades 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 to spread.

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 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.

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) is also noted.

Some researchers have suggested combining information about the nuclear grade and necrosis with information about 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.

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Estrogen and progesterone receptors:

Receptors are parts 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 play an important role in 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 surgical treatment for the presence of these receptors. Breast cancers that contain estrogen and progesterone receptors are often referred to as ER-positive and PR-positive tumors, or simply hormone receptor positive. Women with these cancers tend to have a better prognosis and are much more likely to respond to hormone therapy than women with cancers without these receptors . About two thirds of breast cancers contain estrogen receptors. This percent is higher in older women and lower in younger ones.

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