Breast Cancer Work-Up

Evaluating a Breast Lump or Abnormal Mammogram Finding

An evaluation of a breast lump or an abnormal mammogram finding includes a thorough medical history, a physical examination, and breast imaging (such as x-rays). A biopsy is needed for a suspicious finding, though often these suspicious areas prove to be benign (not cancer). If cancer is found, other x-rays and blood tests are needed. Exactly which tests are helpful depends on the type of cancer, and if and where it has spread. The following sections provide a summary of the steps, tests, and types of biopsy that may be suggested.

Doctor Visit and Examination

A women’s first step in having a new breast lump, symptom, or change on a mammogram evaluated is to meet with her doctor. The doctor will take a medical history which includes asking a series of questions about symptoms and factors that may be related to breast cancer risk (such as family history of cancer). The physical exam should include a general examination of the woman’s body as well as careful examination of her breasts (called palpation). The doctor will examine:

• the breasts, including texture, size, relationship to skin and chest muscles, and the presence of lumps or masses
• the nipples and skin of the breasts
• lymph nodes under the armpit and above the collarbone
• other organs to check for obvious spread of breast cancer and to help evaluate the general condition of the woman’s health

Breast Imaging

After completing the physical exam and medical history, the doctor will recommend tests to look at the breast, beginning with a mammogram (unless this has already been done or if the woman is very young).

Women with a lump in the breast, other suspicious symptoms, or with a change found on a screening mammogram, will often have a procedure called a diagnostic mammogram. A diagnostic mammogram includes more mammogram pictures of the area of concern to get more information about the size and character of the area. A breast ultrasound or sonogram also may be done. The ultrasound uses high frequency sound waves to further evaluate a lump or mammogram finding. Most importantly, ultrasound helps determine if the area of concern is a fluid-filled simple cyst, which is usually not cancer, or is solid tissue that may be cancer.

Some women may have a breast magnetic resonance imaging (MRI)procedure in addition to a diagnostic mammogram and ultrasound. However, a breast MRI should not be used in place of standard mammography and ultrasound. Furthermore, breast MRI is not routinely used to diagnose breast cancer and is not needed for women with breasts that can be adequately evaluated with mammography and ultrasound. (See discussion of MRI below.)

Breast Biopsy

If a woman or her doctor finds a suspicious breast lump, or if imaging studies show a suspicious area, the woman must have a biopsy. This procedure takes a tissue sample to be examined under the microscope to see if cancer is present.

There are several different types of breast biopsies. Biopsy may be done with a needle, where the doctor removes a piece of breast tissue by placing a needle through the skin into the breast. For a surgical biopsy a surgeon uses a scalpel to cut through the skin and remove a larger piece of the suspicious breast tissue. Each type of biopsy has advantages and disadvantages. The type of biopsy procedure used is tailored to each woman’s situation and the experience of her health care team.

In most cases, a needle biopsy is preferred over a surgical biopsy as the first step in making a cancer diagnosis. A needle biopsy provides a diagnosis quickly and with little discomfort. In addition, it gives the woman a chance to discuss treatment options with her doctor before any surgery is done. Sometimes a surgical biopsy may still be needed to remove all or part of a lump after a needle biopsy has been done. In some patients it may be necessary to do a surgical biopsy instead of needle biopsy.

Several types of needle biopsies are used to diagnosis breast cancer. The most common is a core needle biopsy that removes a small cylinder of tissue. A suction device can also be used to remove breast tissue, which may be useful if multiple mammogram abnormalities, such as calcifications, are clustered together. Another type of biopsy is fine needle aspiration biopsy (FNA). FNA uses a smaller needle than a core biopsy and removes a small amount of cells for evaluation under the microscope. FNA also is used to remove fluid from a suspicious cyst.

If the lump can be felt, a doctor can do a core needle or FNA biopsy in the office, without the aid of breast x-rays to guide the needle. If a lump cannot be felt easily, ultrasound or mammograms can be used to guide the needle during the biopsy. The mammogram-directed technique is called stereotactic needle biopsy. In this procedure, a computerized view of the mammogram helps the doctor guide the tip of the needle to the right spot. Ultrasound can be used in the same way to guide the needle. The choice between a mammogram directed stereotactic needle biopsy and ultrasound guided biopsy depends on the type and location of the suspicious area, as well as the experience and preference of the doctor.

Some patients need a surgical (excisional) biopsy. The surgeon generally removes the entire lump or suspicious area and includes a zone of surrounding normal appearing breast tissue called a margin. If the tumor cannot be felt, then the mammogram or ultrasound is used to guide the surgeon through a technique called wire localization. After numbing the area with a local anesthetic, x-ray or ultrasound pictures are used to guide a small hollow needle to the abnormal spot in the breast. A thin wire is inserted through the center of the needle, the needle is removed, and the wire used to guide the surgeon to the right spot.

Most breast biopsies cause little discomfort. Only local anesthesia (numbing of the skin) is necessary for needle biopsies. For surgical biopsies, most surgeons use a local anesthetic plus some medicines injected into a vein to make the patient drowsy. A general anesthetic (using drugs to make the patient sleep) is not needed for most breast biopsies.

Tissue examination and pathology report

After a breast biopsy, the biopsy tissue is sent to a pathology lab where a doctor trained to diagnose cancer (a pathologist) examines it under the microscope. This process may take several days. This examination of the breast tissue determines if cancer is present.

Your doctor should give you your pathology results. You can ask for a copy of your pathology report and to have it explained carefully to you. If you want, you can get a second opinion of the pathology of your tissue by having the microscope slides of your tissue sent to a consulting breast pathologist at an NCCN cancer center or other laboratory suggested by your doctor.

Other Tests After Cancer Has Been Diagnosed

If the breast biopsy results show that cancer is present, the doctor may order other tests to find out if the cancer has spread and to help determine the best treatment. For most women with breast cancer, extensive testing is of no benefit and is not necessary. There is no test that can completely reassure you that the cancer has not spread. The NCCN Guidelines describe which tests are needed based on the extent (spread) of the cancer, and on the results of the history and physical exam. These tests use x-rays, magnetic fields, or radioactive substances to create pictures of the inside of the body to look at the extent of the cancer. Tests that may be done include:

Chest x-ray
All women with invasive breast cancer should have a chest x-ray before surgery and to see if there is evidence that the breast cancer has spread to the lungs.

Bone scan
This may provide information about spread of breast cancer to the bone. However, many changes that show up on a bone scan are not cancer. Unless there are symptoms of spread to the bone, including new pains or changes on blood tests, a bone scan is not recommended except in patients with advanced cancer. To do a bone scan, a small dose of a radioactive substance is injected into your vein. The radioactive substance collects in areas of new bone formation. These areas can be seen on the bone scan picture. Other than the needle stick for the injection, a bone scan is painless.

Computerized tomography (CT) scans
CT scans are done when symptoms or other findings suggest that cancer has spread to other organs. For most women with an early stage breast cancer, a CT scan is not needed. But if the cancer appears to be more advanced, a CT of the abdomen and/or chest may be done to see if the cancer has spread. CT scans take many x-rays of the same part of the body from different angles to provide detailed pictures of internal organs. Except for the injection of intravenous dye, necessary for most patients, this is a painless procedure.

Magnetic resonance imaging (MRI)
MRI scans use radio waves and magnets to produce detailed images of internal organs without any x-rays. MRI is useful in looking at the brain and spinal cord and to look at any suspicious area in the bone. A special MRI procedure called a breast MRI with dedicated breast coils can also be used to look for tumors in the breast. This procedure should only be done by personnel who are highly experienced in the technical details of breast MRI. Also, in order for the results of a breast MRI exam to be useful, they should be interpreted by the personnel at the center where the breast MRI was performed. These people should be working directly with the other medical professionals involved in your care.

Routine MRI’s for all patients with breast cancer are not helpful and are not needed. Situations where a breast MRI can be useful include the following:

• Women who have had a biopsy result showing cancer in the axilla (armpit), but do not show signs of breast cancer when their breasts are examined by a doctor or by mammography.
• Women with a biopsy result showing cancer in the breast who have dense breasts (breasts with a lower amounts of fat compared with other tissues) that can not be fully evaluated with mammography.

Positron emission tomography (PET)
PET scans use a form of sugar (glucose) that contains a radioactive atom. A small amount of the radioactive material is injected into a vein in your arm. After the sugar has been allowed to travel throughout your body you are put into the PET machine where a special camera can detect the radioactivity. Because of the high amount of energy that breast cancer cells use, areas of cancer in the body absorb large amounts of the radioactive sugar. Newer devices combine PET scans and CT scans. PET scans are not routinely recommended for most patients with breast cancer, but may be used to initially evaluate patients with metastatic disease or recurrent breast cancer. PET scans may also be used if results of other tests do not clearly show whether the cancer has spread beyond the breast to other areas of the body.

Blood Tests
Some blood tests are needed to plan surgery, to screen for evidence of cancer spread, and to plan treatment after surgery. These blood tests include:

• Complete blood count (CBC). This determines whether the blood has the correct type and number of blood cells. Abnormal test results could reveal other health problems, including anemia, and could suggest the cancer has spread to the bone marrow. Also, if you receive chemotherapy, doctors repeat this test regularly because chemotherapy often affects the blood forming cells of the bone marrow.
• Blood chemicals and enzyme tests. These tests are done in patients with invasive breast cancer. (They are not needed with in situ cancer.) They can sometimes tell if the cancer has spread to the bone or liver. If these test results are abnormal, your doctor will order imaging tests, such as bone scans or CT scans.

Tumor tests (estrogen receptor, progesterone receptors, and HER-2/neu)
Testing the tumor itself for certain features is an important step in deciding what treatment options are best for your type of cancer. The pathology lab tests the cancer tissue that is removed, either from a biopsy or the final surgery.

Estrogen and Progesterone Receptors: Two hormones in women — estrogen and progesterone — stimulate the growth of normal breast cells and play a role in many breast cancers. Cancer cells respond to these hormones through the estrogen receptors (ER) and progesterone receptors (PR). ER and PR are each cell’s “welcome mat” for these hormones circulating in the blood. The tumor is tested for these hormone receptors in a test called a hormone receptor assay. If a cancer does not have these receptors, it is referred to as hormone receptor-negative (estrogen receptor-negative and progesterone receptor-negative). If the cancer has these receptors, it is referred to as hormone receptor-positive (estrogen receptor-positive and/or progesterone receptor-positive). A cancer can also be just ER-positive or PR-positive.

The hormone receptors are important because cancer cells that are ER- or PR-positive often stop growing if the woman takes drugs that either block the effect of estrogen and progesterone or decrease the body’s levels of estrogen. These drugs also lower the chance that the cancer will come back (recur) and improve the chances of living longer. Most women whose breast cancer is ER-positive or PR-positive will take these drugs as part of their treatment. However, these hormone-active drugs are not effective if the cancer does not contain these receptors.

All breast cancers, with the exception of lobular carcinoma in situ, should be tested for hormone receptors. Each woman should ask her doctor for these test results, and if hormone-like drugs or blocking her own hormones should be part of her treatment.

HER2: About 15-20% of breast cancers have too much of a growth-promoting protein called HER2 and too many copies (more than 2) of the gene that instructs the cells to produce this protein. Tumors with increased levels of HER2 are referred to as “HER2-positive.”

HER2-positive breast cancer tumors tend to grow and spread more rapidly than other breast cancers. Trastuzumab and lapatinib are two available treatments that specifically target HER2-positive tumors and block HER2 from stimulating breast cancer cell growth. (See discussion of targeted therapy.) Recent studies have shown that trastuzumab given after breast cancer surgery for HER2-positive tumors reduces the risk of recurrence when the tumor measures larger than 1 cm in diameter or when the cancer has spread to the lymph nodes. Another very recent study of women with advanced breast cancer has shown lapatinib to be effective in delaying the growth of HER2-positive tumors after trastuzumab has stopped working. Studies also suggest that chemotherapy containing certain drugs (such as doxorubicin or epirubicin) may be especially effective against breast cancers that are HER2-positive.

Certain therapies are effective only for patients with HER2-positive breast cancers and these treatments have potential side effects associated with them. Therefore, accurate testing to determine the HER2 status of a breast cancer tumor is very important, and an incorrect test result can have serious consequences. The HER2 status of a tumor can be tested using either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) testing. IHC testing is used to show how much of the HER2 protein is on the surface of the cancer cells. FISH testing is used to provide information related to the number of copies of the HER2 gene in the tumor cells. There is more than one type of IHC or FISH test which has been shown to give accurate HER2 test results. However, the laboratory doing the test must be an accredited laboratory with quality control procedures in place to ensure that the testing is done properly. Additional testing of the tumor sample should be done if the HER2 test score falls between a “negative” and a “positive” test result (for example, a sample initially tested by IHC would be retested by FISH). In the event that a particular laboratory does not meet quality assurance standards for testing, the tumor sample should be sent to another laboratory that meets these standards. If your doctor does not know whether a particular laboratory meets these criteria, you can contact the head of the laboratory in question (often a pathologist) for this information.

Analysis of Gene Profiles of Tumors
Treatment decisions today are primarily based on hormone receptor tumor status, HER2 status, appearance of the cancer under the microscope, size of the breast cancer, and extent of spread of the breast cancer. Recently, there has been interest in looking at specific sets of genes (gene profiles) within breast cancer tumor cells to see if women with breast cancer that has not spread to the lymph nodes can be identified as having either a more favorable outlook (a low chance of cancer recurrence), a less favorable outlook (a higher chance of cancer recurrence), or an outlook somewhere between the two (an intermediate chance of cancer recurrence). This type of information has the potential to be particularly helpful when a patient and her doctor are making treatment decisions. In the future it could help determine whether the patient may be likely to benefit from chemotherapy (for example, patients with a poorer outlook would be more likely to benefit from chemotherapy) or whether a patient is likely to do well without chemotherapy. At the present time more studies are needed on this new way to evaluate cancer cells before specific treatment recommendations can be made based upon these types of test results.

Breast cancer grade
Pathologists look at breast cancer cells under a microscope and determine how much they look like normal breast tissue. This is called the grade of the tumor. Cancers that closely resemble normal breast tissue get a lower number grade and tend to grow and spread more slowly. In general, a lower grade number indicates a cancer that is slightly less likely to spread, and a higher number indicates a cancer that is slightly more likely to spread.

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). A low grade (Grade 1) cancer may also be called “well-differentiated” because it more closely resembles normal breast cells. Similarly, a high grade tumor (Grade 3) may also be called “poorly differentiated,” since the cells have lost their resemblance to normal breast cells. A moderate grade (Grade 2) cancer is in between low grade and high grade.

The tumor grade is most important in patients who have small tumors with no lymph node involvement. Patients with well-differentiated tumors may require no further treatment, while patients with moderately or poorly differentiated tumors usually receive additional hormonal therapy or chemotherapy.

Ductal carcinoma in situ (DCIS) is graded in a different way. DCIS is given a nuclear grade, which describes how abnormal the part of the cancer cells that contain the genetic material appears. Sometimes other features of DCIS are also used by the pathologist to determine the grade.

TYPES OF BREAST CANCER

STAGES OF BREAST CANCER

For more information on these treatment guidelines, or on cancer in general, call the NCCN at 1-888-909-NCCN or the American Cancer Society at 1-800-ACS-2345. Or you can visit these organizations’ web sites at www.cancer.org (ACS) and www.nccn.org (NCCN).

© 2007 by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS). All rights reserved. The information herein may not be reproduced in any form for commercial purposes or downloaded and stored in any information-retrieval system without the express written permission of the NCCN and the ACS. Single copies of each page may be printed out for personal, noncommercial use only.