Breast Cancer

The goals of breast cancer testing are to identify genetic risk in high risk patients, detect and diagnose breast cancer in its earliest stages, determine how far it has spread, evaluate the cancer’s characteristics in order to guide treatment, monitor the effectiveness of treatment, and monitor the woman over time to detect and address any cancer recurrences. The table below summarizes various breast cancer tests. Detailed discussions of the tests follow the table.

Tests for Breast Cancer

Laboratory Tests

Laboratory tests for breast cancer can be broken down into groups, based on the purpose of testing:

• To diagnose: cytology - a microscopic examination of tumor cells obtained through fine needle aspiration and surgical pathology - a microscopic examination of tissue sampling via biopsy
• To determine treatment options: evaluation of the tumor's HER-2/neu gene amplification status and estrogen and progesterone receptor status
• To monitor treatment and for recurrence: measurement of CA 15-3 or CA 27.29 in the blood
• To determine genetic risk in high risk patients: blood testing for mutations that may be present in the BRCA-1 and BRCA-2 genes

Some tests for breast cancer are performed on the patient’s blood; others are done on a sample of cells or the tumor tissue.

Cytology and surgical pathology

When a radiologist detects a suspicious area, such as calcifications or a non-palpable mass on a mammogram, or if a lump has been found during a clinical or self-exam (see Non-Laboratory Tests below), a doctor will frequently order a needle or surgical biopsy or a fine needle aspiration. In each case, a small sample of tissue is taken from the suspicious area of the breast so that a pathologist can examine the cells microscopically for signs of cancer. This pathological examination is done to determine whether the lesion is benign or malignant.

Malignant cells show changes or deviations from normal cells. Signs include changes in the size of cell nuclei and evidence of increased cell division. Pathologists can diagnose cancer based upon the observed changes, determine how abnormal the cells appear, and see whether there is a single type of change or a mixture of changes. These results help guide breast cancer treatment.

Needle aspirations are limited due to the small sample that is obtained. A tissue biopsy is needed to determine if a cancer is early stage or invasive. When a breast cancer is surgically removed (see Treatment), cells from the tumor and sometimes from adjacent tissue and lymph nodes are examined by the pathologist to help determine how far the cancer has spread.

Tests performed on tumor tissue

If the pathologist’s diagnosis is breast cancer, there are several tests that may be performed on the cancer cells. The results of these tests provide a prognosis and help the oncologist (cancer specialist) guide the patient’s treatment. The most useful of these are HER-2/neu and estrogen and progesterone receptors.

• Her-2/neu is an oncogene . It codes for a receptor for a particular growth factor that causes cells to grow. Normal epithelial cells contain two copies of the Her-2/neu gene and produce low levels of the Her-2 protein on the surface of their cells. In about 20-30% of invasive breast cancers, the Her-2/neu gene is amplified and its protein is over-expressed. These tumors are susceptible to treatment that specifically binds to this over-expressed protein. The chemotherapeutic agent Herceptin (Tastuzumab) blocks the protein receptors, inhibiting continued replication and tumor growth. Patients with amplified Her-2/neu gene respond well to Herceptin and have a good prognosis.
• Estrogen and progesterone receptor status are important prognostic markers in breast cancer. The higher the percentage of overall cells positive, as well as the greater the intensity, the better the prognosis. Estrogen and/or progesterone receptor positivity in breast cancer cells indicates sensitivity to hormones. The patient may be a good candidate for anti-hormone therapy.

Blood tests

Blood tests may be used to help determine whether or not the tumor is responding to therapy or if it has recurred. Some may be ordered on women who are at a high risk of developing breast cancer to determine whether their risk has a genetic component.

• CA15-3 (or CA 27.29) is a tumor marker that may be ordered at intervals after treatment to help monitor a patient for breast cancer recurrence. It is not used as a screen for breast cancer but can be used to follow it in some patients once it has been diagnosed.
• BRCA-1 or BRCA-2 gene mutation – Women who are at high risk because of a personal or strong family history of early onset breast cancer or ovarian cancer can find out if they have a BRCA gene mutation. A mutation in either gene indicates that the patient is at significantly higher lifetime risk (up to 80%) for developing the disease. It is important to remember, however, that only about 5% to 10% of breast cancer cases occur in women with a BRCA gene mutation. Genetic counseling should be considered both before testing takes place and after receiving positive test results.

Other tests

There are several tests available, and many others being researched, that evaluate large numbers of genetic patterns in breast cancer tumor tissue. These tests are being investigated as predictive tests for the recurrence of breast cancer and therapy outcome. The American Society of Clinical Oncology (ASCO) mentioned several of them in its recent “2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer” and some have been included in the National Comprehensive Cancer Network’s 2008 Breast Cancer Treatment Guidelines. In most cases, the tests were deemed promising, but data to support their routine clinical use were still thought to be insufficient. Examples of tests being ordered by some doctors include:

There are additional tests that may be used in some breast cancer cases, such as DNA ploidy, Ki-67, or other proliferation markers. However, most authorities believe that HER-2/neu, estrogen and progesterone receptor status are the most important to evaluate first. The other tests do not have therapeutic implications and, when compared with grade and stage of the disease, are not independently significant with respect to prognosis. Some medical centers use these tests for additional information in evaluating patients, making it important to discuss the value of these tests with your cancer management team.

Non-Laboratory Tests

In addition to laboratory tests, there are non-laboratory tests that are equally important. These include:

• Mammography is widely recommended as a screening tool. A screening mammogram uses X-ray technology to produce an image of the breasts and can reveal breast cancer up to two years before a lump is large enough to be felt during a clinical or self-exam.
• Newer technologies, such as digital mammography and computer-aided detection, may yield a clearer image than a mammography in some cases. In particular, younger women, whose breast tissue is often too dense to show tumors clearly on the X-ray film used for a standard mammogram, may benefit from ultrasound exams or magnetic resonance imaging (MRI).
• Ductal lavage may also be used as a screening tool, particularly for women at high risk for developing the disease. In this procedure, a doctor extracts cells via a tiny tube inserted through the patient's nipple. Those cells are then examined for signs of cancer.

For more information on mammography and other imaging technologies, go to the National Cancer Institute’s website or the College of American Patholgists website.