The goals of breast cancer testing are to identify genetic risk in high risk women, 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 person over time to detect and address any cancer recurrences. The table below summarizes various breast cancer tests. The tissue samples required for some of the tests may involve a needle biopsy, in which cells from the breast are aspirated through a needle into a syringe, or by surgically removing some breast tissue or a tumor (open biopsy). Detailed discussions of the tests follow the table.
Tests for Breast Cancer
|Mammogram||Highly-sensitive digital X-ray technology that may detect small lumps that otherwise would not be detected through self-exam.||N/A|
|BRCA1 / BRCA2||Genetic markers, if present, suggest an 80% likelihood of breast cancer occurrence.||Blood|
|HER2/neu||A test for specific proteins; tumors with increased levels may respond well to a medication called Herceptin®.||Tissue|
|HER2 (blood)||After an initial diagnosis of metastatic breast cancer is made, this blood test may be performed and, if the initial level is greater than 15 ng/mL, then the test may be used to monitor treatment.||Blood|
|Increased levels suggest a good response to hormonal therapy. Hormonal therapy is not the same as hormone replacement therapy (HRT) and presence of these receptors does not indicate that HRT caused the cancer.||Tissue|
|CA15-3/ CA27.29||Elevated blood levels of cancer antigens may indicate recurrence of cancer.||Blood|
|Oncotype DX®||May assist in determining risk of recurrence and predict who will benefit from hormone therapy or chemotherapy.||Tissue|
|MammaPrint®||May assist in determining whether a woman is at risk of recurrence of cancer, to help guide treatment.||Tissue|
Laboratory tests for breast cancer can be broken down into groups, based on the purpose of testing:
- To determine genetic risk in high risk women: blood testing for mutations that may be present in the BRCA1 and BRCA2 genes
- 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 HER2/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
Some tests for breast cancer are performed on the woman's blood; others are done on a sample of cells or the tumor tissue.
BRCA1 or BRCA2 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 person 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.
Diangosis: cytology and surgical pathology
When a radiologist detects a suspicious area, such as hardened tissue (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, shape, and appearance of cell nuclei and evidence of increased cell division. Malignant cells can also distory the normal arrangement of cells within breast tissue. 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 aspiration evaluations 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.
If the pathologist's diagnosis is breast cancer, there are several tests that may be performed on the tissue cancer cells. The results of these tests provide a prognosis and help the oncologist (cancer specialist) guide the woman's treatment. The most useful of these are HER-2/neu and estrogen and progesterone receptors.
- HER2/neu is an oncogene associated with cell growth. Normal epithelial cells contain two copies of the HER2/neu gene and produce low levels of the HER2 protein on the surface of their cells. In about 20-30% of invasive breast cancers, the HER2/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. Women with amplified HER2/neu gene respond well to Herceptin® and have a good prognosis.
- Estrogen and progesterone receptor (ER and PR) status are important prognostic markers. Breast cancer cells that have estrogen and/or progesterone receptors can bind estrogen and progesterone. These female hormones promote cell growth and can "feed" ER- and PR-positive cancers. The higher the percentage of cancer cells that are positive, as well as the greater the intensity (the number of receptors per cell), the better the prognosis. This is because hormone-dependant cancers frequently respond well to hormonal therapy.
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 person for breast cancer recurrence. It is not used as a screen for breast cancer but can be used to follow it in some women once it has been diagnosed.
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 2011 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:
- Oncotype DX® – ASCO indicates that this test, which measures 21 genes, can be used to predict risk of cancer recurrence in those who have been newly diagnosed with early breast cancer, have cancer-negative lymph nodes, have estrogen receptor positive tumors, and are taking the drug tamoxifen.
- MammaPrint® test – in use in Europe and recently cleared by the FDA for use in the U.S. This test evaluates gene activity patterns in 70 tumor genes. It may be used to help predict whether a breast cancer will recur and/or metastasize in women who have early stage cancer, are under the age of 61, and have cancer-negative lymph nodes.
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 HER2/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.
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).