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 mutations, if present, suggest a likelihood of breast cancer occurrence as high as 80%.||Blood|
|HER2/neu||A test for the overexpression of HER2 proteins or the amplification of the gene that codes for the protein; tumors that are positive may respond well to a medication that targets HER2, such as 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, 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||This test measures a specific cancer antigen. Elevated blood levels may indicate recurrence of cancer.||Blood|
|Oncotype DX®||A genetic test that may assist in determining risk of recurrence and predict who will benefit from hormone therapy or chemotherapy.||Tissue|
|MammaPrint®||A genetic test that 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.
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 (between 50-80%) 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.
Diagnosis: 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 health practitioner 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 distort 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 often 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.
For more on this, see the article on Anatomic Pathology.
Determine treatment options:
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. Drugs that target HER2 include, for example, trastuzumab (Herceptin®) and lapatinib. Women with amplified HER2/neu gene respond well to these drugs and have a good prognosis.
- Estrogen and progesterone receptor (ER and PR) status are important for predicting the course of the disease and helping to guide treatment. 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 that blocks estrogen or lowers estrogen levels.
Breast cancer cells that are negative for HER2/neu amplification and negative for estrogen and progesterone receptors are called "triple-negative." This type of breast cancer occurs more often in younger women and in women of African or Hispanic descent. Women with triple negative breast cancer may be predisposed to BRCA mutations.
Triple negative breast cancers tend to grow and spread more quickly than other types and have a worse prognosis. Because the cells do not have amplified HER2/neu, they will not respond to treatment with trastuzumab (Herceptin®) or lapatinib. Likewise, they do not have receptors for estrogen and progesterone and cannot be treated with therapy that blocks the hormones. However, they may be treated with other types of chemotherapy.
Cancer antigen 15-3 (CA 15-3) – this is a protein that is produced by normal breast cells. There is an increased production of CA 15-3 and the related cancer antigen 27.29 in many women with breast cancer. CA 15-3 does not cause cancer. Rather, the protein is shed by tumor cells and enters the blood, making it useful as a tumor marker to follow the course of the cancer. CA 15-3 is elevated in only about 10% of women with early localized breast cancer but is elevated in about 80% of those with metastatic breast cancer. Blood tests for CA 15-3 (or CA 27.29) may be ordered at intervals after treatment to help monitor a woman for breast cancer recurrence. They are not used as screens 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 "2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer." In most cases, the tests were deemed promising, but data to support their routine clinical use were still thought to be insufficient. Examples of these tests being ordered by some health practitioners 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. Oncotype DX is included in the National Comprehensive Cancer Network's 2015 Breast Cancer Treatment Guidelines.
- MammaPrint® test – in use in Europe and 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 a cancer management team.
In addition to laboratory tests, there are non-laboratory tests that are equally important. These include the following:
- 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).