Breast Cancer

Genomic & Genetic Testing

Diagnosing and treating breast cancer has changed dramatically in recent years due to the increasing use of genomic and genetic testing. These tests help a doctor pick the treatment course best suited for a specific type of breast cancer. This emphasis on specialized testing is helping to drive treatment choices, providing more personalized therapy options.

Doctors now understand that not all breast cancers are alike. In fact, breast cancer is a complex disease characterized by mutations in genes and proteins that cause cells to grow out of control. Diagnosing any breast cancer involves blood tests, imaging tests and a biopsy, but the definitive factor to determining a breast cancer diagnosis begins with genomic testing of the biopsy sample after surgery.

Understanding Genomic Testing

Genomic testing may reveal mutations and biomarkers that could indicate the cancer’s subtype and behavior, how aggressive it might be and how likely it is to metastasize (spread). Biomarkers are substances such as genes or molecules that can be measured in the blood, plasma, urine, cerebrospinal fluid or other body fluids or tissues. They are produced by cancer cells or other cells of the body in response to cancer.

The three biomarkers routinely tested for during the breast cancer diagnostic process are estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). Knowing the status of these three biomarkers helps your doctor know whether you will benefit from chemotherapy and/or hormone therapy (also called endocrine therapy). If the cancer is driven by estrogen or progesterone, hormone therapy may be used to lower the risk of a recurrence. If a HER2 mutation is driving the cancer, drugs that target HER2 may be recommended.

The genomic tests can also be performed during treatment or if the cancer returns to identify different mutations than before that may affect treatment options. The development of a new tumor in the breast will also require testing because it may have different mutations than the first tumor.

Other genomic tests may be performed to evaluate and predict a possible recurrence. Tests provide a score that may be useful in determining whether hormone therapy or chemotherapy is recommended to prevent a recurrence. These tests are multi-gene panels, which are used to determine whether adjuvant or extended adjuvant chemotherapy should be used.

Types of Tests

A variety of tests may be used for genomic testing (see Table 1). Some of the tests are known by specific names and are used to find different types of information about your breast cancer.

Your doctor will decide which test provides the kind of information that will aid in treatment. Following are some of the types used for genomic testing.

  • Immunohistochemistry (IHC) tests for certain antigens (markers) and may also be used to determine the difference between cancer subtypes. In breast cancer, it is used to measure the amount of HER2 proteins on the surface of breast cancer cells. Based on the number of proteins, a score is given to determine whether the cancer is HER2+. It uses a scale of 0 to 3+, with 0 meaning the cancer is HER2- and 3+ meaning the cancer is HER2+. If the score is 2, another test, such as the fluorescence in situ hybridization (FISH) test, may be used. Results may also be sent to another cancer center for a second opinion. The IHC test is typically performed first because the results can be returned quicker, and a 0 or 3+ usually requires no further testing.
  • FISH testing uses fluorescent dye that attaches to certain pieces of DNA in a tissue sample. It looks at genes or chromosomes in cells and tissues and identifies where a specific gene is located on a chromosome, how many copies of the gene are present and any chromosome abnormalities. For breast cancer, this test evaluates HER2 gene amplification. It is performed if the results of the IHC testing were inconclusive or in doubt. The results take longer to return than for IHC testing, but this test is considered more definitive.
  • Microarray testing generates a genetic profile for a given tissue sample that reflects the activity of thousands of genes and helps to identify subtypes.
  • Polymerase chain reaction (PCR) looks for certain changes in a gene or chromosome.
  • Reverse transcription PCR (RT-PCR) is used to look for activation of certain genes that may help diagnose cancer.

The Role of Genetic Testing

Though genomic testing is used to determine the status of ER, PR and HER2, genetic testing may also be performed to identify the BReast CAncer 1 (BRCA1) and BReast CAncer 2 (BRCA2) genes, the most commonly inherited mutated genes known to cause breast cancer.

Identifying inherited mutations allows people at an increased risk to be monitored more closely for the development of cancer. A family history of a certain cancer may prompt you to be tested to see whether you carry a mutated gene. The test to see whether you have an inherited mutation is usually performed on saliva or blood. Having an inherited mutation does not mean you will automatically develop cancer; it only means the risk is increased.

The following risk factors may indicate that you have inherited an abnormal gene:

  • Family history of cancer
  • Cancer at an early age
  • Multiple cancers in one relative
  • History of rare cancers
  • Certain ancestry, such as Ashkenazi Jewish heritage

These tests are generally ordered by a doctor or other health care provider if there is a concern that you may have an inherited risk of cancer. Doctors may test for one gene or a small number of genes – which is called single/limited gene panel testing – or many genes. Typically, the blood or saliva sample is collected and sent to a laboratory for testing.

Though some genetic tests are available to purchase without a doctor’s involvement, they are not recommended for a person who may have cancer. The sensitivity of these tests is unknown compared to those used by doctors and designated laboratories, and the tests may not screen for all the possible genes and mutations for a particular cancer. The laboratories doctors use are regulated by the Clinical Laboratory Improvements Amendments program to meet standards for accuracy and reliability.

Getting genetic testing is a decision that can affect your entire family. Knowing and sharing the information could help them be screened and monitored closely if they have a gene mutation associated with cancer. Prevention and detection offer the best chance of a successful treatment outcome.

The results may be complicated and difficult to interpret. A genetic counselor can guide you through the testing process so you understand what the results mean for you, your family members and their future health. Family members may be offered genetic testing if a mutation is found.

Special training enables a genetic counselor to provide guidance to you and your family members before and after you have genetic testing. The genetic counselor will discuss your medical history and cancer screening history, your family’s cancer history, the possibility of an inherited cancer risk, the benefits and limitations of genetic testing, and current laws regarding the privacy of genetic information. The counselor can also help find out whether your health insurance will pay for the cost of the test.

Ask your nurse navigator for a referral to a genetic counselor.

Table 1. Some Types of Genomic Testing Used for Breast Cancer

Genomic Test Type of Test Reason for Test Indications
21-Gene Recurrence Score (Oncotype DX) Quantitative polymerase chain reaction Determine the use of adjuvant chemotherapy in ER+, HER2- breast cancer with or without lymph node involvement Only patients with high-risk recurrence scores may benefit from chemotherapy
70-Gene Breast Cancer Recurrence Assay (MammaPrint) Algorithm on whole-genome expression array Determine prognosis for Stage I and II HER2- invasive breast cancer regardless of ER or HER2 status that has spread to 3 or fewer lymph nodes Prognostic tool for early-stage breast cancer; high risk score indicates a benefit from chemotherapy
Breast Cancer Index Anti-apoptotic homeobox B13-to-interleukin 17B receptor expression ratio (H:I ratio), representing a 2-gene ratio, and the Molecular Grade Index, representing five proliferation genes Determines probability of benefiting from extended adjuvant endocrine therapy in post-menopausal patients with ER+, lymph node negative disease A high H:I ratio in ER+ and positive lymph node involvement breast cancer indicates benefit from extended adjuvant endocrine therapy
EndoPredict Reverse transcriptase polymerase chain reaction (RT-PCR) Used to calculate a comprehensive risk score. Identifies patients with ER+, HER2- tumors with 3 or fewer lymph nodes affected and who have a low risk for late recurrence without adjuvant chemotherapy Guides treatment decisions on whether to use chemotherapy and anti-hormonal therapy
Ki-67 Assay, including ICH4, PEPI Immunohistochemical staining An estimate of the rate of growth (proliferation) that is helpful in selecting the type of chemotherapy given High Ki-67 expression indicates higher tumor growth rate
PAM50 Microarray and quantitative reverse transcriptase Measures expression levels of 50 genes, defines subtype, provides a risk category and creates a risk of recurrence score Adds prognostic value to the characteristics of the tumor