Next-generation sequencing (NGS) tests

Next-generation sequencing (NGS) is a testing technology that uses computers to look at hundreds of genes in cancer cells. The results can help guide treatment decisions.

NGS tests look for genetic changes called somatic mutations:

• Somatic mutations are gene changes that happen to cells over time, after a person is born.
• These are different than inherited genetic mutations, such as BRCA1 and BRCA2.
• You cannot inherit somatic mutations from your parents or pass them to your children.
• In some cases, environmental factors can lead to somatic mutations. But these mutations often happen by chance.

A somatic mutation is one of many breast cancer biomarkers that can tell you and your doctor what might be causing the cancer to grow—and in some cases, what therapies might be able to treat it.

You may hear different names for tests that use NGS. These include:

• Somatic mutation tests
• Broad molecular profiling
• Comprehensive genomic profiling tests
• Genomic testing
• Biomarker testing
• Massively parallel sequencing

Right now, NGS is recommended only in breast cancer that is metastatic or cannot be removed by surgery. Tests that use NGS can confirm if the cancer has mutations in genes such as AKT1, ESR1, and PIK3CA. There are metastatic breast cancer treatments available that target these and other mutations found in NGS testing.

Below, we’ll walk you through all the genetic changes NGS can find that can be matched to available treatments. We’ll also explain when to ask about NGS testing, how it works, and what results may look like on a report.

Who gets NGS testing?

Doctors may recommend NGS tests for people with metastatic breast cancer or advanced breast cancer that cannot be removed with surgery.

Guidelines suggest using NGS tests only when it’s likely they could find a mutation that can be matched to a treatment.

NGS testing is generally not used in early-stage breast cancer, because early-stage treatment is determined using traditional biomarkers such as hormone receptors and HER2 receptors. There is not enough data to support changing this early-stage treatment approach with the use of NGS testing.

When can NGS testing be done?

NGS tests can be given:

• At the time of a first advanced or metastatic breast cancer diagnosis
• When metastatic breast cancer grows or spreads (progresses)
• If a treatment is no longer working as well

If cancer progresses, it can sometimes mean that genes in the cancer have mutated. NGS testing can confirm if there are new gene mutations that can be matched to a targeted therapy.

NGS tests may also be used in clinical trials if researchers are studying:

• A certain somatic gene mutation
• How a treatment works in cancers with different gene mutations

If you have been diagnosed with advanced or metastatic breast cancer, ask your healthcare team about NGS testing any time you’re considering a new treatment.

How does NGS testing work?

NGS tests can be performed on a blood sample or tumor tissue removed during a biopsy.

First, the blood or tissue sample is sent to a lab. In the lab, NGS tests can take DNA from the sample.

Then, the DNA is processed through a computer program that captures information from hundreds of genes. This program compares cancer cell DNA to healthy cell DNA to identify mutations in the cancer cells.

Test results can tell if the cancer has a specific gene mutation that might be a match for a treatment.

Types of tests that use NGS

Circulating tumor DNA, or ctDNA, is a blood test that often uses NGS. ctDNA tests are one type of liquid biopsy. ctDNA tests look at blood for cancer DNA that has broken away from a tumor.

There are many NGS tests available. Some large cancer centers use NGS tests they develop in their own labs. Doctors can also order commercially available tests, including these:

Tissue tests

• Foundation One CDx
• MI Tumor Seek Hybrid by Caris Life Sciences
• OmniSeq INSIGHT by Labcorp Oncology

Blood tests

• Guardant 360 CDx
• FoundationOne Liquid CDx
• Caris Assure

How NGS test results are reported

After lab professionals perform an NGS test, they will generate a report. The report is shared with you and your doctor.

Different companies and labs report NGS test results in different ways. Still, your report will likely include some or all of these:

• A list of gene mutations found in the cancer
• Information on treatments that can target specific gene mutations found in the test
• A list of clinical trials you might be eligible for based on the results

These reports are prepared for your healthcare team and may contain a lot of information you don’t understand or don’t know what to do with. That is OK. Your doctor can walk you through the findings and how they may affect your care.

If you are concerned about what the test may find, let your team know before the test. Ask them what information they are looking for and how that can inform your treatment options.

NGS test results and treatment decisions

Right now, NGS tests can find the following gene changes that can potentially be matched with a treatment:

• AKT1: Hormone receptor-positive metastatic breast cancer that has a gene mutation called AKT1 may qualify for treatment with capivasertib (Truqap).
• ESR1: If hormone receptor-positive metastatic breast cancer has an ESR1 mutation, elacestrant (Orserdu) may be a treatment option.
• NTRK: Some metastatic breast cancers test positive for a type of change called a gene fusion that includes the NTRK gene. There are two medicines that target NTRK gene fusion: larotrectinib (Vitrakvi) and entrectinib (Rozlytrek).
• PIK3CA: There are three treatments for hormone receptor-positive metastatic breast cancer that tests positive for a PIK3CA gene mutation: alpelisib (Piqray), capivasertib, and inavolisib (Itovebi).
• PTEN: Some hormone receptor-positive metastatic breast cancers that test positive for a PTEN alteration may be treated with capivasertib.
• RET: Metastatic breast cancers found to have a gene fusion that includes the RET gene may qualify for treatment with selpercatinib (Retevmo).

NGS tests can also look for two other genetic changes that can happen in metastatic breast cancer:

• TMB: Tumor mutational burden, or TMB, is a measure of how many DNA changes are in the cancer cells. Breast cancer with a high TMB may be treated with the immunotherapy pembrolizumab (Keytruda).
• MSI-H: Breast cancer that is microsatellite instability-high, or MSI-H, has many repeating DNA patterns. These cancers may be treated with immunotherapies such as pembrolizumab or dostarlimab (Jemperli).

To learn more about these gene changes and other characteristics that guide treatment, visit biomarker testing.

Paying for NGS tests

Tests that use NGS are more likely to be covered if the cancer and the test meet certain requirements. Medicare and Medicaid guidance for NGS tests say the cancer should be:

• Advanced, meaning it can’t be removed by surgery; or
• Metastatic, meaning it has traveled to other parts of the body

Talk with your healthcare team about coverage for NGS tests, including what an insurance company may ask for before approving the test. You can also ask about the possibility of joining a clinical trial. Some trials may provide NGS tests at no cost.

Visit our page on financial matters to learn more about paying for tests and treatment.