Genomic tests analyze a sample of a cancer tumor to see how active certain genes are. The activity level of those genes affects the behavior of the cancer, including how likely it is to grow and spread. The suite of genes that are analyzed are called biomarkers.
For breast cancer, the genomic tests are used mainly to analyze early-stage, hormone-receptor-positive, HER2-negative-breast cancer to predict of the risk of recurrence -- the cancer coming back -- usually within 5 to 10 years after diagnosis.
Researchers compared the ability of four genomic tests:
- Breast Cancer Index -- analyzes the activity of 7 genes
- Oncotype DX -- analyzes the activity of 21 genes
- Prosigna Breast Cancer Prognostic Gene Signature Assay -- analyzes the activity of 58 genes
- EndoPredict -- analyzes the activity of 12 genes
to predict distant recurrence -- the cancer coming back in a part of the body away from the breast -- for 0 to 10 years and 5 to 10 years after diagnosis.
The research was published online on Feb. 15, 2018 by JAMA Oncology. Read “Comparison of the Performance of 6 Prognostic Signatures for Estrogen Receptor-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.”
It’s important to know that the title of the article suggests six genomic tests were compared. In reality, the researchers compared the four genomic tests and also used immunohistochemistry (IHC) testing to determine HER2 and hormone receptor status and a clinical treatment score (node status, tumor size, cancer grade, the woman’s age, and hormonal therapy treatment information) to add to information provided by the genomic tests.
While the genomic tests are similar, there are some important differences between them:
- The Breast Cancer Index test is used to estimate the risk of node-negative, hormone-receptor-positive breast cancer coming back 5 to 10 years after diagnosis and to predict the benefit of an additional 5 years of hormonal therapy.
- The Oncotype DX test is used to estimate the risk of recurrence of early-stage, hormone-receptor-positive breast cancer, as well as how likely it is that a woman diagnosed with this type of cancer will benefit from chemotherapy after surgery.
- The Prosigna Breast Cancer Prognostic Gene Signature Assay (formerly called the PAM50 test) is used to estimate the risk of distant recurrence for postmenopausal women within 10 years of diagnosis of early-stage, hormone-receptor-positive disease with up to three positive lymph nodes after 5 years of hormonal therapy.
- The EndoPredict test is used to estimate the risk of distant recurrence of early-stage, hormone-receptor-positive, HER2-negative breast cancer that is either node-negative or has up to three positive lymph nodes.
To clearly understand the results of this study, it’s important to know the difference between prognostic biomarkers and predictive biomarkers.
A prognostic biomarker gives doctors and patients information about a likely cancer outcome -- disease recurrence or disease progression, for example -- independent of any treatment received. So, no matter which treatments are given, if any, prognostic biomarkers are giving an estimate of what the cancer is likely to do.
A biomarker is predictive if a treatment causes a different effect in patients that are biomarker-positive compared to patients that are biomarker-negative.
So, while all the genomic tests looked at in this study include prognostic biomarkers, only the Oncotype DX test can estimate how likely it is that a woman diagnosed with early-stage, hormone-receptor-positive, HER2-negative breast cancer will benefit from chemotherapy.
The study included information from 774 postmenopausal women diagnosed with early-stage, hormone-receptor-positive, HER2-negative breast cancer; 591 of the women had node-negative disease. The researchers looked at genomic tests results and then looked to see how many women had a recurrence.
For women diagnosed with hormone-receptor-positive, HER2-negative, node negative breast cancer, the study found that Prosigna Breast Cancer Prognostic Gene Signature Assay, the Breast Cancer Index test, and the EndoPredict test provided more prognostic information about distant recurrence 5 to 10 years after diagnosis than the Oncotype DX test. For women with 1 to 3 positive lymph nodes, all the tests provided limited prognostic information.
Other tests outperformed the Oncotype DX test in this study when it came to estimating breast cancer recurrence. Still, Oncotype DX is the only test recommended in major guidelines for predicting the benefit of chemotherapy in women diagnosed with early-stage breast cancer. The Breast Cancer Index test is used to predict the benefit of an additional 5 years of hormonal therapy after 5 years of tamoxifen in postmenopausal women diagnosed with early-stage breast cancer.
“The key difference is that predictive biomarker tests, such as the Oncotype DX test and Breast Cancer Index test, are associated with a difference in outcome based on a specific treatment,” said Brian Wojciechowski, M.D., Breastcancer.org medical adviser. “There are a million biomarkers that prognosticate a higher risk of X in the future. There are very few that have been shown to actually predict a different outcome based on treatment for those at high risk.”
So, the bottom line is that all the tests do a pretty good job of estimating the risk of late distant recurrence for early-stage, hormone-receptor-positive, HER2-negative breast cancer, but only the Oncotype DX test has strong research showing that it can predict how likely it is that a woman diagnosed with this type of breast cancer will benefit from chemotherapy after surgery.
For more information on genomic assays for breast cancer, visit the Breast Cancer Tests: Screening, Diagnosis, and Monitoring page.