Experimental Genomic Test May Estimate Risk of Recurrence for Some Women

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A genomic test (also called a genomic assay) analyzes the activity of a group of genes linked to the risk of a particular disease. The tests are done on blood or tissue samples. For example, a genomic test may help figure out if a woman diagnosed with early-stage, hormone-receptor-positive breast cancer has a high, medium, or low risk of recurrence (the cancer coming back), as well as if she’s likely to benefit from chemotherapy to reduce that risk.

A study suggests that an experimental genomic test called PAM50 done on early-stage, hormone-receptor-positive breast cancer that’s been treated with hormonal therapy offers more information on a woman’s risk of recurrence than the Oncotype DX genomic test and the IHC4 test. The PAM50 test may estimate the risk of distant recurrence (the cancer coming back in a part of the body away from the breast) better than both of the other tests for some women.

The study was published online on July 1, 2013 by the Journal of Clinical Oncology. Read the abstract of “Comparison of PAM50 Risk of Recurrence Score With Oncotype DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy.”

The PAM50 test looks at the activity levels of 58 genes in early-stage, hormone-receptor-positive breast cancer. Based on these activity levels, PAM50 test results are reported as a risk of recurrence score that classifies women as having either high or low risk of breast cancer coming back somewhere in the body away from the breast more than 5 years after diagnosis.

The Oncotype DX test analyzes the activity levels of 21 genes in early-stage, hormone-receptor-positive breast cancer. Based on the activity levels, Oncotype DX test results are reported as a recurrence score – a number between 0 and 100:

  • a score lower than 18 means the cancer has a low risk of recurrence
  • a score between 18 and 31 means the cancer has an intermediate risk of recurrence
  • a score greater than 31 means the cancer has a high risk of recurrence

The Oncotype DX test also can be used to estimate the risk of recurrence of DCIS. The Oncotype DX test can help predict how a breast cancer will respond to chemotherapy. The PAM50 test doesn't.

The IHC4 test uses a special staining process to measure four measure four markers in cancer cells:

  • HER2 receptors
  • hormone receptors (both estrogen and progesterone)
  • Ki-67 levels

Ki-67 is a protein in cells that increases as they prepare to divide into new cells. The more cancer cells that are positive for Ki-67, the more quickly they’re dividing and forming new cells.

The IHC4 test results are reported as scores for the four markers. From that, doctors can estimate the risk of recurrence. Still, not all labs use the same method for analyzing the results of the IHC4 tests. The labs also don’t have to report the results in exactly the same way. Many doctors believe that IHC4 tests and results need to be standardized before the test is widely used.

In this study, the researchers wanted to see if the PAM50 test offered doctors more information on the outcome of early-stage, node-negative, hormone-receptor-positive breast cancer that had been treated with 5 years of Arimidex (chemical name: anastrozole) or tamoxifen than the Oncotype DX test or the IHC4 test. They also wanted to compare the accuracy of the PAM50 risk of recurrence score to the Oncotype DX recurrence score and the IHC4 score.

The large ATAC (Arimidex and Tamoxifen Alone or in Combination) trial compared Arimidex to tamoxifen in 6,241 postmenopausal women diagnosed with early-stage, node-negative, hormone-receptor-positive breast cancer. The researchers for this study analyzed about 1,000 tumor samples from women in the ATAC trial who had been treated with only Arimidex or only tamoxifen for 5 years:

  • 1,007 tumor samples were analyzed with the PAM50 test and the Oncotype DX test
  • 940 tumor samples were analyzed with the IHC4 test in addition to the PAM50 test and the Oncotype DX test

The researchers also looked at how much time passed before any distant recurrence happened.

After about 10 years of follow-up, the researchers used statistical analysis to compare the test scores and the time to distant recurrence. Overall, the PAM50 risk of recurrence score was more accurate at estimating the risk of distant recurrence 5 years after diagnosis than either the Oncotype DX recurrence score or the IHC4 score. It also was more accurate in classifying cancers as having intermediate and high risk of recurrence.

Knowing whether a woman has a high or low risk of breast cancer coming back in a part of the body away from the breast more than 5 years after diagnosis can help doctors decide how long hormonal therapy medicine should be taken. Research has shown that taking tamoxifen for 10 years instead of 5 years can better lower the risk of recurrence and improve overall survival for some women. If doctors knew that a woman had a low risk of distant recurrence, they could spare her the extra 5 years of hormonal therapy treatment. At the same time, women at high risk would benefit from the extra 5 years of treatment.

While the results of this study are promising, the PAM50 test, made by NanoString, isn’t yet available in the United States or approved by the U.S. Food and Drug Administration. The test has received the CE mark, which means it can be sold in European Union countries, as well as Iceland, Liechtenstein, and Norway. It also is important to know that most doctors will have more experience with the Oncotype DX test than the PAM50 test.

When making treatment decisions, you and your doctor will consider a number of factors, including:

  • your age
  • your menopausal status
  • the size of the cancer
  • hormone-receptor protein levels
  • cancer grade
  • your Oncotype DX score, if you've had that test

Armed with the best information possible, you and your doctor can decide on a treatment plan that makes the most sense for your unique situation.

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