Early-stage breast cancer: When is biomarker testing helpful?

In order to be able to give a woman advice about whether or not to have chemotherapy, doctors look at certain clinical criteria. These provide information about the characteristics of the tumor and the risk of it coming back. They are determined using a tissue sample that is taken during the breast cancer surgery. Other factors that doctors take into account include the woman’s age, whether she has already reached menopause, and whether she has other medical problems.

After considering all of this information, doctors give a recommendation about whether or not to have chemotherapy.

It is particularly hard for doctors to make a recommendation about chemotherapy for early-stage breast cancer if the following criteria coincide:

• the tumor has receptors for hormones such as estrogen and progesterone – in other words, it is hormone-receptor-positive,
• the tumor does NOT have a lot of receptors for certain growth factors – in other words, it is HER2/neu-negative, and
• the tumor hasn’t spread to any lymph nodes, or has only spread to three lymph nodes or less.

Can biomarker testing help in this situation?

Biomarker testing involves doing tests that determine the characteristics of the tumor that aren't covered by the clinical criteria. These are mainly particular changes (mutations) in the genes inside the tumor cells. Many biomarker tests are gene expression profiling tests. They find out whether various genes in the cancer cells are especially active.

To do biomarker testing, a sample of the tumor tissue is needed. The sample is usually taken during the breast cancer operation.

The biomarker test results help doctors to decide whether or not to recommend chemotherapy.

There are various biomarker tests. But only one of them – known as the Oncotype DX test – has been studied in research that has produced reliable results.

The Oncotype DX test is a gene expression profiling test that measures the activity of 21 genes. The test gives a score between 0 and 100. This score helps doctors to estimate the risk of recurrence and the likelihood of chemotherapy helping. Once the score has been determined, the woman talks to her doctor about the score and how it affects the decision about whether or not to have chemotherapy.

The research results described below apply to the above-mentioned group of women with early-stage breast cancer – but only those whose cancer hasn’t spread to any lymph nodes. There is no good research on the suitability of the Oncotype DX test for the women whose cancer has spread to lymph nodes. The research in this area is still ongoing.

The research on the Oncotype DX test shows that it can help women to decide whether or not to have chemotherapy. The test can identify two groups of women:

• 1st group: These women will not benefit from chemotherapy. They can avoid this treatment and the associated side effects. Doing so won't have any disadvantages for them.
• 2nd group: These women can benefit from chemotherapy.

The tables below show in more detail what the different Oncotype DX scores can mean for different groups of women.

The Oncotype DX test isn’t the only biomarker test for women with early-stage breast cancer. Other available tests include Endopredict, MammaPrint und Prosigna. There’s not yet enough research on them to be able to say whether they can reliably help to predict whether women are likely to benefit from chemotherapy. But studies are currently being done in this area.

In 2018, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) last looked into whether biomarker testing can help women decide whether or not to have chemotherapy. They focused on women who had hormone-receptor-positive and HER2/neu-negative early-stage breast cancer that had spread to three lymph nodes or less. If the breast cancer has these characteristics, it is particularly difficult for doctors to predict whether chemotherapy is likely to help.

The researchers at IQWiG found only one good-quality study in this area, and the study looked at only one specific test: the Oncotype DX test. This study, known as the “TAILORx study,” included only women whose breast cancer hadn't spread to any lymph nodes.

The study led to the conclusions described above. But a lot of research is currently being done on biomarker testing, so we should know more in the future.

The aim of this study was to find out whether the Oncotype DX test can determine which women don’t need to have chemotherapy.

The study only included women who had early-stage breast cancer,

• whose tumor was hormone-receptor-positive and
• HER2/neu-negative and
• hadn't spread to any lymph nodes.

All of the women in the study received hormonal therapy. They were assigned to one of three groups based on their Oncotype DX score:

• Score from 0 to 10: The women didn’t have chemotherapy.
• Score from 11 to 25: The women were randomly assigned to one of two groups. This makes it possible to directly compare the groups of women and assess the benefit of chemotherapy.
  • One group received chemotherapy.
  • The other group did not have chemotherapy.
• Score from 26 to 100: All of the women received chemotherapy.

Different Oncotype DX scores mean different things for different women, depending on factors like their age and whether they had already entered the menopause when they developed breast cancer. Overall, the study found the following:

1. Women under the age of 50: If the Oncotype DX score is between 0 and 10, there are good reasons not to have chemotherapy. If the score is higher, chemotherapy can have advantages.
2. Women over the age of 50: If the Oncotype DX score is between 0 and 25, there are good reasons not to have chemotherapy. If the score is higher, chemotherapy can have advantages.

The following tables show what different Oncotype DX scores mean. There is one table for women under 50 and one table for women over 50.