Biomarker Tests for Early-Stage, Hormone Receptor-Positive Breast Cancers Show Promise, but More Research is Needed

Biomarker tests, often called genomic tests, were featured in two presentations at the ASCO Annual Meeting Monday morning. Biomarker tests look at specific features in tumor DNA to see how they will react to certain treatments. In breast cancer, biomarker tests are sometimes used to determine whether a person is eligible to get a certain type of treatment.

Both presentations showed positive results for new applications of existing tests under study; researchers hope these new ways of applying the tests will help direct treatments to people who need them, and save people who won’t benefit the time and financial costs of a treatment they don’t need. But both studies need more data before the new ways of using each test are is seen in doctors’ offices.

Biomarker Testing to Predict Extended Hormonal Therapy Effect

In the past, the phase III aTTom trial looked at whether taking 10 years of the hormonal therapy tamoxifen offered more protection from recurrence than taking 5 years of the medicine. The trial found that it did.

Today’s researchers want to see if the biomarker test Breast Cancer Index can predict in which specific people taking 10 years of tamoxifen offers more protection. They are looking into the use of the test through the Trans-aTTom study, using tumor samples from the participants in the aTTom study. The researchers tested tissue from participants’ primary tumor and compared the Breast Cancer Index results to see if taking tamoxifen longer benefitted them.

The Trans-aTTom study showed that taking tamoxifen for 10 years had

• no benefit for people with a Breast Cancer Index (H/I)-Low score, which means people with a low BCI score don’t gain from taking tamoxifen for 10 years instead of 5 years
• a 10.2 percent risk reduction for people with a Breast Cancer Index (H/I)-High score, which means people with a high BCI score do gain from taking tamoxifen for 10 years instead of 5 years

These results are good news for the biomarker test, because they provide additional support for its claims to be able to guide treatment. It also means the test may be helpful for people with hormone receptor-positive breast cancer who have to make the decision to continue hormonal therapy or not. But this use of the test is not ready to go into practice.

Monday’s results are only part of what will be the final analysis for Trans-aTTom. The study is looking at people with cancer in the lymph nodes and those without, and while the trial enrolled enough people with breast cancer in the lymph nodes to reach conclusions for that group, it has not yet recruited enough people with no cancer in the lymph nodes.

Vered Stearns, MD, from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, said in the discussion portion of the presentation that any changes to care based on these study results should wait for the full results that include people with node-negative breast cancer.

Still, the findings do show the possibility for doctors to limit extended hormonal therapy to only the people it is most likely to help. This is of special interest after a poster presented yesterday that explored the quality of life of people during and after breast cancer treatment. That poster reminded doctors and researchers that hormonal therapies have an effect on quality of life, and that they should look for ways to give it less without compromising safety.

Using Clinical Risk and Test Scores Together

The TAILORx trial made news last year when it suggested that many women with hormone receptor-breast cancer that has not traveled to the lymph nodes can skip chemotherapy treatment based on their results from the Oncotype DX biomarker test. The study findings provided answers for many women who were considered at intermediate risk of recurrence, and for whom there was no clear answer on whether chemotherapy was useful and worth the side effects.

This year brought a planned secondary analysis of the TAILORx study, looking to refine results by looking at clinical risk factors such as tumor size and grade.

In the TAILORx trial 9,427 women were given the Oncotype DX text and put into treatment groups based on their Recurrence Score:

• Those with a Recurrence Score below 11 did not get chemotherapy.
• Those who got a Recurrence Score above 25 did get chemotherapy.
• Those given a score from 11 to 25 were randomized to get chemotherapy or not.

In this analysis, the researchers looked at each of the above groups, and whether the people in them had high or low clinical risk based on their tumor size and grade. They found that clinical risk added information to help predict disease-free survival, the time from the start of treatment until the cancer returns.

Within these Recurrence Score groups (11 and below, 11 to 25, and 25 and above), women who were found to have a high clinical risk were more likely to have breast cancer return than women who were found to have a low clinical risk. Women with high clinical risk were also more likely to have breast cancer return to parts of the body away from the breast.

Despite this, the study also found that clinical risk could not predict if chemotherapy should be added to a person’s treatment plan. While clinical risk can identify women who may be more likely to have breast cancer return, it cannot say if giving them more treatment will lessen that risk or not. Still, the finding that clinical risk fits into the discussion of Oncotype DX results can help doctors and patients have better discussions about treatment and bring more information to decisions.