MammaPrint test results may help decide treatment

MammaPrint, a test that looks at 70 genes in a breast cancer tumor, may be used to help some women with early-stage disease avoid chemotherapy, a phase III study released in the New England Journal of Medicine found.

Background

Treatment decisions have long been made based on clinical features, characteristics of the disease like tumor size and if the cancer has spread to the lymph nodes. Characteristics of the person being treated, such as age, are also considered. Recently, genomic tests like Oncotype DX and MammaPrint, which look at the genes in a tumor, have entered this discussion. These tests can tell how likely it is the cancer will come back within 5 and 10 years of diagnosis and whether chemotherapy can lower that risk.

Doctors use information about the tumor, the person and the genes in a tumor to speak with people about their risk of recurrence and whether chemotherapy will lower their risk.  Sometimes the tumor’s clinical features and the genomic test results do not match.  For example, a person may have a large tumor or lymph node-positive disease, both of which are associated with a high risk of cancer returning, but get genomic test results that show a low risk of cancer returning. It is not clear whether people with mismatched test results should be treated as high risk and receive chemotherapy, or if they should be treated as low-risk and receive no chemotherapy.

This study was designed to see if MammaPrint results could be used to help guide treatment decisions when the tumor’s clinical characteristics and genomic test results do not match.

Design

This study included 6,693 women. The study accepted women ages 18 to 70 with early-stage breast cancer, though most of them were between ages 35 and 70. Women with positive lymph nodes as well as negative lymph nodes were enrolled.

Most of the women in this study had ER-positive, HER2-negative tumors smaller than 5 centimeters, with cancer found in three or fewer lymph nodes. Researchers reported results after following the participants for 5 years.

Women were determined to have a high risk or a low risk of cancer returning based on:

• Clinical features using Adjuvant! Online, a computer program that calculates risk based on features like age, tumor size, and whether the lymph nodes are involved with cancer; and
• Risk results of the MammaPrint test

The focus of the study was women whose risk according to clinical features and MammaPrint did not match – they had a high risk in one and low risk in the other. These women were randomly assigned to get chemotherapy or not.

The researchers were most interested in comparing:

• Women who tested as high risk in clinical tests and low risk by MammaPrint and who were treated with chemotherapy
• Women who tested as high risk in clinical tests and low risk by MammaPrint who did not get chemotherapy

Women who enrolled and had scores that matched were advised to get the treatment based on those risks. If a participant was considered low risk by both tests they did not receive chemotherapy, and if a participant was high risk by both tests they did receive chemotherapy.

Results

There were 1,550 women who had a high risk according to clinical tests, but a low risk according to MammaPrint. The study found:

• In the group that received chemotherapy,   95.9% were alive and without a distant recurrence 5 years later
• In the group that did not get chemotherapy , 94.7% were alive and without a distant recurrence 5 years later

This means that people in both groups did well regardless of whether they received chemotherapy.  The risk of cancer spreading beyond the breast differed only 1.5 percent between the two groups, which is not meaningfully different.  The study finds that, for people who have high-risk clinical features but low-risk MammaPrint results, treatment decisions can be made based on the MammaPrint results. This allows many women to avoid the side effects associated with chemotherapy.

This analysis reported results from the first 5 years of follow-up.  The researchers are continuing to collect data to see if results are the same 10 years after a diagnosis.

What this means for you

You may be worried about the prospect of chemotherapy but see it as important for getting rid of cancer. Many factors are used to decide whether chemotherapy is best for you. MammaPrint adds to your doctor’s ability to predict your risk of breast cancer returning, but its results should be considered along with clinical and personal factors like age, lymph node status and tumor size.

Oncotype DX is already used in helping people choose treatment, but is limited to hormone-positive, HER2-negative breast cancers. MammaPrint can help provide information on breast cancers of any receptor status, meaning more people will be able to get a genomic test. The researchers say these results could mean 46 percent of women considered to have a high risk based on current clinical tests may have the option to not get chemotherapy.

The final decision is always with you, the person getting treatment. Your doctor may start using MammaPrint more before recommending treatment, and if he or she doesn’t, it is OK to ask why or to request you have the test. Speak with your doctors about what your results mean and what is important to you in treatment.

Cardoso, F; van’t Veer, LJ; Bogaerts, J; et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med 375:717-729, Aug. 25, 2016; doi: 10.1056/NEJMoa1602253