Breast cancer patients who are identified as low-risk by a 70-gene test may be able to avoid chemotherapy, even if they are considered to be high-risk by traditional criteria, according to new results from an ongoing, large study called MINDACT (Microarray In Node-negative Disease may Avoid ChemoTherapy). The results provide new evidence on this genetic test and were recently published in the New England Journal of Medicine.
The test, called MammaPrint, analyzes 70 genes in breast cancer tissue and was originally approved by the Food and Drug Administration in 2007. The MINDACT trial is comparing the MammaPrint test with certain traditional (clinical and pathologic) criteria in deciding whether patients should undergo chemotherapy treatment. Nearly 6,700 women with early stage breast cancer across 9 European countries have participated in the study.
The results could be significant for the nearly quarter of a million American women who are affected by breast cancer each year. Breast cancer is the second most frequently diagnosed cancer in women in the U.S. and is the second leading cause of cancer death, according to the American Cancer Society.
Treatment of breast cancer typically includes a combination of surgery, radiation, chemotherapy, hormone therapy, and/or targeted therapy. Ideally, treatments are tailored for the patient and the specific cancer type. Some patients who are considered to be low-risk of relapse and have a good prognosis may not require chemotherapy and can avoid the associated side effects. However, it can be difficult to determine who can safely opt out of chemotherapy.
Healthcare practitioners have traditionally used several parameters to try to identify which patients might avoid chemotherapy. Some factors include the patient's age and health, tumor size, hormone status, cancer grade (how normal or abnormal the tumor's cells are) and stage of the cancer (whether it has remained localized, is present in lymph nodes close to the tumor, spread to nearby tissues, or spread to other organs).
MammaPrint provides genetic information in addition to these criteria. It analyzes a panel of 70 genes in the breast cancer tissue and calculates a score. Based on that score, a patient may be categorized as high-risk or low-risk.
For the MINDACT study, researchers used both clinical criteria and genetic information from the test to classify women into different categories of risk. One group was classified as high-risk by clinical criteria but low-risk by MammaPrint. A primary goal of the study was to determine whether these women could forego adjuvant chemotherapy. Women who were classified into this group were randomly assigned to receive chemotherapy or no chemotherapy and were followed for five years.
According to the researchers, the difference in the results between the women who received chemotherapy and those who did not was not significant. At five years, patients who had chemotherapy had somewhat higher survival rates (1.5%) with cancers that did not spread to other areas of the body compared to those who had not received chemotherapy. (The five-year survival rate without distant metastasis was 1.5% higher in the group that received chemotherapy compared to those who did not.) Based on the size of the study, this was within the range of difference expected by chance alone and thus observation without chemotherapy was not felt to be inferior to use of chemotherapy in preventing spread of the cancer.
"Not all patients who currently receive adjuvant chemotherapy need the treatment, and they endure significant adverse side effects without gaining clinical benefits," said lead investigator Martine Piccart, MD, PhD, head of the Department of Medicine at the Jules Bordet Institute in Brussels, in an article in Medscape Medical News. "These new results show that use of this genomic assay helps to identify those patients that can skip chemotherapy, even if they are assessed clinically as being high risk."
However, an editorial in the same NEJM issue noted that the difference in results between those who had chemotherapy and those who did not may be more significant to some patients than others. The authors of the editorial, Clifford A. Hudis, MD, CEO of the American Society of Clinical Oncology, and Maura Dickler, MD, of the Memorial Sloan Kettering Cancer Center, said that patients who hope to avoid chemotherapy may choose to undergo genetic testing but that "[w]hat doctors and their patients do with the results of such testing will be highly individualized — and will inevitably be finessed by findings from future studies."
The MINDACT study researchers likewise concluded, "Ultimately, the decision to receive or forgo chemotherapy (or any other treatment) lies with each patient who is properly informed about the potential side effects and the potential benefits of such treatment. For the same risk-benefit scenario, different patients may make different decisions."