Nearly half of early-stage breast cancer patients classified as high clinical risk may not require chemotherapy, according to the results of a Phase 3 clinical trial conducted in several cancer centers in Europe.
The study, “70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer,” published in The New England Journal of Medicine, shows that patients associated with a low risk of disease recurrence — according to the results of a genetic test called MammaPrint — had very similar prognoses whether they received chemotherapy or not.
“For the first time, a prospective, randomized trial shows that the active biology of breast cancer in an individual, as assessed by the MammaPrint test, can assist in making a well-informed choice to undergo chemotherapy treatment or not,” said co-first author Laura van ’t Veer, PhD, an inventor of MammaPrint and director of Applied Genomics at the University of California at San Francisco Helen Diller Family Comprehensive Cancer Center.
Women with early stage breast cancer are commonly treated with either adjuvant chemotherapy, endocrine therapy, HER2 inhibitors, or combinations of these drugs when appropriate. Treatment decisions are currently based on conventional measures, such as tumor size, presence of hormone receptors, and metastasis to lymph nodes, as well as patient characteristics, such as age or menopausal status.
However, the individual biologic characteristics of the tumor are not taken into account and, as a result, many patients with breast cancer are overtreated and exposed to unnecessary risks of toxic effects from adjuvant therapy.
Today, several genomic tests have been developed to improve predictions of clinical outcomes and to determine whether the administration of chemotherapy is beneficial. One of these tests, the MammaPrint, assesses the expression of 70 individual genes to categorize tumors into groups of poor or good prognosis, based on the risk of tumor reappearance.
This MINDACT Phase 3 clinical trial, which was conducted by van ’t Veer; Dr. Fatima Cardoso, MD, director of the breast unit at the Champalimaud Clinical Center in Lisbon, Portugal; and Jan Bogaerts, PhD, of the European Organization for Research and Treatment of Cancer Headquarters, used MammaPrint in surgically removed tumors from 6,693 women to determine their genetic risk.
The research team revealed that approximately 23 percent of women who were considered candidates for chemotherapy based on their high clinical risk had low-risk tumors, according to MammaPrint results. To determine the benefits of chemotherapy in such patients, the researchers randomly assigned them into two groups: one group received chemotherapy and the other did not.
Results showed that the five-year survival rate of patients who did not receive chemotherapy was 94.7 percent, only 1.5 percent lower than the group of patients who received chemotherapy. Patients who did not receive chemotherapy also did not develop distant metastasis.
For the most common type of breast cancer, hormone receptor positive (HR+)/HER2-/lymph node negative (LNO) disease, three-quarters of patients had low genetic risk as assessed by MammaPrint. The five-year survival rate for patients with this type of breast cancer who did not receive chemotherapy was nearly 98 percent.
It is noteworthy that 46 percent of women with high clinical risk were found the have low genetic risk, suggesting that nearly half of patients who were previously indicated for chemotherapy treatment may not need chemotherapy.
“The MINDACT trial results are of great importance for early stage breast cancer patients,” van ’t Veer said.
In the future, MammaPrint genetic testing in breast cancer may help clinicians decide which patients are more likely to benefit from chemotherapy, reducing the number of patients exposed to the unnecessary toxic effects of such therapies.