Study Confirms Accuracy for Test to Guide Early Breast Cancer Treatment

Approximately 46 percent of patients with breast cancer at high risk for recurrence but low genomic risk according to the 70-gene breast cancer recurrence assay (MammaPrint) might not require adjuvant chemotherapy. These five-year data from the MINDACT trial were published in The New England Journal of Medicine.

The percentage of patients classified as low risk were shown to have prolonged survival regardless of receiving adjuvant chemotherapy, giving MammaPrint level 1A clinical evidence and confirming the clinical utility of MammaPrint. Initial results of the MINDACT trial were presented at the 2016 American Association for Cancer Research Annual Meeting, which showed that MammaPrint demonstrated a high level of accuracy at identifying a large subset of women with clinically high-risk early stage breast cancer for whom adjuvant chemotherapy was unlikely to produce benefit.

“When we developed MammaPrint, we knew we wanted to achieve the same level of evidence required for a typical pharmaceutical drug,” said study author Laura van’t Veer, M.D., chief research officer, Agendia, leader, Breast Oncology Program, and director, Applied Genomics at UCSF Helen Diller Family Comprehensive Cancer Center, in a statement. “That is why we are one of only a few diagnostic tests with FDA clearance and why we rigorously evaluated MammaPrint in the context of clinical-pathological factors in the randomized MINDACT trial. Now indeed, we have the only genomic assay with level 1A evidence to help physicians more accurately predict risk of distant metastasis in patients with early-stage breast cancer.”

In the phase 3 randomized, controlled study, 6,693 patients were evaluated with Mammaprint to help predict clinical outcome in women with early-stage disease. Patients were stratified into four subgroups: low clinical risk/low genomic risk (2,745 patients), low clinical risk/high genomic risk (592 patients), high clinical risk/low genomic risk (1,550 patients ) and high clinical risk/low genomic risk (1,806 patients).

Altogether, 88 percent of the patients enrolled had hormone receptor (HR)-positive tumors and 10 percent had biologically aggressive HER2-positive disease. After a median follow-up of five years, 3 percent of the study population died and 5.4 percent experienced either distant metastases or death.

Among the 1,550 patients (23.2 percent) with high clinical risk and low genomic risk, the five-year survival rate without distance metastasis was 94.7 percent for those who did not receive chemotherapy. In those who did receive chemotherapy, the survival difference was 1.5 percentage points, with the rate being lower without chemotherapy. Among patients in the intention-to-treat population who were at high clinical risk and low genomic risk at enrollment, those who underwent randomization on the basis of clinical risk and received chemotherapy had a five-year survival rate without distant metastasis of 95.9 percent. For those who underwent randomization based on genomic risk and did not receive chemotherapy had a rate of 94.4 percent. This was 1.5 percentage points lower than the rate among those who received chemotherapy.

Similar survival rates without distance metastases were observed in the estrogen-receptor—positive, HER2-negative subgroup, the authors noted, and either node-negative or node-positive disease.

Gabriel Hortobagyi, M.D., Professor and Chair Emeritus, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, chair of Agendia Inc Medical Advisory Board, said that the MINDACT trial design demonstrates the clinical utility of the assay.

“The reporting of these conclusive results of the trial will now give physicians increased confidence that in using MammaPrint, their treatment decisions will be based on the highest level of clinical evidence and will minimize the incidence of over- or under-treatment,” said Hortobagyi in a statement.

The MINDACT trial was opened in 2007 and originally included women with negative nodes, but was amended in 2009 to enroll women with one to three positive nodes. MINDACT enrolled patients 112 centers in nine European countries who had their risk of tumor recurrence following surgery assessed through use of MammaPrint, performed on frozen tumor tissue, and also via Adjuvant! Online.

“The quality of life and cost efficiency implications of helping physicians choose the appropriate management for women with breast cancer is the reason we do what we do every day,” said Mark Straley, chief executive officer, Agendia, in a statement. “We understand that ultimately, the decision to receive or forgo chemotherapy lies with each patient and physician who is properly informed about the potential side effects and benefits of such treatment. Nonetheless, MammaPrint could potentially change the standard of care and we look forward to its recommendation for inclusion in all early-stage breast cancer management guidelines. This will ensure that even more patients, physicians and healthcare systems are aware of the benefits of MammaPrint-based management decisions.”