Approximately 46% of patients with breast cancer at high risk for recurrence but low genomic risk with the 70-gene breast cancer recurrence assay (MammaPrint) might not require adjuvant chemotherapy, according to prospective 5-year results of the MINDACT trial published in
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 AACR 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, MD, 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 III randomized, controlled study, 6693 patients were evaluated with Mammaprint to help predict clinical outcome in women with early-stage disease. Patients were stratified into 4 subgroups: low clinical risk/low genomic risk (2745), low clinical risk/high genomic risk (592), high clinical risk/low genomic risk (1550), and high clinical risk/low genomic risk (1806).
Altogether, 88% of the patients enrolled had hormone receptor (HR)-positive tumors and 10% had biologically aggressive HER2-positive disease. After a median follow-up of 5 years, 3% of the study population died and 5.4% experienced either distant metastases or death.
In the 1550 patients (23.2%) with high clinical risk and low genomic risk, the 5-year survival rate without distance metastasis was 94.7% for those who did not receive chemotherapy (95% CI, 92.5-96.2). 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 5-year survival rate without distant metastasis of 95.9% (95% CI, 94.0-97.2). For those who underwent randomization based on genomic risk and did not receive chemotherapy had a rate of 94.4% (95% CI, 92.3-95.9). This was 1.5 percentage points lower than the rate among those who received chemotherapy (HR, 0.78; 95% CI, 0.50 to 1.21; P
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, MD, FACP, FASCO 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, a 2015 Giant of Cancer Care in Breast Cancer, 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 1 to 3 positive nodes. MINDACT enrolled patients 112 centers in 9 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.”
- 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 Eng J Med. 2016; 375:717-729.
- Piccart M, Rutgers E, van’t Veer L, et al. Primary analysis of the EORTC 10041/ BIG 3-04 MINDACT study: a prospective, randomized study evaluating the clinical utility of the 70-gene signature (MammaPrint) combined with common clinical-pathological criteria for selection of patients for adjuvant chemotherapy in breast cancer with 0 to 3 positive nodes. Presented at: AACR Annual Meeting 2016, New Orleans; April 16-20, 2016. Abstract CT-039.