For nearly 20 years, Agendia’s tests have been evaluated through extensive clinical trials and research collaborations resulting in hundreds of publications that demonstrate the clinical utility of MammaPrint and BluePrint.
MammaPrint, the 70-gene risk of recurrence assay for patients with early stage breast cancer, is the first FDA-cleared and CE-marked test of its kind backed by peer-reviewed, prospective outcome data and included in major treatment guidelines. It is supported by the highest level of clinical evidence (level 1A) from MINDACT1, a landmark independent trial published in the New England Journal of Medicine in 2016. Additional long-term follow up data was presented at ASCO 2020, further validating the findings reported in 2016.
MINDACT (Microarray In Node-negative and 1-3 node-positive Disease may Avoid ChemoTherapy) was a phase III, prospective, randomized clinical study supported by the European Organization for Research and Treatment of Cancer (EORTC-10041/BIG3-04). The trial was designed primarily to determine whether the MammaPrint test could be used to safely de-escalate patients with early stage breast cancer from chemotherapy treatment without compromising their outcomes.
Study participants were categorized as low or high risk for breast cancer recurrence in two ways: first, using Adjuvant! Online, a tool which calculated recurrence risk based on common clinicopathological factors; and second, through analysis of tumor tissue using MammaPrint.
Patients characterized as low risk with both clinical and genomic assessments were spared chemotherapy, while patients characterized as clinical and genomic high risk were advised to undergo chemotherapy. Those with discordant results were randomized to use either clinical or genomic (MammaPrint) risk evaluation to determine the need for chemotherapy.
MINDACT Long-Term Follow Up Data2 Presented at ASCO 2020
Important data with median follow-up approaching 9 years were presented at ASCO 2020 confirming and expanding upon the 2016 MammaPrint findings published in the New England Journal of Medicine. These long-term data confirm MINDACT as a positive de-escalation trial for patients with early stage breast cancer:
- With follow up data available for 90% of patients, the 5-year DMFS for clinical high risk, MammaPrint Low Risk patients who were not treated with chemotherapy was 95.1%
- The difference in 5-year DMFS for clinical high risk patients treated with and without chemotherapy narrowed from 1.5%, as reported in 20161, to 0.9% confirming the appropriateness of treatment de-escalation in this population
- For clinically high-risk women over 50 with a MammaPrint Low Risk result, there was no difference in DMFS amongst those treated with or without chemotherapy (8-yr DMFS: 90.2% vs. 90.0%)
- These data confirm that women over 50 who are MammaPrint Low Risk may safely forgo chemotherapy following surgery, despite having clinically high risk features.
- Consistent with previously reported data for younger women (<50 years old)3, a 5% benefit from chemotherapy was seen at 8 years in patients with high clinical risk disease and a genomic Low Risk result, suggesting secondary ovarian suppression from chemotherapy as a possible explanation
- This benefit, observed only in younger patients, and its timing, is consistent with observations from the SOFT and TEXT trials4,5
- Confirming the initial results from 2016, chemotherapy did not appear to benefit clinical high risk/MammaPrint Low Risk patients with positive lymph nodes, even with longer-term follow-up.
How does MINDACT impact patient care?
- MammaPrint enables confident treatment planning for all early stage breast cancer patients
- MammaPrint reduces chemotherapy utilization by 46%, sparing patients from the unnecessary burden of treatment side effects
- For women over 50, MINDACT provided long-term follow-up data confirming those with a MammaPrint Low Risk result may safely avoid chemotherapy, regardless of clinical risk
- For women 50 and younger, MammaPrint results can be used as part of shared decision making regarding ovarian suppression or chemotherapy
In 2015, PROMIS2 (Prospective Study of MammaPrint in Breast Cancer Patients with an Intermediate Recurrence Score) evaluated 840 patients with early-stage breast cancer who had received an “intermediate” recurrence result from the Oncotype DX genomic test. The aim was to assess the change in physician treatment decisions after receiving a MammaPrint result.
When analyzing the subgroup of 368 patients for whom the original treatment recommendation (based on the Oncotype DX intermediate result) conflicted with that indicated by MammaPrint, 76% of patients had their treatment plan changed, with chemotherapy either added or removed.
The study’s authors concluded that MammaPrint provides clinically actionable information on patients who were classified as intermediate risk by the Oncotype DX (21-gene signature) test, and that physicians may consider ordering MammaPrint to help with treatment decisions for these patients.
In 79% of cases, physicians reported greater confidence in their treatment recommendation based on MammaPrint results.
In a study3 published in 2017, MammaPrint was used to analyze 652 patient samples with 20-year follow-up data from the prospective,† randomized‡ Stockholm Tamoxifen Trial.
It demonstrated that a new MammaPrint threshold could identify a subgroup of patients with exceedingly low risk of cancer recurrence 20 years after diagnosis (Late Recurrence (20yr) Low Risk).
These patients, most of whom received only two years of treatment with tamoxifen, had an observed 20-year breast cancer specific survival of 97%. Patients with a Late Recurrence (20yr) Low Risk result who did not receive any treatment post-surgery (neither chemotherapy nor hormone therapy) had a 94% breast cancer specific survival rate.
This information can be helpful to physicians in deciding whether to recommend extended, standard, or limited hormone therapy for certain patients. It gives both physicians and their patients more options for better management of the disease.
Where to next?
*The time to appearance of distant metastasis. A distant metastasis refers to cancer that has spread from the original tumor to distant organs.
†Prospective refers to when patients are recruited to a clinical study and followed forward in time.
‡Randomization is a procedure to allocate clinical study participants into different groups. By using chance to allocate participants, the groups are likely to be similar and allow the effects of the treatments to be compared more fairly.
1 Cardoso, F., et al. N Engl J Med 2016;375:717-29.
2 Cardoso, F., et al. ASCO 2020. J Clin Oncol 38: 2020 (suppl; abstr 506)
3 Sparano, JA., et al. N Engl J Med 2019; 380:2395-2405
4 Francis PA., et al. N Engl J Med 379:122-137, 2018
5 Pagani, O., et al. J Clin Oncol. 2020 Apr 20;38(12):1293-1303