MINDACT Trial: 70-Gene Signature Spares 46% of High-Clinical-Risk Breast Cancer Patients From Chemotherapy
In this landmark phase 3 trial of 6,693 women with early-stage breast cancer, those classified as high clinical risk but low genomic risk by the 70-gene MammaPrint signature had a 94.7% five-year distant metastasis-free survival rate without chemotherapy · only 1.5 percentage points lower than with chemotherapy. The findings demonstrate that nearly half of women who would receive chemotherapy based on clinical criteria alone can safely forgo it when guided by genomic testing. This trial established the clinical utility of gene expression-based companion diagnostics in breast cancer treatment decisions.
The original study
70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.
- Authors
- Cardoso F, van't Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S, et al.
- Journal
- The New England journal of medicine
- Type
- Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- PMID
- 27557300
Original abstract
BACKGROUND: The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. METHODS: In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher. RESULTS: A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease. CONCLUSIONS: Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.).