Genomic Risk Assessment Aids Early-Stage Breast Cancer Chemotherapy Decisions

Use of a 70-gene assay could enable a reduction in adjuvant chemotherapy utilisation in a specific subset of early-stage breast cancer patients

medwireNews: Considering the results of the 70-gene signature test MammaPrint alongside those of a standard clinical evaluation could help certain women with early-stage breast cancer avoid adjuvant chemotherapy, show phase III trial results.

The MINDACT (Microarray in Node-negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study enrolled 6693 women with stage T1, T2 or resectable T3 breast cancer who were stratified into four groups based on their genomic and clinical risk, as assessed by MammaPrint and a modified version of the Adjuvant! Online tool, respectively.

Patients with concordant findings – that is, those categorised as high or low risk according to both genomic and clinicopathological results – were treated accordingly (chemotherapy and no chemotherapy, respectively). But women whose genomic and clinical risk assessments did not concur underwent random assignment to either the no chemotherapy or chemotherapy arm.

In the primary analysis cohort, comprising 644 patients with high clinical and low genomic risk who adhered to the no chemotherapy assignment, the 5-year distant metastasis-free survival rate was 94.7%, which was above the prespecified noninferiority cutoff of 92%.

Furthermore, among all 1550 women stratified as having high clinical and low genomic risk (ie, intention-to-treat population), the 5-year distant metastasis-free survival rates for the no chemotherapy and chemotherapy groups were 94.4% and 95.9%, respectively, equating to a nonsignificant difference of 1.5 percentage points.

Fatima Cardoso, from Champalimaud Clinical Center–Champalimaud Foundation in Lisbon, Portugal, and co-researchers estimate that approximately 46% of women considered high risk on the basis of their clinical evaluation could potentially forego chemotherapy.

They also found that rates of distant metastasis-free survival at 5 years were comparable for the no chemotherapy and chemotherapy arms among patients classified as low clinical and high genomic risk (95.0 vs 95.8%). “This finding does not show any advantage of directing therapy on the basis of genomic risk among patients at low clinical risk but high genomic risk, since these patients had no benefit from the use of adjuvant chemotherapy”, the investigators write in The New England Journal of Medicine.

The authors of a linked editorial say that the trial provides “evidence that the genomic test can reassign some classically high-risk patients with early-stage breast cancer to a lower-risk cohort in whom any plausible chemotherapy benefit would be modest.”

However, they point out that “a difference of 1.5 percentage points, if real, might mean more to one patient than to another. Thus, the stated difference does not precisely exclude a benefit that clinicians and patients might find meaningful.”

Nonetheless, Clifford Hudis and Maura Dickler, both from the Memorial Sloan Kettering Cancer Center in New York, USA, believe that “these results could allow some doctors and patients to choose to avoid chemotherapy if they have carefully considered their own tolerance for toxicity, risk, and uncertainty.”


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 Engl J Med 2016; 375: 717–729. doi:10.1056/NEJMoa1602253

Hudis CA, Dickler M. Increasing precision in adjuvant therapy for breast cancer. N Engl J Med 2016; 375: 790–791. doi: 10.1056/NEJMe1607947

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