Top Line: Does age influence the MammoPrint 70-gene signature’s clinical utility for predicting chemotherapy benefit?
The Study: Today we’re bringing the MINDACT trial back to the forefront with long term updates. As a reminder this trial stratified pT1-3N0-1 patients by both clinical and genomic risk. Clinical risk was dichotomized based on input of readily available clinical data into the Adjuvant! Online calculator with a cut-off of >88% and >92% for estimated 10-year breast cancer specific survival for ER+ and ER- tumors, respectively. Women who were both clinically and genomically high risk got adjuvant chemo, those who were low-low did not, and those with high clinical risk but low genomic risk (n=1497) were randomized to +/- chemo. In the original publication, the primary endpoint of mets-free survival at 5 years was non-inferior when chemo was omitted in women with high risk clinical features but low genomic risk. Here, long-term outcomes show that the 70-gene signature remains a strong predictor of clinical outcomes with an 8-year mets-free survival of 92% with chemo and 89.4% without—although the absolute difference grew from 1.5% to 2.6% over that time. Exploratory analyses were also performed in the subset of women with hormone receptor(+), HER2(-) disease to determine if age or nodal status influenced outcomes. Among women ≤50 years old, 5-year mets-free survival was 94% versus 89% with and without chemo, respectively. But among those >50 years old, it was 90% either way. Nodal status was not significantly associated with chemo benefit. With respect to age, one question is whether the chemo benefit seen among younger women was a direct chemo effect or indirect via ovarian suppression that was not otherwise administered.
TBL: Low genomic risk using the 70-gene Mammoprint signature indicates safe de-escalation to endocrine therapy alone even in the setting of high clinical risk and pN1 disease, though caution is warranted in women <50 years of age. | Piccart, Lancet Oncol 2021