Tumorcellulariteit en TILs als overlevingssurrogaat bij HER2-positief mammacarcinoom

In early-stage HER2-positive breast cancer, biomarkers that guide deescalation and/or escalation of systemic therapy are needed. CelTIL score is a novel, combined biomarker based on stromal tumor-infiltrating lymphocytes and tumor cellularity and is determined in tumor biopsies at week 2 of anti-HER2 therapy only. We evaluated the prognostic value of CelTIL in 196 patients with early-stage HER2-positive disease treated with standard trastuzumab-based chemotherapy in the NeoALTTO phase III trial. Using a prespecified CelTIL cutoff, a better 5-year event-free survival and overall survival was observed between CelTIL-high and CelTIL-low score with a 76.4% (95% confidence interval [CI] = 68.0% to 85.0%) vs 59.7% (95% CI = 50.0% to 72.0%) (hazard ratio = 0.40, 95% CI = 0.17 to 0.94) and 86.4% (95% CI = 80.0% to 94.0%) vs 73.5% (95% CI = 64.0% to 84.0%) (hazard ratio = 0.43, 95% CI = 0.20 to 0.92), respectively. Statistical significance was maintained after adjusting for baseline tumor-infiltrating lymphocytes, hormone receptor status, pretreatment tumor size and nodal status, type of surgery, treatment arm, and pathological complete response. Further studies to support CelTIL as an early readout biomarker to help deescalate or escalate systemic therapy in HER2-positive breast cancer seem warranted.