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Clinical Trial
. 2022 Mar 8;114(3):467-470.
doi: 10.1093/jnci/djab057.

Tumor Cellularity and Infiltrating Lymphocytes as a Survival Surrogate in HER2-Positive Breast Cancer

Nuria Chic  1   2   3 , Stephen J Luen  4 , Paolo Nuciforo  5 , Roberto Salgado  6   7 , Debora Fumagalli  8 , Florentine Hilbers  8 , Yingbo Wang  9 , Evandro de Azambuja  10   11 , István Láng  12 , Serena Di Cosimo  3   13 , Cristina Saura  3   14 , Jens Huober  15 , Aleix Prat  1   2   3   16   17 , Sherene Loi  4
Affiliations
Clinical Trial

Tumor Cellularity and Infiltrating Lymphocytes as a Survival Surrogate in HER2-Positive Breast Cancer

Nuria Chic et al. J Natl Cancer Inst. .

Abstract

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.

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Figures

Figure 1.
Figure 1.
Survival outcomes in NeoALTTO based on CelTIL score. A) Event-free survival (EFS) based on the CelTIL prespecified cutoff score. B) Overall survival (OS). C) EFS based on CelTIL tertile groups. D) OS based on CelTIL tertile groups. E) EFS in patients with a pathological complete response (pCR). F) EFS in patients with a non-pCR. Estimates of EFS and OS were from Kaplan-Meier curves and tests of differences by Cox proportional hazards model. All statistical tests were 2 sided. CelTIL = score based on tumor cellularity and tumor infiltrating lymphocytes at day 14; CI = confidence interval; HR = hazard ratio.
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References

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