Immune-related gene expression signatures provide more prognostic value than tumor-infiltrating lymphocytes (TILs) for patients with early-stage HER2-positive breast cancer, according to research published in JAMA Oncology

The immune signatures were superior to TILs for predicting pathologic complete response (pCR) and event-free survival (EFS), researchers found.

The researchers tested the prognostic value of gene signatures and TILs using data from the CALGB 40601 trial ( Identifier: NCT00770809) and the PAMELA trial ( Identifier: NCT01973660). 

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The CALGB 40601 trial included 305 patients with stage II-III, HER2-positive breast cancer. They were randomly assigned to receive weekly neoadjuvant paclitaxel with trastuzumab, lapatinib, or both for 16 weeks. Immune-related gene expression signatures and TILs were assessed in 230 pretreatment tumors. 

The PAMELA trial included 151 patients with stage I-IIIA, HER2-positive breast cancer. They were treated with neoadjuvant trastuzumab and lapatinib for 18 weeks. Immune-related gene expression signatures and TILs were assessed in 138 pretreatment tumors. 

Of the 202 immune signatures tested, 166 (82.2%) were significantly correlated with TILs in both trials. 

Among patients from both trials, TILs were significantly associated with pCR (odds ratio, 1.01 for each 1% increase in TILs; 95% CI, 1.01-1.02; P =.02). This association was seen regardless of the trial or the treatment received. 

A total of 36 immune signatures (17.8%) were significantly associated with pCR, regardless of the trial or treatment. Seven of these signatures outperformed TILs for predicting pCR. Six of the 7 signatures were B-cell related. 

In a multivariable analysis, the immunoglobulin G (IgG) signature was independently associated with EFS (hazard ratio [HR], 0.63; 95% CI, 0.42-0.93; P =.02), but TILs were not (HR, 1.00; 95% CI, 0.98-1.02; P = .99).

The IgG signature and TILs together were more prognostic than TILs alone but not more prognostic than the IgG signature alone.

“Results of this study suggest that multiple B-cell-related signatures were more strongly associated with pCR and EFS than TILs,” the researchers concluded. “When both TILs and gene expression are available, the prognostic value of immune-related signatures appears to be superior.” 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Fernandez-Martinez A, Pascual T, Singh B, et al. Prognostic and predictive value of immune-related gene expression signatures vs tumor-infiltrating lymphocytes in early-stage ERBB2/HER2-positive breast cancer: A correlative analysis of the CALGB 40601 and PAMELA trials. JAMA Oncol. Published online January 5, 2022. doi:10.1001/jamaoncol.2022.6288 

This article originally appeared on Cancer Therapy Advisor