In a study reported in JAMA Oncology, Aranzazu Fernandez-Martinez, MD, PhD, and colleagues found that several B-cell–related gene signatures provided better prediction of pathologic complete response and event-free survival than tumor-infiltrating lymphocyte (TIL) levels among patients with early-stage, HER2-positive breast cancer enrolled in the CALGB 40601 and PAMELA trials.
Study Details
In the study, immune-related gene expression profiling with RNA sequencing and TIL levels were assessed in pretreatment tumors from 230 patients in CALGB 40601 and 138 patients in PAMELA. In CALGB 40601, patients were randomly assigned to neoadjuvant treatment with paclitaxel with trastuzumab, lapatinib, or both for 16 weeks; in PAMELA, patients received neoadjuvant treatment with trastuzumab and lapatinib for 18 weeks.
Aranzazu Fernandez-Martinez, MD, PhD
The current analysis assessed the association of immune signatures and TILs with pathologic complete response in patients from both trials and with event-free survival in those from CALGB 40601.
Key Findings
Of 202 immune signatures tested, 166 were significantly correlated with TILs.
In patients from both trials combined, the percentage of TILs as a continuous variable was significantly associated with higher pathologic complete response rate (odds ratio = 1.01, 95% confidence interval [CI] = 1.01–1.02, P = .02).
A total of 36 immune signatures were also significantly associated with higher pathologic complete response rates. Of these, seven were better at predicting pathologic complete response vs TILs, with six being B-cell–related signatures.
In an event-free survival analysis, the top-performing immune signatures also included B-cell–related signatures that outperformed TILs. In multivariate analysis adjusting for clinical and pathologic factors (including PAM50 intrinsic tumor subtype), an immunoglobulin G signature was independently associated with event-free survival (hazard ratio [HR] = 0.63, 95% CI = 0.42–0.93, P = .02), whereas no significant association of TIL levels was observed (HR = 1.00, 95% CI = 0.98–1.02, P = .99).
The investigators concluded, “Results of this study suggest that multiple B-cell–related signatures were more strongly associated with [pathologic complete response] and event-free survival than TILs, which largely represent T cells. When both TILs and gene expression are available, the prognostic value of immune-related signatures appears to be superior.”
Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the National Cancer Institute, The Breast Cancer Research Foundation, Susan G. Komen, and others. For full disclosures of the study authors, visit jamanetwork.com.
