The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial

Abstract

Background

Previous data suggest that the immune microenvironment plays a critical role in HER2-positive breast cancer, however there is little known about the immune profiles of small HER2-positive tumors. In this study we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the APT trial, and to correlate the immune markers with pathological and molecular tumor characteristics.

Patients and Methods

The APT trial was a multicenter, single-arm phase II study of paclitaxel and trastuzumab in patients with node-negative HER2-positive breast cancer. The study included 406 patients with HER2-positive, node-negative breast cancer, measuring up to 3 cm. Exploratory analysis of tumor infiltrating lymphocytes (TIL), PD-L1 expression (by immunohistochemistry), and immune gene signatures using data generated by nCounter PanCancer Pathways Panel (NanoString Technologies), and their association with pathological and molecular characteristics were performed.

Results

Of the 406 patients, 328 (81%) had at least one immune assay performed: 284 cases were evaluated for TIL, 266 for PD-L1, and 213 for immune gene signatures. High TIL (≥ 60%) were seen with greater frequency in hormone- receptor (HR) negative, grades 2 and 3, as well in HER2-enriched and basal-like tumors. Lower stromal PD-L1 (≤1%) expression was seen with greater frequency in HR positive, grade 1, and in luminal tumors. Both TIL and stromal PD-L1 were positively correlated with 10 immune cell signatures, including Th1 and B cell signatures. Luminal B tumors were negatively correlated with those signatures. Significant correlation was seen among these immune markers; however, the magnitude of correlation did not indicate a monotonic relationship between them.

Conclusion

Immune profiles of small HER2-positive breast cancers differ according to HR status, grade, and molecular subtype. Further work is needed to explore the implication of these findings on disease outcome.

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