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

Publication ,  Journal Article
Barroso-Sousa, R; Barry, WT; Guo, H; Dillon, D; Tan, YB; Fuhrman, K; Osmani, W; Getz, A; Baltay, M; Dang, C; Yardley, D; Moy, B; Marcom, PK ...
Published in: Ann Oncol
April 2019

BACKGROUND: Previous data suggest that the immune microenvironment plays a critical role in human epidermal growth factor receptor 2 (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 Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer (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 3cm. Exploratory analysis of tumor infiltrating lymphocytes (TIL), programmed death-ligand 1 (PD-L1) expression (by immunohistochemistry), and immune gene signatures using data generated by nCounter PanCancer Pathways Panel (NanoString Technologies, Seattle, WA), and their association with pathological and molecular characteristics was carried out. RESULTS: Of the 406 patients, 328 (81%) had at least one immune assay carried out: 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, histological 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, histological 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, histological grade, and molecular subtype. Further work is needed to explore the implication of these findings on disease outcome. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00542451.

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Published In

Ann Oncol

DOI

EISSN

1569-8041

Publication Date

April 2019

Volume

30

Issue

4

Start / End Page

575 / 581

Location

England

Related Subject Headings

  • Tumor Microenvironment
  • Tumor Burden
  • Trastuzumab
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Paclitaxel
  • Oncology & Carcinogenesis
  • Middle Aged
  • Mastectomy
  • Kaplan-Meier Estimate
 

Citation

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Barroso-Sousa, R., Barry, W. T., Guo, H., Dillon, D., Tan, Y. B., Fuhrman, K., … Tolaney, S. M. (2019). The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Ann Oncol, 30(4), 575–581. https://doi.org/10.1093/annonc/mdz047
Barroso-Sousa, R., W. T. Barry, H. Guo, D. Dillon, Y. B. Tan, K. Fuhrman, W. Osmani, et al. “The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial.Ann Oncol 30, no. 4 (April 2019): 575–81. https://doi.org/10.1093/annonc/mdz047.
Barroso-Sousa R, Barry WT, Guo H, Dillon D, Tan YB, Fuhrman K, et al. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Ann Oncol. 2019 Apr;30(4):575–81.
Barroso-Sousa, R., et al. “The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial.Ann Oncol, vol. 30, no. 4, Apr. 2019, pp. 575–81. Pubmed, doi:10.1093/annonc/mdz047.
Barroso-Sousa R, Barry WT, Guo H, Dillon D, Tan YB, Fuhrman K, Osmani W, Getz A, Baltay M, Dang C, Yardley D, Moy B, Marcom PK, Mittendorf EA, Krop IE, Winer EP, Tolaney SM. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Ann Oncol. 2019 Apr;30(4):575–581.
Journal cover image

Published In

Ann Oncol

DOI

EISSN

1569-8041

Publication Date

April 2019

Volume

30

Issue

4

Start / End Page

575 / 581

Location

England

Related Subject Headings

  • Tumor Microenvironment
  • Tumor Burden
  • Trastuzumab
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Paclitaxel
  • Oncology & Carcinogenesis
  • Middle Aged
  • Mastectomy
  • Kaplan-Meier Estimate