Beta-2 Adrenergic Receptor Gene Expression in HER2-Positive Early-Stage Breast Cancer Patients: A Post-hoc Analysis of the NCCTG-N9831 (Alliance) Trial

Rafael Caparica, Yaohua Ma, Claudia De Angelis, François Richard, Christine Desmedt, Ahmad Awada, Martine Piccart, Edith A. Perez, Alvaro Moreno-Aspitia, Sunil Badve, E. Aubrey Thompson, Evandro de Azambuja

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Beta-2 adrenergic receptor (ß2AR) modulates immune activation and may enhance trastuzumab activity. We assessed the impact of ß2AR gene (ADRB2) expression on the outcomes of patients with HER2-positive early-stage breast cancer enrolled on the NCCTG-N9831 trial. Patients and Methods: This is a post-hoc analysis of the NCCTG-N9831 trial, which compared chemotherapy (arm A) versus chemotherapy plus trastuzumab (arms B&C) as adjuvant treatment of patients with HER2-positive early-stage breast cancer, with disease-free survival (DFS) as primary endpoint. Gene expression levels retrieved by DASL assay were used to classify patients as ADRB2-high or ADRB2-low. Hazard ratios (HRs) were calculated by a Cox proportional model adjusted for prognostic variables and ADRB2 expression. Correlations between ADRB2 expression and stromal tumor-infiltrating lymphocyte (TIL) levels were assessed with Pearson coefficient. A multivariable Cox regression model with interaction term was performed to assess the interaction between ADRB2 expression and treatment arm; and ADRB2 expression and a 8-gene signature previously shown to predict trastuzumab benefit. Results: Overall, 1,282 patients were included (ADRB2-high [N = 944] / ADRB2-low [N = 338]). A high expression of ADRB2 was associated with a longer DFS (P =.01) in the overall population. The addition of trastuzumab to chemotherapy improved DFS only in patients with ADRB2-high tumors (P <.01). ADRB2 expression was correlated with TIL levels (r = 0.24, P <.001). No association between ADRB2 expression and the 8-gene trastuzumab benefit signature was observed (P =.32). Conclusion: Our findings suggest that a high ADRB2 expression is a favorable prognostic factor and may identify patients with HER2-positive early-stage breast cancer who benefit from adjuvant trastuzumab. Trial Registration: clinicaltrials.gov NCT00005970

Original languageEnglish (US)
JournalClinical breast cancer
DOIs
StateAccepted/In press - 2022

Keywords

  • ADRB2
  • Beta-2 adrenergic receptor
  • Breast cancer
  • HER2
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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