Abstract 170P
Background
β2-adrenergic receptor (ADRB2) modulates immune activation, and may enhance the activity of trastuzumab in HER2-positive breast cancer cells. We assessed the impact of ADRB2 expression on the outcomes of patients enrolled on the NCCTG-N9831 trial.
Methods
NCCTG-N9831 compared chemotherapy (arm A) versus chemotherapy plus trastuzumab (arms B&C) as adjuvant treatment of HER2-positive early-stage breast cancer patients. Disease-free survival (DFS) was the primary endpoint. Gene expression data by DASL Assay were matched to patient’s characteristics. Median ADRB2 expression was assessed, with levels above median defined as ADRB2-high and below median as ADRB2-low. Stromal tumor-infiltrating lymphocytes (TILs) levels were correlated with ADRB2 expression. DFS curves were created by Kaplan Meier method; multivariate analyses were performed with Cox proportional hazard models.
Results
ADRB2 expression data were available for 1,282 patients (arm A [N=433]; arms B&C [N=849]), who were classified according to ADRB2 expression levels (ADRB2-high [N=944] and ADRB2-low [N=388]). Overall, ADRB2-high patients had a longer DFS than ADRB2-low patients (p=0.01). ADRB2-high was associated with a longer DFS in patients from arms B&C (p<0.01), but not in those from arm A (p=0.63). The addition of trastuzumab yielded a significant DFS improvement in ADRB2-high patients (DFS arms B&C versus arm A, p<0.01); whereas ADRB2-low patients did not benefit from trastuzumab (DFS arms B&C versus arm A, p=0.47). ADRB2 expression presented a direct correlation with TILs levels (r=0.24, p<0.001). High TILs levels were associated with a favorable prognosis in ADRB2-high patients (p=0.03), but not in ADRB2-low patients (p=0.12).
Conclusions
These results suggest that ADRB2 expression is associated with a favorable prognosis and could identify a subset of HER2-positive early-stage breast cancer patients who appear not to benefit from adjuvant trastuzumab.
Clinical trial identification
NCT00005970.
Editorial acknowledgement
Legal entity responsible for the study
North Central Cancer Treatment Group (NCCTG)-N9831 trial. NCCTG is now part of the Alliance for Clinical Trials in Oncology (Alliance).
Funding
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821, U10CA180882, and U24CA196171 (to the Alliance for Clinical Trials in Oncology). Genentech provided trastuzumab for this study. Also supported in part by funds from Genentech, Genomic Health, Breast Cancer Research Foundation; and Fondation Cancer Luxembourg (to F.R. and C.D.).
Disclosure
R. Caparica: Speaker Bureau/Expert testimony: Boehringer-Ingelheim; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Speaker Bureau/Expert testimony: Janssen; Travel/Accommodation/Expenses: Pfizer. A.H. Awada: Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: ESAI; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: MSD. M. Piccart: Honoraria (institution), Officer/Board of Directors: Radius; Honoraria (self), Honoraria (institution): AstraZeneca; Honoraria (self), Honoraria (institution): Lilly ; Honoraria (self), Honoraria (institution): MSD; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self): Odonate; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (self), Honoraria (institution): Roche; Honoraria (self): Crescendo biologics; Honoraria (self): Periphagen; Honoraria (self): Huya; Honoraria (self): Debiopharm; Honoraria (self): PharmaMar; Honoraria (self): G1 therapeutics; Honoraria (self): Menarini; Honoraria (self): Seattle Genetics; Honoraria (self): Immunomedics; Honoraria (institution): Synthon; Honoraria (institution): Servier. E. Perez: Honoraria (institution): NIH; Honoraria (institution): Roche. A. Moreno-Aspitia: Honoraria (institution): NIH; Honoraria (institution): Roche. S. Badve: Speaker Bureau/Expert testimony: Targos; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Natera; Honoraria (institution): Dako/Agilent; Honoraria (institution): Roche/Ventana. E. de Azambuja: Honoraria (self), Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Glaxo. All other authors have declared no conflicts of interest.