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Associations of HER2-specific immunity with survival during treatment with trastuzumab and chemotherapy in breast cancer.
Background: The addition of trastuzumab to chemotherapy improves response to therapy and extends survival among patients with HER2-positive (HER2+) breast cancer. Prior work showed that trastuzumab and chemotherapy also induces HER2 extracellular domain (ECD)-specific antibodies which correlate with tumor shrinkage. The present study investigates whether combination therapy induced immune responses to other tumor antigens and whether immune responses are associated with survival. Methods: Pretreatment and posttreatment sera were obtained from 54 women with metastatic HER2+ breast cancer on NCCTG (now Alliance for Clinical Trials in Oncology) studies N0337 and N983252. IgG to HER2, p53, IGFBP2, CEA and tetanus toxoid were examined using ELISAs. Sera from an age-matched group (25 patients) of controls and 26 HER2+ adjuvant patients were also examined. Results: Prior to therapy, some patients with metastatic disease had elevated IgG levels to IGFBP2, p53, HER2-ICD, HER2-ECD, and CEA, but not to tetanus toxin, relative to controls and adjuvant patients. Elevated preexisting immunity to HER2 was associated with significantly worse outcome (p < 0.003). Following therapy, increases in levels of IgG to IGFBP2, HER2-ICD, HER2-ECD, and p53 were observed in metastatic patients who did not have elevated preexisting immunity. Increased immunity to HER2 was associated with improved progression-free (p < 0.003) and overall survival (p < 0.04). Conclusions: Combination treatment results in induction of adaptive immunity to multiple antigens that contribute to disease outcome. If these results are validated, this could provide the basis for the development of biomarkers predictive of therapeutic benefit and the development of new therapeutic approaches with monoclonal antibodies.
Abstracts by Keith L. Knutson:
A phase I trial of the safety and immunogenicity of a multi-epitope folate receptor alpha peptide vaccine used in combination with cyclophosphamide in subjects previously treated for breast or ovarian cancer.Meeting: 2015 ASCO Annual Meeting | Abstract No: e14028
Meeting: 2015 ASCO Annual Meeting
| Abstract No: e22115
Category: Tumor Biology - Immunobiology