Addition of anti-estrogen therapy to anti-HER2 dendritic cell vaccination improves regional nodal immune response and pathologic complete response rate in patients with ERpos/HER2pos early breast cancer. Academic Article uri icon

Overview

abstract

  • HER2-directed therapies are less effective in patients with ERpos compared to ERneg breast cancer, possibly reflecting bidirectional activation between HER2 and estrogen signaling pathways. We investigated dual blockade using anti-HER2 vaccination and anti-estrogen therapy in HER2pos/ERpos early breast cancer patients. In pre-clinical studies of HER2pos breast cancer cell lines, ERpos cells were partially resistant to CD4+ Th1 cytokine-induced metabolic suppression compared with ERneg cells. The addition of anti-estrogen treatment significantly enhanced cytokine sensitivity in ERpos, but not ERneg, cell lines. In two pooled phase-I clinical trials, patients with HER2pos early breast cancer were treated with neoadjuvant anti-HER2 dendritic cell vaccination; HER2pos/ERpos patients were treated with or without concurrent anti-estrogen therapy. The anti-HER2 Th1 immune response measured in the peripheral blood significantly increased following vaccination, but was similar across the three treatment groups (ERneg vaccination alone, ERpos vaccination alone, ERpos vaccination + anti-estrogen therapy). In the sentinel lymph nodes, however, the anti-HER2 Th1 immune response was significantly higher in ERpos patients treated with combination anti-HER2 vaccination plus anti-estrogen therapy compared to those treated with anti-HER2 vaccination alone. Similar rates of pathologic complete response (pCR) were observed in vaccinated ERneg patients and vaccinated ERpos patients treated with concurrent anti-estrogen therapy (31.4% vs. 28.6%); both were significantly higher than the pCR rate in vaccinated ERpos patients who did not receive anti-estrogen therapy (4.0%, p = 0.03). Since pCR portends long-term favorable outcomes, these results support additional clinical investigations using HER2-directed vaccines in combination with anti-estrogen treatments for ERpos/HER2pos DCIS and invasive breast cancer.

authors

  • Lowenfeld, Lea
  • Zaheer, Salman
  • Oechsle, Crystal
  • Fracol, Megan
  • Datta, Jashodeep
  • Xu, Shuwen
  • Fitzpatrick, Elizabeth
  • Roses, Robert E
  • Fisher, Carla S
  • McDonald, Elizabeth S
  • Zhang, Paul J
  • DeMichele, Angela
  • Mick, Rosemarie
  • Koski, Gary K
  • Czerniecki, Brian J

publication date

  • July 1, 2016

Identity

PubMed Central ID

  • PMC5599079

Scopus Document Identifier

  • 85028553640

Digital Object Identifier (DOI)

  • 10.1080/01621459.1958.10501452

PubMed ID

  • 28932627

Additional Document Info

volume

  • 6

issue

  • 9