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

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

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Article numbere1207032
JournalOncoImmunology
Volume6
Issue number9
DOIs
StatePublished - Sep 2 2017
Externally publishedYes

Keywords

  • Breast cancer
  • estrogen
  • HER2
  • immunotherapy
  • sentinel lymph nodes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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