4.7 Article

HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ

Journal

CANCER
Volume 118, Issue 17, Pages 4354-4362

Publisher

WILEY
DOI: 10.1002/cncr.26734

Keywords

ductal carcinoma in situ; breast cancer; cancer vaccine; dendritic cell vaccine; HER-2; neu

Categories

Funding

  1. National Institutes of Health [R01 CA096997]
  2. Harrington Foundation
  3. Pennies-in-action.org
  4. Mistler Foundation

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BACKGROUND: HER-2/neu overexpression plays a critical role in breast cancer development, and its expression in ductal carcinoma in situ (DCIS) is associated with development of invasive breast cancer. A vaccine targeting HER-2/neu expression in DCIS may initiate immunity against invasive cancer. METHODS: A HER-2/neu dendritic cell vaccine was administered to 27 patients with HER-2/neuoverexpressing DCIS. The HER-2/neu vaccine was administered before surgical resection, and pre- and postvaccination analysis was conducted to assess clinical results. RESULTS: At surgery, 5 of 27 (18.5%) vaccinated subjects had no evidence of remaining disease, whereas among 22 subjects with residual DCIS, HER-2/neu expression was eradicated in 11 (50%). When comparing estrogen receptor (ER)neg with ERpos DCIS lesions, vaccination was more effective in hormone-independent DCIS. After vaccination, no residual DCIS was found in 40% of ERneg subjects compared with 5.9% in ERpos subjects. Sustained HER-2/neu expression was found in 10% of ERneg subjects compared with 47.1% in ERpos subjects (P = .04). Postvaccination phenotypes were significantly different between ERpos and ERneg subjects (P = .01), with 7 of 16 (43.8%) initially presenting with ERposHER-2/neupos luminal B phenotype finishing with the ERposHER-2/neuneg luminal A phenotype, and 3 of 6 (50%) with the ERnegHER-2/neupos phenotype changing to the ERnegHER-2/neuneg phenotype. CONCLUSIONS: Results suggest that vaccination against HER-2/neu is safe and well tolerated and induces decline and/or eradication of HER-2/neu expression. These findings warrant further exploration of HER-2/neu vaccination in estrogen-independent breast cancer and highlight the need to target additional tumor-associated antigens and pathways. Cancer 2012. (c) 2012 American Cancer Society.

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