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

Authors

  • Anupama Sharma MD,

    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Surgery, Penn Medicine, Philadelphia, Pennsylvania
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  • Ursula Koldovsky PhD,

    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Surgery, Penn Medicine, Philadelphia, Pennsylvania
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  • Shuwen Xu MD,

    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Surgery, Penn Medicine, Philadelphia, Pennsylvania
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  • Rosemarie Mick MS,

    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Biostatistics and Epidemiology, Penn Medicine, Philadelphia, Pennsylvania
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  • Robert Roses MD,

    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Surgery, Penn Medicine, Philadelphia, Pennsylvania
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  • Elizabeth Fitzpatrick BS,

    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Surgery, Penn Medicine, Philadelphia, Pennsylvania
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  • Susan Weinstein MD,

    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Radiology, Penn Medicine, Philadelphia, Pennsylvania
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  • Harvey Nisenbaum MD,

    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Radiology, Penn Medicine, Philadelphia, Pennsylvania
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  • Bruce L. Levine MD,

    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Medicine, Penn Medicine, Philadelphia, Pennsylvania
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  • Kevin Fox MD,

    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Pathology, Penn Medicine, Philadelphia, Pennsylvania
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  • Paul Zhang MD, PhD,

    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Medicine, Penn Medicine, Philadelphia, Pennsylvania
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  • Gary Koski PhD,

    1. Department of Biological Sciences, Kent State University, Kent, Ohio
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  • Brian J. Czerniecki MD, PhD

    Corresponding author
    1. Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania
    2. Abramson Cancer Center, Penn Medicine, Philadelphia, Pennsylvania
    3. Department of Surgery, Penn Medicine, Philadelphia, Pennsylvania
    • Department of Surgery, 3 Perelman, 3400 Civic Center Drive, Philadelphia, PA 19104

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Abstract

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/neu–overexpressing 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. © 2012 American Cancer Society.

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