Skip to main content

Advertisement

SpringerLink
Log in

Response to HER-2 Pulsed DC1 Vaccines is Predicted by Both HER-2 and Estrogen Receptor Expression in DCIS

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Patients with estrogen-independent (ERneg) human epidermal growth factor receptor-2 (HER-2)-positive ductal carcinoma in situ (DCIS) treated with lumpectomy alone or lumpectomy and radiation are at increased risk of developing subsequent breast cancer events.

Methods

Thirty-eight patients with HER-2 expressing DCIS received a HER-2 pulsed autologous dendritic cell (DC1) vaccine administered over 4–6 weeks before surgical resection. HER-2 and estrogen receptor (ER) expression were determined by immunohistochemistry. In 35 patients, CD4pos T-cell sensitization to HER-2 peptides was identified by ELISPOT. In 19 patients, CD8pos T-cell responses were identified by ELISA. Clinical and immune responses postvaccination were compared between intermediate-expressing HER-2 (2+) and high-expressing HER-2 (3+) patients, as well as ERneg and estrogen-dependent (ERpos) patients.

Results

There was no significant difference in immune response after HER-2 vaccination in patients with HER-2 (2+) and (3+) tumors or ERneg and ERpos tumors. Complete tumor regression rates were similar in patients with HER-2 (2+) and (3+) DCIS. Overall, clinical response rates were similar in patients with ERneg and ERpos DCIS, but complete tumor regression was significantly more common in patients with ERneg DCIS.

Conclusions

Despite equivalent immune responses after vaccination in patients with HER-2 (2+), HER-2 (3+), ERneg and ERpos DCIS, HER-2 pulsed DC1 induces more complete responses in patients with ERneg DCIS. These data provide a rationale for developing vaccinations to reduce recurrence in patients with ERneg DCIS for whom there are currently limited adjuvant options.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Smigal C, Jemal A, Ward E, Cokkinides V, Smith R, Howe H, Thun M. Trends in breast cancer by race and ethnicity: update 2006. CA Cancer J Clin. 2006;56(3):168–83.

    Article  PubMed  Google Scholar 

  2. Wang GS, Zhu H, Bi SJ. Pathological features and prognosis of different molecular subtypes of breast cancer. Mol Med Report. 2012;6(4);779–82.

    Google Scholar 

  3. Koski G, Koldovsky U, Xu S, et al. A novel dendritic cell based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer. J Immunother. 2012;35(1):54–65.

    Article  PubMed  CAS  Google Scholar 

  4. Sharma A, Koldovsky U, Xu S, et al. (2012), HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ. Cancer. 2012;118(17):4354–4362.

    Article  PubMed  CAS  Google Scholar 

  5. Czerniecki B, Koski G, Koldovsky U, et al. Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion. Cancer Res. 2007;67:1842–1852.

    Article  PubMed  CAS  Google Scholar 

  6. Benavides LC, Gates JD, Carmichael MG, et al. The impact of HER2/neu expression level on response to the E75 vaccine: from U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clin Cancer Res. 2009;15(8):2895–2904.

    Article  PubMed  CAS  Google Scholar 

  7. Mittendorf EA, Clifton GT, Holmes JP, et al. Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients. Cancer. 2012;118(10):2594–2602.

    Article  PubMed  CAS  Google Scholar 

  8. Hackshaw A, Roughton M, Forsyth S, et al. Long-term benefits of 5 years of tamoxifen: 10-year follow-up of a large randomized trial in women at least 50 years of age with early breast cancer. J Clin Oncol. 2011;29(13):1657–1663.

    Article  PubMed  Google Scholar 

  9. O’Brien KM, Cole SR, Tse CK, et al. Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study. Clin Cancer Res. 2010;16:6100.

    Article  PubMed  Google Scholar 

  10. Bedrosian I, Mick R, Xu S, et al. Intranodal administration of peptide pulsed mature dendritic cell vaccines results in superior CD8 + T-cell function in melanoma patients. J Clin Oncol. 2003;21(20):3826–3835.

    Article  PubMed  CAS  Google Scholar 

  11. Xu S, Koski G, Faries M, et al. Rapid high efficiency sensitization of CD8 + T cells to tumor antigens by dendritic cells leads to enhanced functional avidity and direct tumor recognition through an IL-12 dependent mechanism. J Immunol. 2003;171(5):2251–2261.

    PubMed  CAS  Google Scholar 

  12. Kobayashi H, Wood M, Song Y, et al. Defining promiscuous MHC class II helper T cell epitopes for the HER-2/neu tumor antigen. Cancer Res. 2000;60:5228–5236.

    PubMed  CAS  Google Scholar 

  13. Knutson K, Schiffman K, Cheever M, et al. Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369–377, results in short-lived peptide specific immunity. Clin Cancer Res. 2002;8:1014–1018.

    PubMed  CAS  Google Scholar 

  14. Roses R, Paulson E, Sharma A, et al. HER-2/neu overexpression as a predictor for the transition from in situ to invasive breast cancer. Cancer Epidemiol Biomarkers Prev. 2009;18:1386–1389.

    Article  PubMed  CAS  Google Scholar 

  15. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004;10:909–915.

    Article  PubMed  CAS  Google Scholar 

  16. Palucka K, Ueno H, Banchereau J. Recent developments in cancer vaccines. J Immunol. 2011;186(3):1325–1331.

    Article  PubMed  CAS  Google Scholar 

  17. Cintolo JA, Datta J, Mathew SJ, Czerniecki BJ. Dendritic cell-based vaccines: barriers and opportunities. Future Oncol. 2012;8(10):1273–1299.

    Article  PubMed  CAS  Google Scholar 

  18. Keilholz U, Martus P, Scheibenbogen C. Immune monitoring of T-cell responses in cancer vaccine development. Clin Cancer Res. 2006;12:2346s–2352s.

    Article  PubMed  CAS  Google Scholar 

  19. Harada S, Mick R, Roses RE. The significance of HER-2/neu receptor positivity and immunophenotype in ductal carcinoma in situ with early invasive disease. J Surg Oncol. 2011;104:458–465.

    Article  PubMed  CAS  Google Scholar 

  20. Ithimakin S, Day KC, Malik F, et al. HER-2 drives luminal breast cancer stem cells in the absence of HER-2 amplification: implications for efficacy of adjuvant trastuzumab. Cancer Res. 2013;73(5):1635–1646.

    Article  PubMed  CAS  Google Scholar 

  21. Nahta R, O’Regan RM. Therapeutic implications of estrogen receptor signaling in HER2-positive breast cancers. Breast Cancer Res Treat. 2012;135:39–48.

    Article  PubMed  CAS  Google Scholar 

  22. Sabnis G, Schayowitz A, Goloubeva O, Macedo L, Brodie A. Trastuzumab reverses letrozole resistance and amplifies the sensitivity of breast cancer cells to estrogen. Cancer Res. 2009;69:1416–1428.

    Article  PubMed  CAS  Google Scholar 

  23. Xia W, Bacus S, Hegde P, et al. A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer. Proc Breast Cancer Res Treat. 2006;103(20):7795–7800.

    CAS  Google Scholar 

  24. Mittendorf EA, Wu Y, Scaltriti M, et al. Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic therapy and survival outcomes. Clin Cancer Res. 2009;15:7381-8.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

Dr. Czerniecki has licensing agreement with Immunocellular Therapeutics.

Author information

Authors and Affiliations

  1. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Megan Fracol BS

  2. Rena Rowan Breast Center, Penn Medicine, Philadelphia, PA, USA

    Shuwen Xu MD, Elizabeth Fitzpatrick BS, Harvey Nisenbaum MD, Robert Roses MD, Carla Fisher MD, Julia Tchou MD, PhD, Kevin Fox MD, Paul Zhang MD, PhD & Brian J Czerniecki MD, PhD

  3. Abramson Cancer Center, Penn Medicine, Philadelphia, PA, USA

    Shuwen Xu MD, Elizabeth Fitzpatrick BS, Harvey Nisenbaum MD, Robert Roses MD, Carla Fisher MD, Julia Tchou MD, PhD, Kevin Fox MD, Paul Zhang MD, PhD & Brian J Czerniecki MD, PhD

  4. Department of Surgery, Penn Medicine, Philadelphia, PA, USA

    Shuwen Xu MD, Elizabeth Fitzpatrick BS, Robert Roses MD, Carla Fisher MD, Julia Tchou MD, PhD & Brian J Czerniecki MD, PhD

  5. Department of Biostatistics and Epidemiology, Penn Medicine, Philadelphia, PA, USA

    Rosemarie Mick MS

  6. Department of Radiology, Penn Medicine, Philadelphia, PA, USA

    Harvey Nisenbaum MD

  7. Department of Medicine, Penn Medicine, Philadelphia, PA, USA

    Kevin Fox MD

  8. Department of Pathology, Penn Medicine, Philadelphia, PA, USA

    Paul Zhang MD, PhD

Authors
  1. Megan Fracol BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuwen Xu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rosemarie Mick MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elizabeth Fitzpatrick BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Harvey Nisenbaum MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert Roses MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carla Fisher MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Julia Tchou MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kevin Fox MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Paul Zhang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Brian J Czerniecki MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brian J Czerniecki MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fracol, M., Xu, S., Mick, R. et al. Response to HER-2 Pulsed DC1 Vaccines is Predicted by Both HER-2 and Estrogen Receptor Expression in DCIS. Ann Surg Oncol 20, 3233–3239 (2013). https://doi.org/10.1245/s10434-013-3119-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-013-3119-y

Keywords

Search

Navigation