Response to HER-2 Pulsed DC1 Vaccines is Predicted by Both HER-2 and Estrogen Receptor Expression in DCIS
- 386 Downloads
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.
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.
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.
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.
KeywordsLuminal Breast Cancer Complete Tumor Regression Exact Confidence Interval ERneg Patient Immune Response Rate
Dr. Czerniecki has licensing agreement with Immunocellular Therapeutics.
- 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
- 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.Google Scholar