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

摘要

Background: HER-2eu 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-2eu expression in DCIS may initiate immunity against invasive cancer. Methods: A HER-2eu dendritic cell vaccine was administered to 27 patients with HER-2eu-overexpressing DCIS. The HER-2eu 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-2eu expression was eradicated in 11 (50%). When comparing estrogen receptor (ER) neg with ER pos DCIS lesions, vaccination was more effective in hormone-independent DCIS. After vaccination, no residual DCIS was found in 40% of ER neg subjects compared with 5.9% in ER pos subjects. Sustained HER-2eu expression was found in 10% of ER neg subjects compared with 47.1% in ER pos subjects (P =.04). Postvaccination phenotypes were significantly different between ER pos and ER neg subjects (P =.01), with 7 of 16 (43.8%) initially presenting with ER posHER-2eu pos luminal B phenotype finishing with the ER posHER-2eu neg luminal A phenotype, and 3 of 6 (50%) with the ER negHER-2eu pos phenotype changing to the ER negHER-2eu neg phenotype. Conclusions: Results suggest that vaccination against HER-2eu is safe and well tolerated and induces decline and/or eradication of HER-2eu expression. These findings warrant further exploration of HER-2eu vaccination in estrogen-independent breast cancer and highlight the need to target additional tumor-associated antigens and pathways.