HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ
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 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-2/neu 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(pos) HER-2/neu(pos) luminal B phenotype finishing with the ER(pos) HER-2/neu(neg) luminal A phenotype, and 3 of 6 (50%) with the ER(neg) HER-2/neu(pos) phenotype changing to the ER(neg) HER-2/neu(neg) 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.