Brian J Czern
Scientific Tracks Abstracts: J Vaccines Vaccin
ntroduction: HER-2/neu over-expression in breast cancer is associated with high risk of recurrence and poorer outcomes. HER-2/neu expression has been identifi ed in breast cancer stem cells. Elimination of HER-2/neu-expressing ce lls may therefore improve breast cancer outcomes. Methods: Twenty-seven patients with HER-2/neu over-expressing ductal carcinoma in situ (DCIS) were enrolled in a phase I neoadjuvant trial to determine whether HER-2/neu peptide- pulsed DC vaccines were safe and could e liminate HER-2/neu over-expressing cells. Pre- and post- vaccination immune monitoring and histopathological analysis were conducted to assess results. Results: Post-immunization, anti-HER-2/neu CD4 pos and CD8 pos T cells were identifi ed in >88% of subjects, with evidence of durable (>2 yr) responses and inter-molecular epitope spreading. Five of 27 (18.5%) vaccinated subjects had no evidence of remaining disease. Detectable HER-2/neu was eliminated (i.e. immunoedited) in 11 of 22 (50%) patients with residual DCIS. Comparing the 10 ERneg with the17 ER pos subjects we observed: no residual DCIS in 40% vs. 5.9% of patients, and sustained HER-2/neu expression in 10% vs. 47.1%, suggesting vaccination was more eff ective against hormone-independent DCIS (p=0.04). Post- vaccination DCIS phenotypes also diff ered signifi cantly between ERpos and ER neg subjects (p=0.01). Seven of 16 patients (43.8%) initially presenting with the more aggressive ER pos HER- 2/neu pos phenotype demonstrated ER pos HER-2/neu neg phenotype aft er vaccination, while 3 of 6 (50%) starting with ER neg HER-2/neu pos DCIS became ER neg HER-2/neu neg . Conclusions: Th is targeted immunoediting approach appeared eff ective for reducing HER-2/neu-expressing cells in DCIS, suggesting that targeting HER-2/neu and other stem cell- associated molecules should be explored for preventing primary and recurrent breast cancer.