title: 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.
authors.affiliation: Rena Rowan Breast Center, Penn Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Anupama
authors.initials: A
authors.lastname: Sharma
authors.forename: Ursula
authors.initials: U
authors.lastname: Koldovsky
authors.forename: Shuwen
authors.initials: S
authors.lastname: Xu
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mick
authors.forename: Robert
authors.initials: R
authors.lastname: Roses
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fitzpatrick
authors.forename: Susan
authors.initials: S
authors.lastname: Weinstein
authors.forename: Harvey
authors.initials: H
authors.lastname: Nisenbaum
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Levine
authors.forename: Kevin
authors.initials: K
authors.lastname: Fox
authors.forename: Paul
authors.initials: P
authors.lastname: Zhang
authors.forename: Gary
authors.initials: G
authors.lastname: Koski
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Czerniecki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases