title: Response to HER-2 pulsed DC1 vaccines is predicted by both HER-2 and estrogen receptor expression in DCIS.
abstract: BACKGROUND
  Patients with estrogen-independent (ER(neg)) 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.
  
  
  METHODS
  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, CD4(pos) T-cell sensitization to HER-2 peptides was identified by ELISPOT. In 19 patients, CD8(pos) 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 ER(neg) and estrogen-dependent (ER(pos)) patients.
  
  
  RESULTS
  There was no significant difference in immune response after HER-2 vaccination in patients with HER-2 (2+) and (3+) tumors or ER(neg) and ER(pos) 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 ER(neg) and ER(pos) DCIS, but complete tumor regression was significantly more common in patients with ER(neg) DCIS.
  
  
  CONCLUSIONS
  Despite equivalent immune responses after vaccination in patients with HER-2 (2+), HER-2 (3+), ER(neg) and ER(pos) DCIS, HER-2 pulsed DC1 induces more complete responses in patients with ER(neg) DCIS. These data provide a rationale for developing vaccinations to reduce recurrence in patients with ER(neg) DCIS for whom there are currently limited adjuvant options.
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Fracol
authors.forename: Shuwen
authors.initials: S
authors.lastname: Xu
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mick
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fitzpatrick
authors.forename: Harvey
authors.initials: H
authors.lastname: Nisenbaum
authors.forename: Robert
authors.initials: R
authors.lastname: Roses
authors.forename: Carla
authors.initials: C
authors.lastname: Fisher
authors.forename: Julia
authors.initials: J
authors.lastname: Tchou
authors.forename: Kevin
authors.initials: K
authors.lastname: Fox
authors.forename: Paul
authors.initials: P
authors.lastname: Zhang
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Czerniecki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007114:Immunization; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000276:immunology / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D019496:Cancer Vaccines; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C506487:ESR1 protein, human; C508053:ERBB2 protein, human