title: Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer.
abstract: OBJECTIVE
  Skin metastases of breast cancer remain a therapeutic challenge. Toll-like receptor 7 agonist imiquimod is an immune response modifier and can induce immune-mediated rejection of primary skin malignancies when topically applied. Here we tested the hypothesis that topical imiquimod stimulates local antitumor immunity and induces the regression of breast cancer skin metastases.
  
  
  METHODS
  A prospective clinical trial was designed to evaluate the local tumor response rate of breast cancer skin metastases treated with topical imiquimod, applied 5 d/wk for 8 weeks. Safety and immunologic correlates were secondary objectives.
  
  
  RESULTS
  Ten patients were enrolled and completed the study. Imiquimod treatment was well tolerated, with only grade 1 to 2 transient local and systemic side effects consistent with imiquimod's immunomodulatory effects. Two patients achieved a partial response [20%; 95% confidence interval (CI), 3%-56%]. Responders showed histologic tumor regression with evidence of an immune-mediated response, showed by changes in the tumor lymphocytic infiltrate and locally produced cytokines.
  
  
  CONCLUSIONS
  Topical imiquimod is a beneficial treatment modality for breast cancer metastatic to skin/chest wall and is well tolerated. Importantly, imiquimod can promote a proimmunogenic tumor microenvironment in breast cancer. Preclinical data generated by our group suggest superior results with a combination of imiquimod and ionizing radiation and we are currently testing in patients whether the combination can further improve antitumor immune and clinical responses.
authors: Departments of Medicine, New York University School of Medicine, New York, New York 10016, USA. sylvia.adams@nyumc.org
authors: Sylvia
authors: S
authors: Adams
authors: Lina
authors: L
authors: Kozhaya
authors: Frank
authors: F
authors: Martiniuk
authors: Tze-Chiang
authors: TC
authors: Meng
authors: Luis
authors: L
authors: Chiriboga
authors: Leonard
authors: L
authors: Liebes
authors: Tsivia
authors: T
authors: Hochman
authors: Nicholas
authors: N
authors: Shuman
authors: Deborah
authors: D
authors: Axelrod
authors: James
authors: J
authors: Speyer
authors: Yelena
authors: Y
authors: Novik
authors: Amy
authors: A
authors: Tiersten
authors: Judith D
authors: JD
authors: Goldberg
authors: Silvia C
authors: SC
authors: Formenti
authors: Nina
authors: N
authors: Bhardwaj
authors: Derya
authors: D
authors: Unutmaz
authors: Sandra
authors: S
authors: Demaria
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D000077271:Imiquimod; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D016207:Cytokines; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D000077271:Imiquimod