Topical TLR7 agonist and radiotherapy in patients with metastatic breast cancer

This study explores the safety and efficacy of combining topical Imiquimod (IMQ), a TLR-7 agonist, with local radiotherapy (RT) for metastatic breast cancer. The phase I/II clinical trial (NCT01421017) aimed to assess systemic and local anti-tumor responses using immune-related response criteria (irRC). Patients were divided into three cohorts: (1) IMQ + RT + cyclophosphamide, (2) IMQ + RT, and (3) RT + cyclophosphamide (control). Cutaneous metastases were treated with IMQ+RT (area A) or IMQ alone (area B). Tumor biopsies were obtained at baseline and after treatment for gene expression profiling. Results demonstrated safety and promising systemic anti-tumor responses, with transcriptional analyses revealing a T-helper 1 immune orientation and DNA-repair gene downregulation associated with complete responses in IMQ+RT-treated areas. The study involved longitudinal transcriptional analysis of tumor biopsies from 24 patients treated with topical IMQ (cohorts 1 and 2) and 7 control patients treated with RT alone (cohort 3). Tumor samples were collected at baseline, week 2, and week 3 post-treatment. Gene expression profiling was performed using Affymetrix microarrays to identify immune activation and DNA repair signatures associated with treatment response. A total of 84 samples were processed for transcriptional analyses. Submitter states: raw data not available for this series due to file loss.