Imiquimod for Breast Cancer. Skin Metastases. TO THE EDITOR:Henriques et al1 recently published a case report demonstrating successful treatment of ...
VOLUME
32
䡠
NUMBER
28
䡠
OCTOBER
1
2014
JOURNAL OF CLINICAL ONCOLOGY
C O R R E S P O N D E N C E
Clinical Trial Evidence of the Antitumor Activity of Topical Imiquimod for Breast Cancer Skin Metastases TO THE EDITOR: Henriques et al1 recently published a case report demonstrating successful treatment of refractory breast cancer skin metastases with topical imiquimod added to systemic therapy. Application of imiquimod, a Toll-like receptor 7 agonist, resulted in partial regression of the skin metastases. The authors state in their introduction that a literature review only revealed a “single case report describing the use of topical imiquimod . . . to successfully treat breast cancer skin metastasis.”1(pe22) In 2012, we published a phase II trial of topical imiquimod in the treatment of breast cancer skin metastasis which included extensive correlative studies in tumor biopsies and blood.2 Imiquimod was applied five times per week as in the regimen approved for the treatment of superficial basal cell carcinoma and used in the previous case report of breast cancer.3 Similar to the report by Henriques et al,1 patients in the trial had the option to continue receiving a systemic regimen concurrently (if no previous response in skin was seen). The results of our prospective study showed that imiquimod treatment in women with heavily pretreated and refractory breast cancer skin metastases achieved a response rate of 20% (partial response in two of 10 patients). Changes in the tumor microenvironment of the responders were strongly suggestive of an immune-mediated response. We observed an induction of a Th1-polarized immune response as well as a reduction of a preexisting immunosuppressive milieu. Our results from a prospective trial demonstrate that imiquimod can be effective in patients with breast cancer that is metastatic to skin. However, the majority of tumors did not regress, which has important implications for future research. Combinatorial approaches should be tested to increase local response and to induce a more powerful antitumor immune response that is capable of controlling systemic metastases, as visceral disease ultimately causes the patient’s death. Preliminary evidence of systemic disease control has been observed in two patients from the imiquimod trial who experienced long-lasting complete remissions after immuno-endocrine therapy, accompanied by treatment-induced priming and boosting of tumor antigen–specific T cells, detectable ex vivo (manuscript submitted for publication).
To inform clinical studies, our group and others have studied and identified synergistic combinations in murine models of mammary carcinoma. In the TSA murine model of breast cancer with cutaneous involvement, the combination of topical imiquimod and local radiotherapy induced complete regression of the treated lesions and improved systemic tumor control, leading to enhanced survival.4 Improved antitumor efficacy and prolonged survival was also observed in neu transgenic mice, in which topical imiquimod was combined with antibodies against interleukin-10.5 Clinical trials are ongoing to study these and other combinations (NCT01421017 and NCT00821964).
Sylvia Adams, Yelena Novik, Ruth Oratz, Deborah Axelrod, and James Speyer New York University School of Medicine, New York, NY
Amy Tiersten Mount Sinai School of Medicine, New York, NY
Judith D. Goldberg New York University School of Medicine, New York, NY
Nina Bhardwaj Mount Sinai School of Medicine, New York, NY
Derya Unutmaz, Sandra Demaria, and Silvia Formenti New York University School of Medicine, New York, NY
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. Henriques L, Palumbo M, Guay MP, et al: Imiquimod in the treatment of breast cancer skin metastasis. J Clin Oncol 32:e22-e25, 2014 2. Adams S, Kozhaya L, Martiniuk F, et al: Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer. Clin Cancer Res 18:6748-6757, 2012 3. Hengge UR, Roth S, Tannapfel A: Topical imiquimod to treat recurrent breast cancer. Breast Cancer Res Treat 94:93-94, 2005 4. Dewan MZ, Vanpouille-Box C, Kawashima N, et al: Synergy of topical toll-like receptor 7 agonist with radiation and low-dose cyclophosphamide in a mouse model of cutaneous breast cancer. Clin Cancer Res 18:6668-6678, 2012 5. Lu H, Wagner WM, Gad E, et al: Treatment failure of a TLR-7 agonist occurs due to self-regulation of acute inflammation and can be overcome by IL-10 blockade. J Immunol 184:5360-5367, 2010
DOI: 10.1200/JCO.2014.56.1282; published online ahead of print at www.jco.org on August 4, 2014
■ ■ ■
3204
© 2014 by American Society of Clinical Oncology
Journal of Clinical Oncology, Vol 32, No 28 (October 1), 2014: pp 3204-3205
Downloaded from jco.ascopubs.org on October 18, 2015. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.
Correspondence
2014 Breast Cancer Symposium Join us for the 2014 Breast Cancer Symposium, Thursday, September 4 through Saturday, September 6, 2014, in San Francisco, CA. Designed to facilitate cross-disciplinary learning, this year’s meeting will offer an ideal opportunity to share ideas with leaders in the field. Take advantage of this unique chance to showcase your research, strengthen your collaborative work, and engage in networking opportunities. For more information, visit breastcasym.org.
www.jco.org
© 2014 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on October 18, 2015. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.
3205
