Research ArticleBreast Cancer

Preclinical and Clinical Evaluation of Intraductally Administered Agents in Early Breast Cancer

Science Translational Medicine  26 Oct 2011:
Vol. 3, Issue 106, pp. 106ra108
DOI: 10.1126/scitranslmed.3002368

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Repairing the Ductwork

Breast cancer is typically treated intravenously with chemotherapeutic drugs, poisons that permeate the entire body and cause toxic side effects, such as hair loss, pain, and nausea. Because most breast tumors originate in the cellular lining of the breast ducts, Stearns and colleagues designed a gentler, more local treatment regimen that gets right to the source: intraductal drug injection.

The authors first tested intraductal treatment with five different chemotherapeutic agents, including paclitaxel and doxorubicin, on rats with mammary tumors, at doses comparable to what might be used in the clinic in actual patients. Compared to saline-treated or untreated control animals, the rats treated intraductally had fewer tumors in the mammary glands, with minimal side effects. Stearns et al. then enrolled 17 women in a phase 1 clinical trial to examine intraductal treatment using one chemical agent, pegylated liposomal doxorubicin. Their localized delivery to the breast ducts resulted in considerably lower systemic concentrations of the drug compared to intravenous administration, suggesting that the intraductal approach is a less toxic alternative to standard chemotherapy. This clinical trial also indicates that approved agents can be delivered to the breast ducts in an outpatient setting. Longer-term studies in more women will be necessary to determine the efficacy of intraductal chemotherapy.

Intraductal treatment could be especially useful for women with premalignant lesions or those at high risk of developing breast cancer, thus drastically improving upon their other, less attractive options of breast-removal surgery or surveillance (termed “watch and wait”). It’s not yet routine practice, but direct treatment of the breast ductwork with cancer-fighting drugs promises to be a safer, less painful method for controlling cancer.

Footnotes

  • * These authors contributed equally to this work.

  • Present address: Department of Surgery, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.

  • § Present address: Cancer Center of the Rockies, 2121 East Harmony Road, Suite 150, Fort Collins, CO 80528, USA.