Cancer is a disease of excess. Cells become malignant when they lose the signals that tell them to stop growing and dividing; therefore, the cells most susceptible to becoming cancerous are those that are already used to proliferating. Whereas most neurons last a lifetime, epithelial cells (found in the skin as well as intestinal and ductal linings) replicate often: the skin is renewed every two months and intestinal epithelium every 3-6 days. Due to this rapid growth, as well as the fact that these cells are more often exposed to chemical or physical damage, 80-90 percent of human malignancies originate from epithelial cells (think about skin cancer) and are referred to as carcinomas.
The same is true of breast cancers, which frequently arise from mutations in the epithelial cells lining the lactiferous ducts that connect the mammary glands to the skin surface, i.e. nipple. Treatment options often are limited to removal of the breast (prophylactic mastectomy) or years of estrogen therapy (e.g. tamoxifen). The problem with the latter option is that it affects the whole body and commonly leads to negative side effects such as nausea, blood clots, stroke, and uterine cancer.
A new treatment option may soon be available thanks to the work of an interdisciplinary team of clinicians and bench researchers at the Johns Hopkins School of Medicine. Led by the directors of the Hopkins Breast Cancer Program, Vered Stearns and Saraswati Sukumar, the team hypothesized that administration of agents directly into the breast ductal system through the nipple (intraductal) could prevent the development of new tumors or the progression of preinvasive neoplasms. Following tests of this theory in both an animal model and phase 1 clinical trial, their promising results are summarized well in the Editors note preceding their paper in Science Translational Medicine:
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.
According to the press release from Johns Hopkins:
The goal is to use intraductal therapy to suppress tumors in patients with a high genetic risk for breast cancer or premalignant lesions in their breast ducts. In principle, one could do such a procedure every ten years or so to keep ones breasts tumor-free, as an alternative to having the breasts removed, Sukumar says.
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Tags: Cancer, Intraductal Delivery
