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Breast Ducts: A New Site for Cancer Treatment
January 31, 2006
Johns Hopkins Kimmel Cancer Center researchers are studying whether delivering chemotherapy drugs directly to breast "plumbing" might make treatment of early breast cancer easier on the patient and at least as good as surgery or radiation.
A report on successful tests of intraductal therapy in rats and mice published in the January 15 issue of Cancer Research has paved the way for one of the first preliminary clinical trials in women with breast cancer.
Since most breast cancers begin in the cells lining the milk ducts, Dr. Saraswati Sukumar, a professor of oncology at Johns Hopkins is exploring the possibility of treating ductal carcinoma in situ (DCIS) by using hair-thin catheters to inject chemotherapy through openings in the nipple directly into the place where cancer starts—the milk ducts. The hope is that this treatment will be easier on the patient and at least as good as surgery or radiation.
This trial is enrolling women with breast cancer scheduled for a mastectomy at Johns Hopkins. The women are given intraductal chemotherapy before their mastectomy to test the safety and effectiveness of giving chemotherapy in this fashion. The breast is then examined to determine the effect of the intraductal therapy.
Sukumar likens the procedure to pouring detergent down the kitchen sink to rid the pipes of unwanted material. Because early breast cancers are less likely to have escaped the ducts, intraductal therapy may have at least as good a chance to cure as radiation or surgery. Standard treatments for DCIS, a pre-cancer that may develop into breast cancer, include radiation and surgery to remove the tumor via a lumpectomy or mastectomy. Chemotherapy, reserved for disease that has spread beyond the ducts, is not typically used to treat DCIS because conventional methods of delivering the drugs intravenously through an arm or chest vein would unnecessarily send the toxic chemicals coursing throughout the entire body.
Building on observations made by her lab on rat models using drugs that block estrogen, Sukumar began tests in mouse models three years ago by using a chemotherapy drug called doxorubicin. The mice were bred to develop breast cancers that were genetically similar to treatment-resistant ones in humans. The study found that injecting chemotherapy directly into the mouse mammary ducts (the mouse equivalent of a breast duct) was more effective than giving the chemotherapy intravenously.
Sukumar also believes that injecting chemotherapy agents or prevention drugs like tamoxifen into the breast ducts could be one option for women at high risk for the disease.
Phase I studies in breast cancer patients have begun to test the feasibility and safety of the procedure. Among the potential side effects that Sukumar's team will be studying in the trial are pain, inflammation, and changes in the structure of the duct network. Other areas for study include image-guided injections that could be rigged as "duct-detectors" to help pinpoint early lesions, as well as different chemotherapy drugs and dosing schedules.
Dr. Sukumar has worked with the Dr. Susan Love and the Foundation for more than 14 years. Two members of her research team, Regina Brown, MD, and Scott Kaminsky, PhD, received grants [link to E.2] from the Foundation in 2005 to conduct portions of the studies described above.
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