Intraductal Therapy of DCIS: A Presurgery Study

Institution: Dr. Susan Love Research Foundation
Investigator(s): Susan  Love , M.D., M.B.A. -
Award Cycle: 2007 (Cycle 13) Grant #: 13OB-0185 Award: $851,559
Award Type: Translational Research Award
Research Priorities
Innovative Treatments>Gene therapy and other treatments: new frontiers



Initial Award Abstract (2007)
Ductal Carcinoma In Situ (DCIS), an early stage, non-invasive breast cancer, is treated with the same methods of surgery, radiation and hormone medications as more advanced forms. Historical studies show that most DCIS remains dormant and only 30-40% of cases will ever progress to invasive cancer. As more women are being diagnosed by mammography with this pre-cancer, which is not life-threatening, they are asking why they should be subjected to the more extreme treatments. The breast ducts are the microscopic pipelines that bring milk down to the nipple during breast feeding. Breast cancer starts in the epithelial cells that form the thin lining on the surface of the ducts, like tiles. With advances in technology it is possible to enter the duct system through the nipple and by procedure called ductoscopy to visualize the interior of the duct system. As an extension of this “intraductal approach” it is possible to introduce drugs or other agents into the duct system to destroy or reset the abnormal cells that are present in women bearing DCIS lesions. This novel treatment strategy may eventually save countless women from undergoing mutilating surgery and debilitating treatments.

The aim of this project is to test the practicality and efficacy of a local treatment of the affected breast duct itself. We plan to use a currently approved drug, called Pegylated Liposomal Doxorubicin or PLD, by introducing it directly into the ductal system bearing DCIS lesions. In preliminary studies, our collaborators have tested this drug in rodents and humans for side effects. In rat studies, the intraductal administration of PLD can eradicate breast cancer at low doses and without the systemic side-effects seen with treatments administered via the IV (blood) route. Preliminary studies have shown that intraductal PLD is well tolerated in women, but we do not have studies demonstrating efficacy in treating DCIS.

In this study, women who have been diagnosed with DCIS on the basis of an abnormal mammogram and a biopsy (a stereotactic core) done by the radiologist will be referred to our trial. A breast PET scan and ductal lavage will be done before the treatment for a baseline. The woman will then have the duct with DCIS cannulated and a small amount of contrast material will be placed to make sure the correct duct is being treated. Then, the PLD will be introduced into the duct. Surgery will be planned for 4-6 weeks later. A day or two prior to surgery imaging tests, such as mammography and PET scans, of the breast will be repeated. The type of surgery to be done will not be affected by participation in the study. After surgery, the pathology will be studied and the women followed by their breast surgeon for at least two years, as usual. If indicated, patients will be referred for consultation with medical and/or radiation oncologists.

This will be the first observational study of intraductal therapy. It can open a new era in the management of breast cancer, especially the earliest DCIS stages where women are typically over-treated.


Progress Report 1 (2008)
Ductal carcinoma in situ (DCIS) is an early stage, non-invasive breast cancer where the cells are still confined within the limits of the milk duct. While less than half the cases of DCIS will progress, the increasing numbers of women diagnosed with this disease are still being treated with the more drastic methods of surgery, radiation and hormone medications as are more advanced invasive forms.

The Dr. Susan Love Research Foundation’s (DSLRF) mission is to eradicate breast cancer and Dr. Love has pioneered the intraductal approach to prevention and treatment. This translational grant was funded to look at the safety and feasibility of using a currently approved chemotherapy drug, called Pegylated Liposomal Doxorubicin or PLD locally in the breast. In rat studies, the intraductal administration of PLD can eliminate breast cancer at low doses and without the systemic side-effects seen with treatments given via the IV (blood) route. Preliminary studies have shown that intraductal PLD is well tolerated in women, but we do not have studies demonstrating its effectiveness, particularly with DCIS. Besides the surgical pathology endpoints we will also be looking at markers in ductal fluid and changes on MRI imaging before and after treatment.

As this is the first study of its kind, most of the first year has been spent informing hospital administration and medical staff about the study and acquainting the Humboldt County community at large about the project. Dr. Ellen Mahoney met with representatives from St. Joseph Hospital’s IRB for several meetings to familiarize them with the study, answer their questions, respond to their concerns and develop an informed consent form to their satisfaction. The DSLRF staff also traveled to Eureka to meet with the medical community particularly the radiology staff. A mock-up of what a subject would need to do was carried out at that time. It was also determined that as Naviscan is unable to provide a breast PET Scan for our study at this time we are going to use MRI for imaging. An independent Data and Safety Monitoring Board has been recruited and will be holding its first meeting shortly.

We have been publicizing the trial in local newspapers and it is now listed on www.clinicaltrials.gov. and www.breastcancertrials.org. A local oncology nurse has been hired and has been reviewing potential pathology reports and patients. While interest appears high, to date, unfortunately women have not met the eligibility criteria or had other time commitments. Dr. Love and Mahoney will be giving a public talk arranged by the Humboldt Community Breast Health Project on June 19th. We expect this to increase awareness and enthusiasm for the study. With the administrative hurdles overcome, we look forward to enrolling our first patient shortly in this exciting, ground breaking trial.


Progress Report 2 (2009)
As this is the first study of its kind, most of the first year was spent informing hospital administration and medical staff about the study and acquainting the Humboldt County Community at large about the project. IRB approval was obtained in December of 2007. Local publicity and enthusiasm for this study has continued into Year 2. The Data Safety Monitoring Committee had its first meeting via teleconference in November of 2008.

The first subject was recruited in July of 2008 and 8 others have signed consent forms and been enrolled to date. Five subjects have had the Doxil instilled and undergone their planned surgery 6 weeks later. The remaining 4 did not have the drug instilled due to technical problems with drug cannulation and/ or perforation of the duct on ductogram. While there have been some reports of moderate tenderness and redness of the breast, all five women who had the drug instilled completed the 6 week observation time. The grant’s Data Safety Monitoring Committee is meeting later in June, 2009 to review all of the subjects’ CRF’s, radiographic imaging and pathology to date. Protocol changes will be recommended at this time and resubmitted to the St. Joseph Hospital IRB which recently contracted with Western IRB.