DC Vaccine for Patients With Ductal Carcinoma In Situ

The treatment of patients with DCIS can be individualized and tailored to the type of DCIS
and the relative risk of the lesion. HER-2/neu over-expressing DCIS represents a group of
patients with significant risk for development of invasive breast cancer. In this proposal we
will continue to evaluate the development of type I polarized DC for the treatment of DCIS by
evaluating whether further improvements in therapeutic response can be achieved by
intratumoral administration of HER-2/neu pulsed DC1 compared with our current intranodal
administration. Women who are diagnosed with Her-2/neu over-expressing DCIS with no invasive
carcinoma will be eligible for this study. Patients will receive DC1 vaccines by intranodal,
intralesional, or both routes of administration. The primary objective will be safety and
administration with secondary objectives of immune activation and clinical response. We will
also develop a novel assay to monitor ongoing immunity to HER-2/neu, and lastly will begin to
develop these vaccines for patients with invasive breast cancer as well. Fifty-four subjects
will be randomized to one of three treatment arms: intranodal injection, intralesional
injection, or intranodal and intralesional injection of the vaccine. Upon entering this
study, the subjects' blood will be drawn in a way that collects only the white blood cells.
Subjects then receive six vaccines over a six week period. They will then undergo the
standard surgical procedure to remove any remaining DCIS in the breast.

Inclusion Criteria:

- Age > 18 years.

- Subjects with biopsy-proven DCIS, DCIS with microinvasion, DCIS with invasive disease
under 5 mm, or Paget's Disease of the nipple (DCIS of the nipple) who have not yet
received definitive treatment.

- HER-2/neu positive tumor as determined by >5% of tumor population expressing this
marker by immunohistochemical staining 2+ using anti-HER-2/neu verified by Dr. Paul
Zhang in the Department of Pathology.

- Women of childbearing age with a negative pregnancy test documented prior to
enrollment.

- Subjects with ECOG Performance Status Score of 0 or 1 (Appendix D).

- Subjects willing to use birth control if necessary

- Subjects who have voluntarily signed a written Informed Consent in accordance with
institutional policies after its contents have been fully explained to them.

Exclusion Criteria:

- Pregnant or lactating females (pregnancy testing to be performed within 7 days prior
to administration of first dose of vaccine).

- Subjects who have had a complete excisional biopsy of their tumor.

- Subjects with suspicion of invasive disease > 5mm by MRI performed within 2 months of
study recruitment.

- Screen and exclude subjects with positive HIV or hepatitis C at baseline.

- Subjects with coagulopathies, including thrombocytopenia with platelet count <75,000,
INR > 1.5 and partial thromboplastin time > 50 sec

- Subjects with major cardiac illness MUGA < 50% EF.

- Subjects with pre-existing medical illnesses or medications which might interfere with
the study.

- Subjects with laboratory tests reflecting ¬> grade 1 toxicity by NCI CTC version 3.0
including CBC, liver function tests, urinalysis, EKG if cannot be corrected on repeat
test in 7 days.