A Pilot Pre-operative Window Trial of Black Cohosh in Women With Ductal Carcinoma in Situ

The overarching hypothesis of our research is that black cohosh has potential to be a
well-tolerated, effective agent for the treatment of early breast cancer. This pilot study
represents a first step in exploring this hypothesis by demonstrating preliminary evidence
of specific anti-tumor effect of black cohosh on areas of ductal carcinoma in situ (DCIS) in
the breast.

Inclusion Criteria:

- A patient/subject is eligible for enrollment if all of the following inclusion
criteria are met:

1. Pre- and post-menopausal women ≥ 18 years of age newly diagnosed with DCIS
histologically confirmed on breast core biopsy

2. Ability to understand and the willingness to sign a written informed consent
document

3. ECOG performance status 0-1

4. Life expectancy >12 months

5. Willing to schedule definitive resection of DCIS 4 weeks +/- 1 week after study
enrollment

6. Original breast core biopsy specimen available for pathologic review and
staining by Yale School of Medicine Department of Pathology

Exclusion Criteria:

- A patient /subject will not be eligible for this study if any of the following
exclusion criteria are met:

1. Pregnant or nursing within past 6 months

2. Lactose intolerant, lactose allergy or salicylate allergy

3. Patients who have already undergone excisional biopsy for qualifying DCIS

4. Patients with ipsilateral treatment for DCIS or breast cancer within 12 months
prior to entering this study

5. Patients receiving any other chemotherapy or investigational agents

6. Serious concomitant systemic disorders (including active infections) or
psychiatric illness/social situations that would compromise the safety of the
patient or compromise the patient's ability to complete the study, at the
discretion of the investigator.

7. Liver function tests ≥ 20% of the institutional upper limits of normal

8. Creatinine > 1.5 times the institutional upper limit of normal

9. ANC < 1,500 /µL

10. Platelets < 100,000 /µL

11. History of allergic reactions attributed to compounds of similar chemical or
biologic composition to black cohosh

12. The effects of black cohosh on the developing human fetus at the recommended
therapeutic dose are unknown. For this reason, women of child-bearing potential
must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) for the duration of study participation. Should a woman
become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately.

13. Prior/concurrent therapy including:

Tamoxifen, raloxifene, letrozole, anastrozole, or exemestane in the past 6
months

14. Chemotherapy, biologic therapy (e.g., trastuzumab [Herceptin®]), or breast
radiotherapy to the breast currently affected by DCIS within the past 12 months

15. Any exogenous hormonal therapy including estrogen-, progesterone-, and/or
androgen-based agents in the past 6 months

16. Phytoestrogens or OTC medications with estrogenic or androgenic properties in
the past 6 months

17. Any black cohosh preparation within the past 6 months