Effect of Flutamide on Biomarkers in Blood and Tissue Samples From Patients at High Risk of Ovarian Cancer

OBJECTIVE: Compare the biomarkers of patients at high risk for ovarian cancer who are
undergoing prophylactic oophorectomy and are interested in taking flutamide vs patients at
high risk for ovarian cancer who are undergoing prophylactic oophorectomy and are not
interested in taking flutamide (control) vs patients who are undergoing oophorectomy for a
medical indication (control).

OUTLINE: Patients who elected not to receive flutamide received prophylactic oophorectomy or
oophorectomy for a medical indication. Patients who elected to receive flutamide received
125mg once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent
prophylactic oophorectomy. All patients underwent blood and ovarian tissue sample collection
at the time of surgery for biomarker laboratory studies. Proteomic, microarray, and
polymorphism analysis were performed on the blood and tissue samples.

Inclusion Criteria for all patients:

- ≥ 18 years of age

- Able to comply with study and follow-up requirements

Inclusion Criteria for high risk patients:

- elected to undergo prophylactic salpingo-oophorectomy

- fertile patients must use effective non-hormonal contraception

- agreed to use a nonhormonal means of contraception before surgery

- serum bilirubin ≤ 1.0 x Upper Limit Normal (ULN), alkaline phosphatase, Aspartate
Aminotransferase (AST), and Alanine Aminotransferase (ALT) ≤ 2.5 x ULN

- serum creatinine ≤ 1.5 x ULN

- granulocyte count ≥ 1500/μL

- platelet count ≥ 75,000/μL

- hemoglobin ≥ 9 g/dL

- adequate complete blood count

- At high risk for developing ovarian cancer, as defined by any of the following:

- Breast Cancer carried a BRCA1 or BRCA2 deleterious mutation, a Lynch syndrome
mutation, and/or defined by a family history of: 1 first-degree relative with
epithelial ovarian cancer, ≥1 first-degree female relative with breast cancer when ≤40
years old, ≥1 first-degree female relative with breast cancer when ≤50 years old, male
relative with breast cancer, and/or family history of breast cancer or ovarian cancer.

Inclusion Criteria for low risk patients:

- planning to undergo oophorectomy for a medical indication

- did not fulfill criteria for high risk of developing ovarian cancer

Exclusion criteria:

- liver disease, current alcohol abuse, or cirrhosis

- pregnancy or lactation

- current use of hormone therapy

- active treatment for cancer

- recent, current, or planned participation in another experimental drug study

- breast cancer within the past 5 years

- significant traumatic injury within the past 6 months

- major surgery within the past 6 months

- any disease, physical examination findings, or clinical laboratory findings giving
reasonable suspicion of a disease or condition that contraindicates the continued use
of an investigational drug or that may render the patient at high risk from treatment
complication