Sulindac in Preventing Breast Cancer in Women at High Risk for Breast Cancer

Phase IB Sulindac Study for Women at High Risk for Breast Cancer

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of sulindac may prevent breast cancer.

PURPOSE: This randomized phase I trial is studying the effects of sulindac, to prevent breast cancer, in women at high risk for breast cancer.

OBJECTIVES:

Primary

• Determine the partitioning of sulindac and its metabolites in women at high risk for breast cancer by measuring drug and metabolite levels in nipple aspirate fluid (NAF) after 6 weeks of therapy.

Secondary

• Determine prostaglandin levels in the NAF of patients treated with this drug.
• Determine if NAG-1 levels are induced in the NAF of patients treated with this drug.
• Determine if C-reactive protein levels are reduced in the NAF of patients treated with this drug.
• Determine if NAG-1 levels and/or karyometric features in ductal epithelial cells are modulated in patients treated with this drug.

OUTLINE: This is a randomized, open-label study.

Patients undergo nipple aspirate fluid (NAF) collection. Patients are then randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral sulindac once daily.
• Arm II: Patients receive oral sulindac twice daily. In both arms, treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. All patients then undergo a second NAF collection.

After completion of study treatment, patients are followed at 2 weeks.

PROJECTED ACCRUAL: A total of 30 patients (15 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Meets 1 of the following criteria:

  • Gail assessment score > 1.7% risk for 5 years
  • History of lobular carcinoma in situ (pathology report required)
  • History of ductal carcinoma in situ (DCIS) (pathology report required)
  • History of breast cancer in ≥ 1 first-degree relative or history of BRCA1 or BRCA2 positivity not treated with oophorectomy or mastectomy (test report required)
  • History of breast cancer in ≥ 2 second-degree relatives
  • Any family history of breast cancer diagnosed prior to age 50
  • Personal history of breast cancer (invasive or DCIS) with 1 breast intact

• Nipple aspirate fluid production ≥ 5 microliters

• Negative mammogram for breast cancer within the past 10 months

  • Any suspicious breast masses must be examined by a clinical professional

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Sex

• Female

Menopausal status

• Pre- or postmenopausal

Performance status

• Karnofsky 80-100%

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No history of bleeding or clotting disorder

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• AST and ALT ≤ 2.0 times upper limit of normal
• No indication of abnormal liver function

Renal

• Creatinine normal

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• No frequent, chronic, or moderate/severe gastric complaint
• No upper gastrointestinal problems (e.g., symptoms of heartburn, dyspepsia, or abdominal pain) requiring prescription or nonprescription medical remedies more than once per week (on average)
• No history of peptic ulcer or occult or gross intestinal bleeding

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reaction (e.g., urticaria, asthma, rhinitis) or gastric intolerance attributed to compounds of similar chemical or biological composition to sulindac
• No history of allergy attributed to lidocaine, EMLA® cream, or xylocaine
• No concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No more than 2-3 servings of alcohol per week during study participation

PRIOR CONCURRENT THERAPY:

Chemotherapy

• More than 6 months since prior chemotherapy for breast cancer (invasive or DCIS)

Endocrine therapy

• More than 6 months since prior hormonal therapy for breast cancer (invasive or DCIS)
• No concurrent hormone-suppressing agents (e.g., tamoxifen or anastrozole)
• No concurrent selective estrogen-receptor modulators
• No concurrent aromatase inhibitors

Radiotherapy

• More than 6 months since prior radiotherapy for breast cancer (invasive or DCIS)

Surgery

• See Disease Characteristics
• No prior breast duct-disrupting surgery (e.g., mastectomy) that would preclude ductoscopy

Other

• More than 3 months since prior warfarin or other systemic anticoagulant
• More than 4-6 weeks since prior nonsteroidal anti-inflammatory drugs
• No concurrent phenytoin or sulfonamides
• No concurrent warfarin or other systemic anticoagulant
• No other concurrent nonsteroidal anti-inflammatory drugs (including low-dose aspirin)
• No concurrent large doses of supplements, vitamins (> regular daily multivitamin) and/or herbal medicines (e.g., echinacea, ginkgo biloba, Hypericum perforatum [St. John's wort], or herbal tea)
• No other concurrent investigational agents