Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

PRIMARY OBJECTIVES:

I. To determine whether treatment with docosahexaenoic acid (DHA) for 12 weeks at 1000 mg
twice daily as compared to placebo reduces normal breast tissue levels of tumor necrosis
factor-alpha (TNF-alpha) in overweight and obese patients with a history of stage I-III
invasive breast cancer, ductal carcinoma in situ (DCIS), Paget's disease, lobular carcinoma
in situ (LCIS), or proliferative benign breast disease.

SECONDARY OBJECTIVES:

I. To investigate the effect of DHA at 1000 mg twice daily on tissue biomarkers

- Change from the baseline in cyclooxygenase-2 (COX-2)/interleukin-1-beta
(IL-1beta)/aromatase measured by quantitative real-time polymerase chain reaction
(PCR).

- Change from the baseline in crown-like structures of the breast (CLS-B) measured by
immunohistochemical techniques for cluster of differentiation (CD)68.

- Change from baseline in CLS-B index determined as follows: ([number of slides with
evidence of at least one CLS-B]/[total number of slides examined]).

- Change from baseline in CLS-B/cm^2 defined as the number of CLS-B/cm^2. II. Evaluate
age as a predictor of CLS-B and inflammatory biomarkers (TNF-alpha/COX-2/IL-1beta) at
baseline and over the time of treatment.

III. Evaluate red blood cell (RBC) fatty acid level as a surrogate of compliance.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive docosahexaenoic acid orally (PO) twice daily (BID) for 12 weeks.

ARM II: Patients receive placebo PO BID for 12 weeks.

Inclusion Criteria:

- Participants must have a history of histologically-confirmed stage I-III invasive
breast cancer or ductal carcinoma in situ (DCIS), Paget's disease, lobular carcinoma
in situ (LCIS), or proliferative benign breast disease

- No evidence of disease (in situ or invasive cancer that would normally be treated by
resection) at trial entry as determined by the investigator

- >= 6 months from all previous breast cancer treatment (including surgery for invasive
cancer, chest wall radiotherapy, chemotherapy, trastuzumab and endocrine therapy)

- Participants must have a body mass index (BMI) >= 25, defined as (weight in
kilograms/[height in meters]^2)

- Participants must have adequate accessible breast tissue as determined by the
treating physician, consisting of one breast unaffected by invasive cancer, which has
not been radiated; a history of prior pre-invasive breast cancer or benign biopsy of
this breast will be permitted

- Daily DHA consumption =< 200 mg/day in the month prior to screening estimated by an
abbreviated DHA food frequency questionnaire

- Mammogram within no more than 6 months prior to the date of informed consent
(normal/benign Breast Imaging-Reporting and Data System [BI-RADS] 1 or 2) and no
further routine breast imaging planned during the course of the study (12 weeks
DHA/placebo)

- Eastern Cooperative Oncology Group (ECOG) performance status must be =< 2 (Karnofsky
>= 60%)

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 75,000/uL

- White blood cells >= 3,000/uL

- Hemoglobin >= 10 g/dL

- Total bilirubin within 1.5 times the institution's upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
within 1.5 times the institution's ULN

- Serum creatinine within 1.5 times the institution's ULN

- Pregnant women will be excluded; for women of childbearing potential; negative
pregnancy testing within 72 hours prior to or on study visit #1 (day 0) and
willingness to use adequate contraception during the study intervention OR
post-menopausal defined as any one of the following 1) prior hysterectomy, 2) absence
of menstrual period for 1 year in the absence of prior chemotherapy or 3) absence of
menstrual period for 2 years in women with a prior history of chemotherapy exposure
who were pre-menopausal prior to chemotherapy

- Willingness to comply with all study interventions and follow-up procedures including
the ability to swallow the study drug

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

Exclusion Criteria:

- Any type of active invasive cancer (excluding breast and non-melanoma skin cancer)
within the preceding 18 months

- A history of histologically-confirmed bilateral invasive breast cancer

- Bilateral mastectomy

- Prior history or evidence of metastatic breast cancer

- Prior radiation therapy to the contralateral (unaffected) breast

- Prior history of contralateral (unaffected) breast augmentation with breast implant
placement

- History of daily use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) in
the week preceding study entry

- History of DHA supplementation > 200 mg/day in the month preceding study entry

- History of autoimmune disorder or any illness that requires therapy with chronic
steroids or immunomodulators

- History of therapeutic doses of anticoagulants including warfarin and low molecular
weight heparin (e.g. for prior deep venous thrombosis and pulmonary embolism) in the
preceding year

- Participants may not be receiving any other investigational agents during the study

- Women who have received cancer surgery, chemotherapy, biological therapy (e.g.,
trastuzumab), or radiotherapy for the treatment of any cancer within 6 months of
study participation

- Women who are receiving endocrine therapy for breast cancer treatment or
chemoprevention including tamoxifen, letrozole, anastrozole, fulvestrant, or
exemestane at the time of screening

- Individuals with severe underlying chronic illness, such as uncontrolled diabetes;
ongoing or active infection, psychiatric illness or social situations which in the
opinion of the investigator would interfere with study participation

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to DHA or corn/soy oil in placebo agent

- Pregnant, breastfeeding, or women of childbearing potential unwilling to use a
reliable contraceptive method