Omega-3 Fatty Acids in Preventing Joint Symptoms in Patients With Stage I-III Breast Cancer Receiving Anastrozole, Exemestane, or Letrozole

OBJECTIVES:

I. To assess the feasibility of evaluating joint symptoms in postmenopausal women with breast
cancer randomized to n-3 PUFA (omega-3 fatty acid) vs. placebo supplementation using the
Functional Assessment of Cancer Therapy-Breast (FACT-B) and endocrine subscale (FACT-ES),
Brief Pain Inventory (BPI) and Stanford's Health Assessment -Disability Index (HAS) during
the first 6 months of adjuvant aromatase inhibitor (AI) therapy.

II. To preliminarily evaluate the efficacy of n-3 PUFA vs. placebo supplementation on AI
induced joint symptoms.

III. To explore blood and imaging based biomarkers (plasma and red blood cell [RBC] levels of
n-3 PUFAs, inflammatory cytokines and receptors, and intra-articular tenosynovial
inflammation by musculoskeletal magnetic resonance imaging [MRI] imaging) of AI-induced joint
symptoms in women on AI therapy randomized to n-3 PUFAs vs. placebo supplementation.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive omega-3 fatty acid orally (PO) once daily (QD) for 6 months in the
absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO QD for 6 months in the absence of disease progression or
unacceptable toxicity.

Inclusion Criteria:

- Women diagnosed with breast cancer stages I-III initiating first adjuvant AI therapy
with any of the Food and Drug Administration- (FDA) approved AIs (anastrozole,
exemestane, letrozole)

- Concurrent gonadotropin-releasing hormone (GnRH) agonist therapy is allowed

- Concurrent breast related radiation therapy is allowed

- Prior tamoxifen use is allowed

- Prior chemotherapy is allowed

- History of osteoarthritis and/or fibromyalgia is allowed

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

Exclusion Criteria:

- Metastatic malignancy of any kind

- Rheumatoid arthritis and other types of autoimmune and inflammatory joint disease,
with the exception of osteoarthritis and fibromyalgia

- AI use > 2 weeks prior to study enrollment

- Known bleeding disorders

- History of diabetes mellitus, heart disease or TIA/stroke

- Current use of warfarin or other anticoagulants

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia,or psychiatric illness/social situation that would limit compliance with
study requirements

- Daily use of n-3 PUFA concentrates or capsules or regular or any other supplements
that might interact with n-3 PUFA supplements within six months of study initiation;
sporadic use of n-3 PUFA supplement may be eligible if there has been a 3-month
washout period prior to randomization

- Pregnant or nursing women

- Known sensitivity or allergy to fish or fish oil

- Concurrent use of daily full dose aspirin (≥ 325 mg/day), nonsteroidal
anti-inflammatory drugs (NSAIDs) or NSAID-containing products or steroids; one month
washout period is required prior to randomization

- Unable to give informed consent

- In patients consenting for optional MRIs, any contraindication to MRI examination
including but not limited to ferromagnetic metal in the body, pacemaker, or severe
claustrophobia