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

Prevention of Aromatase Inhibitor-Induced Joint Symptoms With Omega 3 Fatty Acid Supplementation: a Randomized Placebo Controlled Pilot Study

This randomized pilot trial studies omega-3 fatty acid in preventing joint symptoms in patients with stage I-III breast cancer receiving anastrozole, exemestane, or letrozole. Omega-3 fatty acid supplement may lessen or prevent joint stiffness or pain in patients receiving hormone therapy for breast cancer.

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