Flaxseed, Aromatase Inhibitors and Breast Tumor Characteristics
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional

Summary: 
      The proposed study plans to examine the effect of flaxseed consumption, a phytoestrogen rich
      food, compared to aromatase inhibitors as a complementary approach to treating estrogen
      receptor positive breast cancer, as well as the effect of combined flaxseed and aromatase
      inhibitor therapy on breast cancer treatment. Because of the increasing use of both
      complementary and alternative approaches to treatment, and the use of aromatase inhibitors in
      the treatment of breast cancer, the proposed study has potential to provide important
      clinical information about the effect of foods high in phytoestrogens on a common endocrine
      therapy used in breast cancer.
    

Detailed description: 
      Although the 10 year survival rate for women with early stage breast cancer is very good,
      distant recurrence is still a serious concern, especially for estrogen receptor positive
      women. Consequently, breast cancer survivors are interested in therapies that might improve
      their recurrence free survival (RFS). Used in postmenopausal women, aromatase inhibitors (AI)
      block the peripheral conversion of androgens to estrogen, effectively lowering the estradiol
      available to promote breast tumor proliferation. However, use of AIs is associated with hot
      flashes, joint pain, bone loss, and an increase in cardiac events. Furthermore, many breast
      tumors eventually develop resistance to hormonal treatments. Complementary and alternative
      medicines (CAMs) are widely used by cancer survivors in an attempt to reduce disease
      recurrence with fewer side effects and potential health benefits, and use is particularly
      prevalent among breast cancer survivors. Flaxseed (FS) is a commonly available food often
      consumed as a dietary supplement and is the richest food source of lignans, a phytoestrogen.
      In experimental models, flaxseed consumption has been shown to exhibit a number of activities
      that suggest a potential benefit of flaxseed in the adjuvant setting. However, the majority
      of human studies investigating the biologic effects of flaxseed have involved healthy women.
      There is a paucity of clinical data regarding the efficacy and safety of use of flaxseed
      among women with breast cancer, especially among those receiving AIs. Because the
      phytoestrogens in flaxseed can influence many of the same biologic pathways affected by
      hormonal agents, diet-drug interactions are possible. Additionally, it is possible flaxseed
      could act through growth and signaling pathways, modifying the development of endocrine
      resistance. Potential synergistic or antagonistic effects between flaxseed and antiestrogens
      are of particular interest given the increasing use of AIs to treat postmenopausal women with
      hormone responsive disease. We propose to conduct a pilot 2x2 factorial randomized
      intervention study between tumor biopsy and resection, in postmenopausal women diagnosed with
      ER positive breast cancer, to assess the effects of flaxseed and AI on a number of steroid
      hormone and tumor-related characteristics associated with long-term survival, and to
      investigate the potential interaction between flaxseed and AI on tumor expression of Ki-67,
      caspase, ERα, ERβ, PgR, HER2, IGF1, IGFIR. The pre-surgical setting offers a unique
      opportunity to rapidly obtain information on intervention related effects on growth factor
      and signaling pathways related to tumor characteristics in a short time period without the
      interference of other treatments. We hypothesize that both flaxseed and AI interventions will
      independently favorably affect growth factor and signaling pathway protein expression
      resulting in reduced tumor proliferation and increased apoptosis. We further hypothesize that
      these improvements will be reflected in improved recurrence scores as estimated by the
      Mammostrat antibody panel (Applied Genomics Incorporated). The proposed study will provide
      important clinical data for future dietary intervention studies involving phytoestrogen
      lignans from flaxseed.
    

Intervention name(s): Anastrozole; flaxseed; Placebo
Intervention type(s): Drug; Dietary Supplement; Drug
Intervention description(s): 1 mg per day; 25 g per day ground; Placebo pill 1 per day
Other intervention name(s): Arimidex
Intervention MeSH terms: Anastrozole
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: breast neoplasms; phytoestrogens; tumor characteristics; proliferation; apoptosis; estrogen receptor; HER2