Trial Information

Flaxseed vs. Aromatase Inhibitors: Breast Tumor Characteristics and Prognosis

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.