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Flaxseed vs. Aromatase Inhibitors: Breast Tumor Characteristics and Prognosis

Phase 0
18 Years
85 Years
Open (Enrolling)
Breast Cancer

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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.

Inclusion Criteria:

- Age ≥ 18 and ≤ 85 years

- Postmenopausal status defined as: no menstrual cycle in the past 12 months
hysterectomy with bilateral oophorectomy hysterectomy with intact ovaries if age > 55

- Newly diagnosed with incident, primary, invasive, estrogen receptor positive clinical
stage II or lower breast cancer

- ECOG performance status of 1 or less

- Willingness to comply with study guidelines and procedures

- Willingness and ability to provide informed consent

- Usual consumption of soy no more than 1 time per week and willingness to avoid whole
soy foods or concentrated soy sources (soy milk, tofu, substitute meat products, meal
replacement bars) during the intervention period

- Willingness to avoid herbal and dietary supplements (not including vitamins),
aspirin, and ibuprofen during the intervention period

- No competing neoadjuvant or chemotherapy treatment

- Time between pre-surgical visit and surgery must be at least 2 weeks

- No chemotherapy in the past 12 months

Exclusion Criteria:

- Inability to read and write English

- Previous invasive breast cancer

- Insulin dependent Type I or II diabetes diagnosed by physician

- History of coagulopathy, thrombocytopenia, or bleeding disorder

- Current (past 30 days) regular (at least once per week) use of reproductive hormone
therapy, Tamoxifen, aromatase inhibitors, or other estrogen inhibitors, flaxseed, or

- Current chemotherapy or neoadjuvant chemotherapy

- Allergies to flaxseed, nuts, or other seeds

- Renal dysfunction defined as creatinine > 1.5 mg/dl

- History of Crohns' disease, ulcerative colitis, irritable bowel syndrome, celiac
sprue, or other malabsorption syndrome, diverticulitis, diverticulosis, or other
bowel diagnosis which, in the opinion of the breast surgeon, would contraindicate
large doses of dietary fiber or would impair nutrient absorption

- Current, regular (more than once weekly) use of prescription blood-thinning agents
including coumadin, heparin and heparin related drugs, clopidogrel bisulfate

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Outcome Measure:

tumor characteristics, proliferation and apoptosis, ER, PR, HER2 expression

Outcome Time Frame:

biopsy and surgical resection

Safety Issue:


Principal Investigator

Tracey L O'Connor, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Food and Drug Administration

Study ID:

I 99507



Start Date:

November 2007

Completion Date:

Related Keywords:

  • Breast Cancer
  • breast neoplasms
  • phytoestrogens
  • tumor characteristics
  • proliferation
  • apoptosis
  • estrogen receptor
  • HER2
  • Breast Neoplasms



Roswell Park Cancer Institute Buffalo, New York  14263