Flaxseed, Aromatase Inhibitors and Breast Tumor Characteristics (FABrC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00612560
Recruitment Status : Completed
First Posted : February 11, 2008
Results First Posted : August 16, 2017
Last Update Posted : October 12, 2017
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

February 7, 2008
February 11, 2008
July 17, 2017
August 16, 2017
October 12, 2017
November 2007
January 2011   (Final data collection date for primary outcome measure)
  • Expression of Estrogen Receptor (ER-beta) [ Time Frame: Biopsy/Week 1 and Surgical Resection/Week 2 ]
    Mean percentage of cells expressing estrogen receptor (ER-beta)
  • Progesterone Receptor (PR) Expression [ Time Frame: Biopsy/Week 1 and Surgical Resection/Week 2 ]
    Mean percentage of cells expressing PR
  • Human Epidermal Growth Factor Receptor 2 (Her2) Expression [ Time Frame: Biopsy/Week 1 and Surgical Resection/Week 2 ]
    Mean percentage of cells expressing human epidermal growth factor receptor 2 (Her2)
tumor characteristics, proliferation and apoptosis, ER, PR, HER2 expression [ Time Frame: biopsy and surgical resection ]
Complete list of historical versions of study NCT00612560 on Archive Site
Growth Hormone Serum Levels IGF-1 [ Time Frame: Biopsy/Week 1 and Surgical Resection/Week 2 ]
Mean serum level IGF-1(pg/ml)
steroid and growth hormone serum levels [ Time Frame: biopsy and surgical resection ]
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Flaxseed, Aromatase Inhibitors and Breast Tumor Characteristics
Flaxseed vs. Aromatase Inhibitors: Breast Tumor Characteristics and Prognosis
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.
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.
Not Applicable
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Breast Cancer
  • Drug: Anastrozole
    1 mg per day
    Other Name: Arimidex
  • Dietary Supplement: flaxseed
    25 g per day ground
  • Drug: Placebo
    Placebo pill 1 per day
  • Experimental: 2
    Flaxseed 25 mg per day and 1 placebo pill per day
    Intervention: Dietary Supplement: flaxseed
  • Experimental: 3
    25 mg flaxseed per day and 1 mg anastrozole pill per day
    • Drug: Anastrozole
    • Dietary Supplement: flaxseed
  • Placebo Comparator: 4
    Placebo pill 1 per day
    Intervention: Drug: Placebo
  • Experimental: 1
    Anastrozole 1 mg pill per day
    Intervention: Drug: Anastrozole
McCann SE, Edge SB, Hicks DG, Thompson LU, Morrison CD, Fetterly G, Andrews C, Clark K, Wilton J, Kulkarni S. A pilot study comparing the effect of flaxseed, aromatase inhibitor, and the combination on breast tumor biomarkers. Nutr Cancer. 2014;66(4):566-75. doi: 10.1080/01635581.2014.894097. Epub 2014 Mar 26.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
April 2014
January 2011   (Final data collection date for primary outcome measure)

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 years
  • 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 antibiotics
  • 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
Sexes Eligible for Study: Female
18 Years to 85 Years   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
I 99507
R21AT004024-01 ( U.S. NIH Grant/Contract )
Not Provided
Not Provided
Roswell Park Cancer Institute
Roswell Park Cancer Institute
  • National Center for Complementary and Integrative Health (NCCIH)
  • AstraZeneca
Principal Investigator: Tracey L O'Connor, MD Roswell Park Cancer Institute
Roswell Park Cancer Institute
September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP