Southern Illinois University Nutri-Flax study
FLAX LIGNANS HAVE ANTICANCER
EFFECTS IN BREAST TISSUE By Dr. Diane H. Morris
Large-scale population studies show that diets rich in lignans are associated with a reduced risk of breast cancer. Flax and its lignans help protect against breast cancer by altering the metabolism of estrogen and by decreasing cell proliferation, according to findings from a small number of clinical studies. The animal data are strong - flax and its main lignans interfere with cancer processes and inhibit metastasis of mammary (breast) tumours to the lungs and other organs. One animal study found that the combination of flax and tamoxifen alone. Eating flax regularly may reduce breast cancer risk and improve the clinical prognosis for women with breast cancer.
Whole flax seeds and milled flax are excellent sources of lignans. Indeed, flax is the riches known dietary source of lignans. Lignans are phytoestrogens - plant compounds that can affect estrogen metabolism in animals and humans. The main flax lignan is secoisolariciresinol diglucoside (SDG). SDG is converted to the enterolignans or mammalian lignans - namely, enterodiol and enterolactone - by the action of bacteria in the colon. Human and animal studies support a role for flax and its lignans in breast cancer prevention and control.
Information about flax lignans, their roles as phytoestrogens and antioxidants , and their anticancer effects can be found in Chapter 4 and 6 of the Council’s book, Flax-A Health and Nutrition Primer, which is available on-line at
Flax Helps Protect Against Breast Cancer by Influencing Estrogen Metabolism
Breast cancer is hormone-sensitive, meaning that in the early stages, tumour growth is influenced by the sex hormones, particularly estrogen and its metabolites. The biologically active form of estrogen is estradiol, which is oxidized mainly in the liver to estrone. Estrone can be converted to two metabolites with different biologic effects - 2-hydroxyestrone has little biologic activity, while 16α-Hydroxyestrone enhances estrogen activity and promotes uncontrollable tumour cell growth or cell proliferation, as it is called. Women who produce more 16α-Hydroxyestrone may have an increased risk of breast cancer. Two clinical studies found that postmenopausal women who ate a diet supplemented with 10 g or 25 g of milled flax for 7 weeks or 16 weeks increased the excretion of 2-hydroxyestrone in their urine, without increasing the excretion of 16α-Hydroxyestrone. In these studies, flax consumption shifted the balance toward production of the relatively inactive metabolite of estrogen, thus suppoeting a role for flax seed in breast cancer prevention.
Estrogen Receptors In Breast Tumours
Breast tumours that contain receptors for estrogen are estrogen receptor positive (ER+); tumours that lack estrogen receptors are called ER negative (ER-). Women with ER+ tumours are more likely to respond to hormone therapy than women whose tumours are ER-.
Population Studies Suggest a Protective Effect of Dietary Lignans
According to two recent reviews of large-scale population studies published since 1997, plant and mammalian lignans appear to protect against breast cancer, at least in premenopausal women. The cancer protective effects of lignans in this population may be determined by the type of estrogen receptor in women’s breast tissue.
One protective cohort study among 58,049 postmenopausal French women found that those with the highest dietary lignan intake (>1395 µg per day) had a significantly reduced risk of breast cancer. The beneficial effect of dietary lignans in this study was limited to ER+ and progesterone-positive breast cancers, suggesting a strong role for hormone receptors in controlling the biologic effects of lignans.
Flax Interferes with Cancer Processes in Animal Studies
Flax fed to carcinogen-treated rats and mice reduced tumour incidence, number, and size at the initiation, promotion and progression stages of mammary (breast) cancer. Milled flax fed to rats decreased tumour incidence, number and size and resulted in lower levels of cell proliferation in mammary tissue. Feeding milled flax slowed tumour growth rate in mice implanted with an ER- human breast cancer cell line and decreased tumour weight and volume in mice implanted with ER+ human breast cancel cell line.
Feeding pure SDG to rats appears to inhibit mammary tumour growth at the early promotion stage of cancer development. Thus, pure SDG may affect new tumour development, whereas milled flax appears to exert its effects at later stages of tomour growth.
Flax Enhances Tamoxifen’s Anticancer Effects in Mice
Tamoxifen is widely used as adjuvant therapy for breast cancer, especially in women who have ER+ breast cancer. Despite its proven anticancer effect, tamoxifen has troubling side effects. A question often asked by women with breast cancer is this: Do flax lignans interfere with or enhance the anticancer actions of tamoxifen?
A mouse study was conducted at the University of Toronto to answer this question. The study assessed the effect of flax and tamoxifen, alone and in combination, on the growth of ER+ human breast cancer cells in mice.
Nude mice were injected with estrogen-dependent MCF-7 cells and then fed one of several diets. The diets contained 10% milled flax, a tamoxifen pellet (5 mg), or both. (A 10% flax diet is strongly equal to a human diet containing about 20-25 g or 2-3 tbsp of milled flax daily.) Tumour growth was monitored weekly.
In these mice, dietary flax inhibited the growth of human ER+ breast cancer cells. At low 17β-estradiol levels, flax regressed tumour size by 74%; at high 17β-estradiol levels, flax regresses tumour size by 22%. (17β-estradiol is a key human estrogen.) Furthermore, flax enhanced the anticancer effect of tamoxifen - that is, flax + tamoxifen achieved a tumour regression >53% compared with tamoxifen alone.
Mechanism of Lignans’ Anticancer Effects
Mammalian lignans appear to exert anticancer effects through both hormone and non-hormone-related actions. The mammalian lignans enterodiol and enterolactone inhibit two key enzymes involved in estrogen synthesis; both enzymes are associated with increased breast cancer risk. Mammalian lignans may also have non-hormone-related actions, such as antioxidant activity, inhibiting angiogenesis and cell proliferation, and/or altering the expression of growth factors that stimulate tumour development.
More Clinical Studies of Flax and Cancer Are Needed
The findings of animals studies strongly suggest that flax and its lignans have anticancer effects. Although the clinical findings are promising, more clinical work is needed to confirm the anticancer effects of flax and the flax intake needed to achieve breast cancer protection.
Research May Help Determine if Flaxseed Benefits
Women with Ovarian Cancer
Why is this study being done?
The goal of this study is to determine if women who have been diagnosed with ovarian cancer, and are currently in remission, can tolerate 20g per day (approximately 3 tablespoons) of ground flaxseed as a dietary supplement. Flaxseeds contain a good amount of fiber, phytoestrogens (lignans) and omega-3 fatty acids (fats that are found in plant or fish products). Lignans and omega-3 fatty acids have been widely studied and are known for various health benefits, including reducing the risk of cardiovascular disease and inflammation. Investigators from our institution have completed studies that suggest flaxseed can slow the growth of ovarian cancer in hens (an appropriate animal model for human ovarian cancer). Thus, they believe that dietary supplementation with flaxseed could help prolong the disease-free interval and possibly prevent recurrence of ovarian cancer. The addition of flaxseed to a healthy diet is currently being investigated in numerous clinical trials; however, this will be the first study to examine the effects of flaxseed supplementation in women who have been diagnosed with ovarian cancer.
Who is eligible for this study?
- Patients age ≥ 21 years
- Patients with a diagnosis of ovarian cancer including epithelial ovarian carcinoma, primary peritoneal cancer or fallopian tube cancer who are currently in clinical remission as determined by their gynecologist/oncologist
- Those at risk of clinical relapse: patients of any stage who are in remission from ovarian cancer who have previously undergone surgical debulking and adjuvant chemotherapy
- Eligible patients must have adequate bone marrow function, renal function and hepatic function
What will happen if you take part in this research study?
Before you begin the study...
- Your gynecologic oncology physician will perform a physical exam and a review of your level of activity and your blood test results to ensure that you are in remission. This will be done as a part of your routine care during your post-chemotherapy visit.
During the study...
- You will be required to consume 20g (approximately 3 tablespoons) of ground flaxseed per day for two years (24 months), Sealed individual packets will be provided to you.
- You will be required to record your daily flaxseed and fluid intake on a monthly dietary log.
- You will return to the SIU Gynecologic Oncology office every 3 months (as part of your standard treatment and surveillance) to see your physician, you will return any unused portion of your flaxseed supply and review your dietary and fluid logs.
- You will be asked to donate a urine sample and an additional tube of blood for research at each of your follow-up visits (every 3 months) for two years after the initiation of the study.
- You will be required to complete a survey regarding your physical, social, emotional and functional well-being. being. You will repeat the same survey after one year of flaxseed supplementation and then again at your last visit.
For more information go to: clinicaltrials.gov, search for: NCT02324439
Please feel free to contact our study team with any questions:
Kathleen Groesch, MS, CCRP
Paula Diaz-Sylvester, PhD
Laurent Brard, MD, PhD
Terri Wilson, BA