Lignans are phenolic compounds found frequently in fiber-rich plants, such as flax (Linum usitatissimum). Flax is particularly high in the lignans secoisolariciresinol diglucoside (SDG), SECO, and matairesinol. SDG is converted in the human colon by bacteria into the mammalian lignans enterodiol and enterolactone. Flaxseed, its lignans, and enterolactone have been studied for anticancer activity in vitro, in animal models, and among humans.1
Epidemiologic studies have evaluated both serum lignan concentrations and dietary intake for an association with cancer risk for several solid tumor types. Randomized controlled trials have evaluated the effect of dietary flaxseed on tumor tissue markers, with promising results.
A randomized controlled trial of cancer prevention or treatment has not, however, yet been conducted.
Several epidemiologic studies evaluated serum concentrations of enterolactone and breast cancer risk and prognosis. A study of 1250 postmenopausal breast cancer cases and 2164 from a population-based study demonstrated that high levels of serum enterolactone were significantly associated with a reduced risk of breast cancer (odds ratio [OR], 0.65; 95% CI, 0.52-0.83; P-trend = <.0001).2 This association was evident for hormone receptor–positive disease, but was greatest with hormone receptor–negative disease. HER2 expression did not affect the associations.
A prospective cohort study of 2182 patients aged 50 to 74 years at breast cancer diagnosis demonstrated that high enterolactone concentrations were significantly associated with decreased all-cause mortality (hazard ratio [HR], 0.94; 95% CI, 0.90-0.98), breast cancer–specific mortality (HR, 0.94; 95% CI, 0.89-0.99), and distant disease–free survival (HR, 0.94; 95% CI, 0.90-0.98) among women with stage 0 to IIIA disease.3
Using another approach, a study of 2999 breast cancer cases and 3370 healthy controls demonstrated that breast cancer risk was significantly reduced by dietary consumption of flaxseed (OR, 0.82; 95% CI, 0.69-0.97) and flax bread (OR, 0.77; 95% CI, 0.67-0.89).4
Dietary flaxseed may also have an effect on tumors. Tumor tissue was assessed from a trial that randomly assigned patients with newly diagnosed breast cancer to receive a muffin containing 25 g of flaxseed or placebo at the time of diagnosis and then at the time of definitive surgery. Urine samples and dietary questionnaires were also collected.5 The flaxseed arm demonstrated a significant reduction in markers of tumor growth including Ki-67 labelling index (34.2%; P = .001), c-ERBB2 expression (71%; P = .003), and an increase in apoptosis (30.7%; P = .007). Mean urinary lignan excretion was also increased in the flaxseed group compared with the placebo group.
Another study conducted among postmenopausal women receiving aromatase inhibitors demonstrated that flaxseed consumption trended toward a reduction in estrogen receptor (ER) beta expression by 40%, but these findings were not significant.6 Urinary enterolactone excretion was lower among patients receiving flaxseed plus an aromatase inhibitor compared with flaxseed alone, suggesting that aromatase inhibition may somehow affect enterolactone concentrations.