Key Findings:
High concentrations of plasma estrogen are associated with an increased risk of developing breast cancer. Anti-estrogenic therapies such as tamoxifen or aromatase (estrogen synthetase) inhibitors, decrease the incidence and the growth of invasive and noninvasive breast cancer but have adverse side effects. When flaxseed was fed to carcinogen- treated rats at the preinitiation or promotion stages of carcinogenesis, significant reductions in mammary tumor incidence and size were observed. When it was fed at a time when mammary tumors were already established, the mammary tumors regressed in size. Tumor growth and/or the incidence of metastases were also reduced by dietary flaxseed in athymic mice injected with human ER-positive (MCF-7) or ER-negative (MDA MB 435) breast cancer cells. In this study, flaxseed reduced the cell proliferation marker Ki-67 when given preoperatively to newly diagnosed postmenopausal breast cancer patients. It also decreased c-erbB2 expression and increased apoptosis.
ABSTRACT:
Purpose: Flaxseed, the richest source of mammalian lignan precursors, has previously been shown to reduce the growth of tumors in rats. This study examined, in a randomized double-blind placebo-controlled clinical trial, the effects of dietary flaxseed on tumor biological markers and urinary lignan excretion in postmenopausal patients with newly diagnosed breast cancer.
Experimental Design: Patients were randomized to daily intake of either a 25 g flaxseed containing muffin (n = 19) or a control (placebo) muffin (n = 13). At the time of diagnosis and again at definitive surgery, tumor tissue was analyzed for the rate of tumor cell proliferation (Ki-67 labeling index, primary end point), apoptosis, c-erbB2 expression, and estrogen and progesterone receptor levels. Twenty-four hour urine samples were analyzed for lignans, and 3-day diet records were evaluated for macronutrient and caloric intake. Mean treatment times were 39 and 32 days in the placebo and flaxseed groups, respectively. Results: Reductions in Ki-67 labeling index (34.2%; P = 0.001) and in c-erbB2 expression (71.0%; P = 0.003) and an increase in apoptosis (30.7%; P = 0.007) were observed in the flaxseed, but not in the placebo group. No significant differences in caloric and macronutrient intake were seen between groups and between pre- and posttreatment periods. A significant increase in mean urinary lignan excretion was observed in the flaxseed group (1,300%; P < 0.01) compared with placebo controls. The total intake of flaxseed was correlated with changes in c-erbB2 score (r = _0.373; P = 0.036) and apoptotic index (r = 0.495; P < 0.004). Conclusion: Dietary flaxseed has the potential to reduce tumor growth in patients with breast cancer.