CHAPTER ONE
INTRODUCTION
1.1  Background to the Study Breast cancer is the second leading cause of cancer death in female patients after lung cancer. Thus, much research is being conducted for its prevention and treatment, including the role of diet. Because of its unique composition, flaxseed (FS) has been studied for its effect on breast cancer. Flaxseed (FS; Linum usitatissimum) is an oilseed containing approximately 40% oil (FSO), more than half of which is the n-3 polyunsaturated fatty acids (PUFA), _-linolenic acid (ALA), the highest level of the dietary phytoestrogen lignan, secoisolariciresinol diglucoside (SDG) (~1%), and approximately 30% dietary fiber. Due to the elevated contents of ALA, FSO is considered to be an anti-inflammatory agent, while the lignan components have documented anti-oxidant and estrogenic/anti-estrogenic activities. Dietary fiber is generally recognized as having many beneficial effects, including modulation of the gut microbiota with the production of short-chain fatty acids (SCFA). We previously showed that FS consumption was associated with the reduction in breast cancer risk. In mice injected with breast tumor cells, 10% FS significantly decreased the tumor size and growth at a late stage of carcinogenesis. The 10% FS-induced inhibition of breast cancer growth and metastasis was related to the downregulation of insulin-like growth factor 1 and epidermal growth factor. The FS inhibitory effect on breast cancer was also attributed to both FSO and SDG components (Chen et al. 2013). Flaxseed is also one of the most important sources of the lignan precursor secoisolariciresinol (SECO), which occurs as secoisolariciresinol diglycoside (SDG) oligomers bound to hydroxymethylglutaric acid in the flax seed coat. It has also been suggested that SECO itself may act as a lignin in the body. Plant lignans as a group consist of phenolic compounds including enterolactone (ENL) and enterodiol (ED) (as well as others that are classified as phytoestrogens) alongside isoflavones, coumestanes, mycotoxins, and stilbenes. Although many foods contain lignans, flaxseed is unique in that it is the densest source of the lignan SDG, with between 60 and 300 mg lignans per 100 g serving. This diverse class of constituents is thought to possess varying degrees of both estrogenic and anti-estrogenic effects in vivo in conjunction with more direct antitumor effects. Through metabolism by intestinal microbes, plant lignans are converted into their active mammalian forms, ENL and ED. These metabolites appear to be responsible for some of the anticancer effects that have been attributed to lignans. The potential therapeutic effects of phytoestrogen-containing plants continue to be explored in the literature. These compounds may have particular benefit in hormone-dependent conditions such as menopausal hot flashes. However, for women with breast cancer, the decision to consume phytoestrogen- containing foods or supplements may be difficult, owing to concerns that these agents may be cancer promoting. The objectives of this systematic review are to assess the efficacy of flaxseed or its constituents, including flaxseed oil and flax lignans, in the management of hot flashes in women at risk of breast cancer incidence or recurrence and to determine the effect of this intervention on risk of breast cancer development, recurrence, or mortality (Thompson et al. 2011).