Phytotherapy and Nutritional Supplements on Breast Cancer 用于乳腺癌治疗的植物疗法和营养补充剂

3.6. Linum usitatissimum

Linum usitatissimum (flaxseed) is known for its phytoestrogen lignans content, namely, secoisolariciresinol diglucoside, which are converted into mammalian lignans (enterolactone and enterodiol) by bacterial fermentation in the colon [270]. This bacterial conversion beneficially influences the anticancer effects of flaxseed [271]. Based on their structural similarity to estrogens, mammalian lignan metabolites can attach to oestrogen receptors and inhibit the growth of estrogen-stimulated breast cancer [3]. Flaxseed can modulate the estrogen metabolism and oestrogen receptor and epidermal growth factor receptor signalling pathways [272]. Flaxseed also contains up to 40% oil which is mainly rich in α-linolenic acid-rich oil (i.e., -3 polyunsaturated fatty acid).

However, some questions remain and are discussed, such as if flaxseed and its compounds are effective in reducing the breast cancer risk, present antiproliferative properties, and can interact beneficially with conventional cancer therapy.

In 2013, a Canadian study revealed that flaxseed intake alone is associated with a prevention of breast cancer [59].

In vitro studies showed that flaxseed induces apoptosis and inhibits human breast cancer cells proliferation [273–276]. Animal models have shown that flaxseed, secoisolariciresinol diglucoside, and flaxseed oil can reduce the growth of breast cancer [277–279]. Additionally, experimental studies using rodents demonstrated that flaxseed dietary inclusion has antiproliferative effect in different heterotransplanted mammary carcinomas in mice [280–282]. For example, Chen et al. proved that flaxseed diet on a mouse model has a dose-dependent inhibition of breast tumour growth [283]. In addition, flaxseed also contributed to decreased metastasis and tumour angiogenesis [60, 279, 284].

Even though numerous experimental studies using animal models being available in literature, there are a few studies concerning the influence of flaxseed on breast carcinomas in humans and more clinical trials are required to assess whether flaxseed has anticancer properties in humans. No study reveals that flaxseed has a negative effect. For example, in a double-blinded, randomized controlled clinical trial, the dietary flaxseed demonstrated remarkable protection with a reduction in tumour growth and alteration of tumour biological markers in postmenopausal breast cancer patients [285]. Buck and collaborators [63, 286] also reported the beneficial effect of flaxseed ingestion and high serum lignan levels in the survival rate of postmenopausal patients with breast cancer.

Taking into consideration the interaction of flaxseed in chemotherapy, Chen et al. demonstrated that -3 fatty acid-rich cotyledon fraction of flaxseed reduced the growth of ER-positive human breast tumours, alone and in combination with tamoxifen, increasing the effectiveness of this chemotherapeutic agent [280]. Some studies reported the decreased tumour angiogenesis with the association of flaxseed and tamoxifen [60, 61] and the tumour cell apoptosis with flaxseed and doxorubicin [287]. In a recent study, Manson et al. reported that dietary flaxseed presented minimal tumour-reducing outcome did not interfere with trastuzumab action (a recombinant humanized monoclonal antibody used as the first-line therapy in HER2-overexpression breast cancer) but enhanced survival in athymic mice with established HER2-overexpressing human breast tumours [288]. However, the use of flaxseed oil combined with trastuzumab increased the effectiveness of low doses of this monoclonal antibody, that is, reduced tumour size and cell proliferation and increased apoptosis on HER2-overexpressing breast tumours (BT-474) in athymic mice compared to trastuzumab alone [289]. The author suggests the potential use of flaxseed oil as a complementary treatment for premenopausal women undergoing trastuzumab treatment, reducing the dose, and, therefore, lowering the side effects and potentially increasing survival rates. However, these recommendations should be confirmed through clinical trials. The use of flaxseed and aromatase inhibitor (using anastrozole as model drug) was also studied by MaCann and collaborators using biopsy and resection samples from postmenopausal women with oestrogen receptor-positive breast cancer [62]. Nevertheless, the results did not support strong effects on aromatase inhibitor activity but suggested that anastrozole might reduce the beneficial effects of flaxseed.

Additionally, Chen et al. verified that flaxseed components (secoisolariciresinol diglucoside and oil) did not attenuate the positive effects on bone health induced by tamoxifen (i.e., increase bone mineral content and density) in breast cancer patients [290].

Based on the current evidence, the flaxseed and its components are safe and effective in reduction risk and treatment of breast cancer. Despite this, the use of flaxseed is associated with bowel obstruction and bleeding disorder [3].