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

4.3. Omega 3 Polyunsaturated Fatty Acids (PUFA)

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are long-chain (-3) polyunsaturated and highly peroxidizable fatty acids which are obtained mainly from marine sources. These supplements have important anti-inflammatory properties. Based on the results of preclinical and clinical studies, supplementation with omega 3 PUFA seems to be a promising approach among breast cancer patients. Food sources may be used with similar results [228]. Due to their nature, safety should not be a critical issue.

In a long-term prospective study, Brasky et al. showed an inverse association between the supplementation with omega-3 fatty acid and breast cancer risk [235]. This association depends on the type of fatty acids. For example, Pouchieu and colleagues [229] proved that specific plasma saturated, monounsaturated, and polyunsaturated fatty acids were differently associated with breast cancer risk. These authors reported that the total PUFAs were correlated with breast cancer risk only in the placebo group. Additionally, a modulation role of antioxidant agents in these associations via neutralizing the potential effects of these fatty acids on carcinogenesis was also suggested.

Different meta-analysis of epidemiological studies suggested that fish consumption and dietary fatty acids might be not associated with breast cancer risk [231–234]. Some authors proposed conducting well-designed prospective studies to explore the role of fish consumption/dietary fatty acids in relation to breast cancer risk [233]. However, Zheng et al. found an inverse relationship between dietary marine -3 PUFA and breast cancer risk. The increment of dietary -3 PUFA of 0,1 g/day may reduce breast cancer risk in 5% [238]. So, dietary oil fish intake or supplementation had a protective effect in breast cancer patients [236]. More pronounced preventive effects were found between omega 3 and postmenopausal women at risk [236, 237]. The populations who consume high levels of omega 3 and low levels of omega 6 showed a breast cancer risk reduction. In contrast to omega 3, omega 6 induces inflammation reactions [241]. In a meta-analysis, Yang et al. also demonstrated the negative association between the higher omega 3: omega 6 ratio intake and breast cancer risk [239]. Similar results were achieved by Murff and collaborators [240].

The protective effect of omega-3 fatty acids was putted to the test in a pilot study of 35 postmenopausal women with cytological evidence of hyperplasia, with an intake of 1860 mg EPA + 1500 mg DHA ethyl esters daily for 6 months. A favourable decrease in several breast cancer biomarkers has indicated the need of further placebo-controlled clinical trials [243].

Patterson and collaborators did not associate EPA and DHA intake from fish oil supplements with breast cancer outcomes [230]. Sandhu et al. found an increased effect of protective omega-3 fatty acid supplementation in higher body mass index women [244].

To determine the dose of omega-3 fatty acids that reach the maximal target tissue effects in women at high risk of breast cancer, Yee et al. [242] suggested that doses up to 7.56 g of DHA and EPA (per day) were well tolerated with optimal compliance. A combination of omega 3 (4 g) and raloxifene (30 mg)—a breast cancer chemopreventive agent)—was successful in reduction insulin-like growth factor (IGF-1) levels and omega 3 added the additional effects of improving serum lipids, antioxidant, and anti-inflammatory activities [245, 246].

EPA and DHA can increase the production of ROS in cancer cells, so they are being investigated as promising adjuvants of cancer treatment (e.g., chemotherapy; radiotherapy) to maximize the sensitivity of residual tumour cells to the therapy and maintain or (preferably) decrease the sensitivity on nontumour cells without any additional side effects [383, 439]. A phase II trial has proved the safety and feasibility benefits of omega 3 PUFA when supplemented together with chemotherapy. Bougnoux et al. [247] supplemented with DHA (1.8 g/day) metastatic breast cancer patients that were receiving anthracycline-based chemotherapy. Despite the limited number of patients (i.e., ), the authors reported an increase disease-free survival and a longer time to progression in patients with high DHA incorporation into plasma phospholipids.

Considering the effects of EPA and DHA on cellular processes of bone turnover, these fatty oils may compensate aromatase inhibitors effects to bone and seems to be a promising approach in this clinical situation. Hutchins-Wiese et al. [248] supplemented postmenopausal breast cancer survivors with aromatase inhibitors with a high dose of DHA and EPA (4 g/daily for 3 months) and demonstrated that PUFA supplements can reduce bone resorption. Considering the short-term effects of fish oil supplementation, long-term studies are required.