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

3.8. Green Tea

Green tea extract is prepared from the steamed and dried leaves of Camellia sinensis and contains flavonoids, a large group of polyphenolic compounds with antioxidants properties [269]. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea and has been the focus of preclinical and clinical research on health beneficial effects [3]. However, the main mechanism by which green tea might help to prevent cancer has not been recognized.

In vitro and animal studies demonstrated that tea polyphenols can inhibit tumour cell proliferation and induce apoptosis [315, 316]. Additionally, tea catechins have revealed the ability to inhibit angiogenesis and tumour cell invasiveness as well as modulate the immune system function [317].

The chemopreventive potential of green tea contrasts with the consistent results from animal models. Evidence of green tea consumption on breast cancer prevention and development is not supported by epidemiologic studies and the role of green tea consumption in breast cancer remains unclear. The results of antiproliferative effect of green tea extracts or its polyphenols from human studies are inconsistent and depend on the type of cancer [318]. A systematic review and meta-analysis of prospective observational studies, 57 relevant articles, concluded that tea consumption has no significant effect on the risk of common malignancies including breast cancer [65]. A prospective cohort study performed in Japan found no association between green tea drinking and risk of breast cancer [66]. However, in a case-control study conducted by Zhang and colleagues in Southeast Chine between 2004 and 2005, despite the fact that the authors concluded that regular consumption of green tea can protect against breast cancer, they also suggested more research to closely examine the relationship between tea consumption and breast cancer risk [67].

In a follow-up study, despite prevention recurrence of stage I and II breast cancer being observed with an increase green tea intake, no improvements were confirmed in patients with stage III breast cancer. A potential prevention of green tea consumption in breast cancer recurrence in early-stage (I and II) cancer was also reported by Seely et al. [77].

In order to better evaluate the in vivo exposure to specific tea catechins, two studies incorporated prediagnostic biomarkers of green tea intake and metabolism on risk of breast cancer [68, 69]. In a prospective cohort in China, urinary tea catechins and their metabolites were measured in 353 cases and 701 controls and no association was found between urinary concentrations of biomarkers measured and risk of breast cancer [69]. Similar results were achieved in a prospective cohort Japanese study in which tea catechins biomarkers concentrations were measured in plasma [68]. In both studies, the detectable rates of some biomarkers were as low as 20–30%, which increased concern about the sensitivity of the assays, because ~50% of study participants reported drinking at least one cup of green tea daily. Crew et al. conducted a study using archived blood/urine from a phase IB randomized, placebo-controlled dose escalation trial of an oral green tea extract, polyphenon E (Poly E), in breast cancer patients [70]. The results suggested that the consumption of EGCG can have a preventive effect in breast cancer by influencing the growth factor signalling, angiogenesis, and lipid metabolism mechanisms.

In a cross-sectional study, including 3315 Asian women, daily green tea consumption demonstrated a significantly lower mammographic density percentage compared to nontea drinkers [319]. Mammographic density is a well-established breast cancer risk factor. The difference in mammographic density was observed mainly among postmenopausal women. The authors suggest that long-term exposure to green tea may act as a protective approach in breast cancer.

In addition, genetic factors may have an important role in the influence of green tea on breast cancer, namely, genetic polymorphism in angiotensin-converting enzyme gene and in the catechol-O-methyltransferase gene, probably due to the interindividual differences in the metabolism and elimination of tea polyphenols [71, 72]. In the specific case of catechol-O-methyltransferase gene, studies have inconsistent findings. Wu et al. [73] conducted a population-based case-control study in Asians in Los Angeles County and reported that consumption of green tea was associated with significant reduced risk of breast cancer in women carrying at least one copy of the low-activity catechol-O-methyltransferase allele relative to nondrinkers. In women carrying both high-activity catechol-O-methyltransferase alleles no association was found. In the Chinese population, the catechol-O-methyltransferase genotype did not present any modifying effect on the association between tea consumption and breast cancer risk.

Green tea has also demonstrated a promising role as adjuvant of chemo/radiotherapy due to both additive or synergistic effects and amelioration of cancer therapy side effects [320]. However, further clinical research is required to ascertain the effectiveness of these actions. EGCG can modify the pharmacokinetics of tamoxifen and induce chemosensitization in tamoxifen-resistant breast cancer cells [321]. In another study, the cotreatment of EGCG and tamoxifen increased apoptosis and reduced tumour growth in breast cancer cells using a murine model of breast carcinoma, enhancing the cytotoxicity of paclitaxel [322]. EGCG also has antiproliferation activity against estrogen-induced breast cancer cells (e.g., sunitinib) [323] and sensitives hormone responsive tumours to drugs that act in steroid receptors (e.g., tamoxifen) [321, 324]. Li et al. reported chemosensitization and synergistic anticancer effects with the coadministration of EGCG and histone deacetylase inhibitor trichostatin A in oestrogen receptor-negative breast cancer cells [325]. Zhang et al. conducted a clinical trial in breast cancer patients undergoing radiotherapy and supplemented with EGCG. The results showed that EGCG and its metabolites could potentiate the effects of radiotherapy [74]. Green tea also seems to protect the body against the harmful effects of radiation and chemotherapy [7, 320].

In the Minnesota Green Tea Trial, 1075 postmenopausal women at high risk of breast cancer due to dense breast tissue randomly consumed green tea extract (845 mg EGCG) or placebo, daily for one year. The safety of green tea was also tested. The main conclusion was that there were no statistically significant differences between groups in frequencies adverse events or serious adverse events, but EGCG consumption leads to a higher incidence of nausea, dermatologic events, and alanine aminotransferase elevation [75].

Lazzeroni et al. [76] studied the EGCG tissue distribution and evaluated its effect on cell proliferation in breast cancer patients. The consumption of 300 g of tea catechin extract phytosomes (equivalent to 44.9 mg of EGCG) increased the bioavailability of EGCG, which was detectable in breast tumour tissue and is associated with a decrease in the tumour circulating biomarker revealing antiproliferative effects on breast cancer tissue.

Based on the current data, large randomized intervention trials focusing on the efficacy of green tea polyphenols are required before a recommendation as preventive-cancer should be made.

No known contradictions are reported. Green tea has been consumed safely over thousands of years; recently a liver toxicity has been reported. However, this is probably related to the presence of contaminants in the plant.