New Evidence Suggests Chemoprevention Activity of Green Tea Supplements

Yu SS, Spicer DV, Hawes D, et al. Biological effects of green tea capsule supplementation in pre-surgery postmenopausal breast cancer patients. Front Oncol. 2013 Dec 13;3:298.

A presurgical trial comparing green tea capsule supplementation to no green tea supplementation

All of the study participants were postmenopausal female breast cancer patients who were at the Los Angeles County-University of Southern California Medical Center between 2008 and 2009. The green tea intervention group (n=13) included 12 patients with primary invasive stage I or II breast cancer and 1 with ductal carcinoma in situ (DCIS). The control group (n=15) included 10 patients with primary invasive stage I or II breast cancer and 5 with DCIS. All of the participants in the study were non–tea drinkers. ER/PR status was similar in both groups, with 4 in the treatment group who were ER-/PR- and 5 in the control group who were ER-/PR-.

The green tea capsule contained 725 mg of total green tea with 314 mg of epigallocatechin-3-gallate (EGCG). The daily dose was 3 capsules, so each participant received 940 mg of EGCG daily—the equivalent to about 8 to 10 cups of green tea. The intervention took place between breast cancer diagnosis and initial surgery date with an average duration of 35 days. This was not a placebo-controlled trial; the women in the control group did not take any capsules.

Urine samples measured tea catechin levels. Three key markers were measured in the diagnostic core biopsy tissue and surgical specimens:

Benign and malignant cells were separated. Samples were available from 13 breast cancer patients in the green tea intervention group and 15 controls.

In the green tea group, patients experienced a decrease in Ki-67 activity in benign cells (–3.14%; P=0.007), as well as malignant cells (–4.29%; P=0.10) compared to patients in the control group who experienced a statistically insignificant change in Ki-67 in the benign cell components (0.75%; P=0.22) and an increase in malignant cells (0.68%; P=0.91). The decrease in Ki-67 in benign cells in the green tea group reached statistical significance when compared to benign cells from the control group (P=0.033); however, changes in malignant cell components between the 2 groups did not reach statistical significance (P=0.45). The decrease in Ki-67 in the green tea group was found regardless of ER/PR status or tumor stage at diagnosis. There were no significant changes in casp-3 or CD-34.

The chemopreventive effects of green tea have been the subject of hundreds of studies. A 2008 review based upon 43 epidemiological studies, 4 randomized clinical trials, and one meta-analysis found that 58% of the included studies demonstrated a cancer prevention effect from long-term consumption of green tea.¹ A 2012 review of 8 cohort studies and 3 case-control studies by Sasazuki et al found a consistent small risk reduction of gastrointestinal cancers, especially in women who drank or took green tea.² In 2006, Bettuzzi et al studied men with high-grade prostatic intraepithelial neoplasia, a precancerous state, and found that men who took 200 mg green tea extract supplements for 1 year developed fewer cancers than men taking placebo.³ Of note, other studies have not shown benefit in prostate cancer prevention, including a small 2005 study involving men with hormone refractory prostate cancer.⁴ The anticancer effects of green tea in chronic lymphocytic leukemia were demonstrated in a 6-month phase 2 trial using 2000 mg of a green tea extract.⁵ In a pilot study of 136 patients, green tea supplementation equivalent to 10 cups of green tea daily (2.5 g green tea extract) reduced the incidence of colonic adenomas by 51% and was determined to be an effective chemopreventive agent for this precancerous condition of the colon.⁶

The chemopreventive properties of green tea specific to breast cancer have been demonstrated in at least 2 prospective clinical studies. The subjects in both studies were premenopausal women with diagnosed breast cancer who were followed after surgery for recurrence. In both studies green tea consumption greater than 5 cups per day was associated with a reduced risk of recurrence in women with stages I and II breast cancer. One study found a recurrence rate of 16.7% in women with stage I and II breast cancer who drank an average of 8 cups of green tea per day, compared to a recurrence rate of 24.3% in women drinking an average of 2 cups per day.⁷ The other study found a 57% decreased risk of recurrence in women diagnosed with stage I breast cancer who drank an average of 5 cups of green tea daily over 4.5 years.⁸ Prior studies have demonstrated a multifaceted impact of green tea on breast carcinogenesis. In 2012, data from Crew et al demonstrated that green tea supplementation prevented tumor cell growth, migration, and invasion in 34 women following breast cancer treatment.⁹ Because green tea extract has been shown to prevent or slow the growth of breast cancer cells, the National Cancer Institute is presently engaged in clinical trials to determine safety and dosage. One of the secondary outcomes measures of the phase I trials presently underway is to evaluate green tea’s ability to modulate immunohistochemical Ki-67 expression.¹⁰ This appears to be a key area of emphasis and potential.

 

The preventive effects of green tea have been related to its antiproliferative effects when studied in other cancer types. In 2009, Tsao et al saw partial regression (50%) in oral lesions compared to placebo, and the treatment group also experienced fewer increases in lesion size.¹¹ The dose used in that study was 3 g of mixed tea given orally and used topically. Tsao and colleagues noted that Ki-67 increased in the patients with oral cancer as the tissue went from normal to hyperplasia to dysplasia to cancer. While regression did not achieve statistical significance in this study, Tsao concluded that increased Ki-67 was associated with a higher risk of developing oral cancer and that impacting Ki-67 could decrease proliferation.

 

Proliferative potential is highly relevant with regards to breast carcinogenesis. High Ki-67 in residual disease after neoadjuvant therapy for breast cancer is associated with higher recurrence rates and worse disease-free survival.¹²

 

The findings of this clinical study indicated that green tea reduced cell proliferation in breast tissue. This has significant cancer prevention implications and underscores the importance of green tea in cancer prevention. The ability of green tea to effectively reverse established breast cancer has not been confirmed in published human clinical trials. Thus, its benefit appears to be most evident in women at risk for breast cancer or its recurrence.

 

On that note, in women receiving chemotherapy as a recurrence prevention strategy, there is question whether green tea will interfere with chemotherapy. Although a 2012 review by Sak concluded that catechins from green tea did actually increase the efficacy of some chemotherapeutic agents, such as doxorubicin, in drug-resistant tumors, the conclusion is based primarily on in vitro and in vivo data.¹³ Green tea has been shown to work synergistically with the taxanes (paclitaxel, docetaxel), as well as fluorouracil, floxuridine, and capcetibine.¹⁴ A 2007 animal study also showed that green tea polyphenols were protective against lipid peroxidation and inflammation induced by the chemotherapeutic drug irinotecan.¹⁵

 

The discussion of chemotherapy is beyond the scope of this commentary. The present study enhances our understanding of one of the mechanisms by which green tea can help prevent breast cancer development and its recurrence. The use of green tea as a key component of an integrative breast cancer prevention strategy makes clinical sense. This study suggests that for patients who are not consuming the recommended amount of green tea, taking a green tea supplement at a dosage of 940 mg EGCG daily is a viable alternative.