Green Tea and Breast Density in At-Risk Postmenopausal Women

An ounce of prevention?

By Zach Kadro, ND

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This article is part of the 2018 NMJ Oncology Special Issue. Download the full issue here.  

Reference

Samavat H, Ursin G, Emory TH, et al. A randomized controlled trial of green tea extract supplementation and mammographic density in postmenopausal women at increased risk of breast cancer. Cancer Prev Res (Phila). 2017;10(12):710-718.

Objective

To determine the effect of 12 months of daily green tea extract (GTE) consumption on mammographic density (MD)

Design

Phase II, randomized, double-blind, placebo-controlled trial

Participants

Healthy postmenopausal women (N=1,075) between the ages of 50 and 70 at high risk of breast cancer due to having “heterogeneously dense” or “extremely dense” breast tissues (>50% fibroglandular tissue) as defined by the American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS) density assessment criteria.

The women were randomized to receive either the GTE intervention (n=538) or placebo (n=537). Of those allocated to receive the GTE intervention, 463 completed the trial following Intention to Treat (ITT) guidelines. Ultimately 462 participants in the GTE group were analyzed (1 was excluded from analysis because no mammogram was available at month 12). Of the 537 participants allocated to receive the placebo intervention, 474 completed the trial following ITT guidelines and 470 were analyzed (4 were excluded from analysis because no mammogram was available at month 12).

Green tea has a good safety profile, a long historical use, a growing number of favorable clinical studies, and is generally well-tolerated; it may well continue to emerge as a promising adjunct in breast cancer prevention.

Study participants’ (n=932) baseline characteristics were equally distributed between the GTE and placebo groups. Mean (SD) baseline age was 59.8 (±5.0) years. Mean (SD) BMI was 25.1 (±3.7). The majority of participants had some level of college education, were never-smokers, and were parous; the vast majority (97%) were non-Hispanic white women.

Baseline energy, food, and nutrient levels were similar between treatment groups, although a higher intake of vitamin supplements was found among GTE participants compared to the placebo participants (P=0.038).

Intervention

Green tea extract (decaffeinated) in capsule form, with each capsule containing 328.8 mg total catechins, 210.7 mg epigallocatechin-3-gallate (EGCG), and less than 4 mg caffeine; participants consumed 4 capsules a day, for a total of approximately 1,315 mg total catechins, 843 mg EGCG, and less than 16 mg total caffeine (equivalent to 5 brewed 8-ounce cups of decaffeinated green tea) per day, for 12 months.

Study Parameters Assessed

Each participant had a mammogram at baseline (month 0) and month 12, to assess MD pre- and postintervention. Comprehensive health history questionnaires, which included questions about lifestyle, demographics, medication and supplement use, and medical and reproductive history, were completed at baseline. Dietary history questionnaires were completed at baseline and end of intervention. Hepatic function and potential adverse events were closely monitored throughout the intervention. During the preintervention screening visit, COMT genotyping was conducted, along with nonfasting blood tests, vital signs, and anthropometric measurements. Other breast cancer biomarkers, including plasma insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), estrone, estradiol, androstenedione, sex hormone–binding globulin (SHBG), urinary estrogen metabolites, and plasma F2-isoprostanes were also assessed.

Mammographic density is calculated by dividing the dense area of the breast, called the absolute density, by the total breast area. It is reported as a percentage and may be referred to as percent MD (PMD).

Primary Outcome Measures

Change in PMD from baseline at the end of the 12-month intervention.

This study was part of a larger study that, in addition to MD, also assessed as primary outcomes circulating concentrations of IGF-1, IGFBP-3, reproductive hormones (estrone, estradiol, androstenedione) and SHBG; and the effects of COMT genotype on GTE effects.1

Key Findings

Overall, 12 months of daily GTE consumption did not significantly reduce PMD or absolute mammographic density compared to placebo after adjustment for age (at baseline) and BMI (at baseline and at month 12). However, for women aged 50 to 55 at enrollment, 12 months of daily GTE supplementation significantly reduced PMD, resulting in a 4.40% decrease in PMD compared to those receiving placebo, who experienced a 1.02% increase in MD (P for difference=0.05). A statistically borderline significant result (P interaction=0.07) was observed in the interaction between age and GTE supplementation on PMD change. Other factors, including BMI, years since menopause, alcohol, parity, and tea-drinking status showed no modifying effect on PMD with GTE intake.

Those in the placebo group experienced a significant reduction in vitamin C intake compared to the GTE group (P=0.045), but weight, BMI, and energy/diet intake remained stable in both groups over the course of the 12-month trial.

Practice Implications

In 2018 an estimated 266,120 new cases of breast cancer will be diagnosed in the United States, making it the most commonly diagnosed cancer across genders and accounting for 15.3% of all new cancer cases.2 While almost 90% of those diagnosed with breast cancer are still alive 5 years after diagnosis, an estimated 40,920 people in the United States will die of the disease in 2018. It is estimated that 12.4% of US women will be diagnosed with breast cancer at some time in their lives, based on 2013-2015 data.2

Mammographic density reflects the relative proportion of fibroglandular tissue to fat tissue in the breast and serves as an established predictor of breast cancer risk.3,5 Boyd, et al reported that a 2% higher risk of breast cancer is associated with every 1% increase in MD.3 In one interventional study, postmenopausal hormone use was shown to increase MD by 4.7% after 12 months of use, which could potentially translate to a 9.4% increase in breast cancer risk.4

In contrast, the 4.4% decrease in MD in women aged 50 to 55 who consumed GTE for 1 year, observed in the present study, could potentially translate to an 8.8% reduction in breast cancer risk. Interestingly, Cuzick et al reported tamoxifen (an estrogen receptor antagonist in breast tissue and first-line antiestrogen drug) demonstrated a similar effect, reducing breast density by 4.4% over 18 months compared to placebo (P<0.001).5 In the same study, Cuzick et al reported that after 54 months of treatment, tamoxifen reduced MD by 13.4% (95% confidence interval [CI]: 8.6-18.1) in women age 45 or younger; those older than 55 had only a 1.1% decrease in MD with the same intervention and time frame. Whether or not GTE supplementation in women 45 years or younger for 54 months would result in similar reductions in MD compared to tamoxifen has yet to be studied, but it is certainly of interest. Similarly, would GTE supplementation beyond 1 year in women age 55 or younger result in additional reductions in MD? We do not know yet, but the intriguing findings of the GTE study warrant additional investigations into these questions.

A 2007 study published in the New England Journal of Medicine found that women with greater than 75% MD had an increased risk of breast cancer compared to women with less than 10% MD (odds ratio [OR]: 4.7; 95% CI: 3.0-7.4), and the risk was particularly greater for women younger than 56 years. In this group, 26% of all breast cancer cases and 50% of cancers detected within 12 months of a negative screening were attributable to an MD of 50% or more.5 Given the value of PMD in predicting a woman’s risk of developing breast cancer, healthcare providers should consider interventions to reduce breast density when they are developing strategies to reduce breast cancer risk.

The study examined in this review has particular relevance for women ages 50 to 55 who are at increased risk of breast cancer due to increased breast density. Green tea has a good safety profile, a long historical use, a growing number of favorable clinical studies, and is generally well-tolerated; it may well continue to emerge as a promising adjunct in breast cancer prevention. It would be great to see if additional studies could replicate the findings of this study. It would also be helpful to have a more ethnically and racially diverse population in future studies so results can be more generalizable to, and reflective of, our diverse population.

About the Author

Zach Kadro, ND, is naturopathic doctor at the Goshen Center for Cancer Care, where he is a second-year resident specializing in naturopathic integrative oncology. Kadro obtained a bachelor of general studies degree from the University of Michigan (Ann Arbor) prior to completing his doctor of naturopathic medicine degree at Bastyr University. In addition to seeing patients at the cancer center, Kadro is also involved in developing a comparative effectiveness research project examining the effect of naturopathic care in conjunction with standard of care on the incidence and severity of chemotherapy-induced peripheral neuropathy compared with standard of care alone.

References

  1. National Institutes of Health, US National Library of Medicine. Green tea and reduction of breast cancer risk. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT00917735. Updated February 22, 2016. Accessed September 13, 2018.
  2. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer stat facts: female breast cancer. https://seer.cancer.gov/statfacts/html/breast.html. Last modified July 24, 2018. Accessed September 13, 2018.
  3. Boyd NF, Lockwood GA, Martin LJ, et al. Mammographic densities and breast cancer risk. Breast Dis. 1998;10:113-126.
  4. Greendale GA, Reboussin BA, Slone S, Wasilauskas C, Pike MC, Ursin G. Postmenopausal hormone therapy and change in mammographic density. J Natl Cancer Inst. 2003;95:30-37.
  5. Boyd NF, Guo H, Martin LJ, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007;356:227-236.