Green tea and breast density in at-risk postmenopausal women

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

Relation

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 Breast Cancer Risk.Cancer Prev Res (Phila). 2017;10(12):710-718.

Objective

Determining the Effect of 12 Months Daily Consumption of Green Tea Extract (GTE) on Mammographic Density (MD)

Draft

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

Participant

Healthy postmenopausal women (N = 1,075) aged 50 to 70 years at high risk of breast cancer due to “heterogeneously dense” or “extremely dense” breast tissue (>50% fibroglandular tissue) as defined by the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) Density Assessment Criteria.

Women were randomized to receive either the GTE intervention (n = 538) or placebo (n = 537). Of those assigned to the GTE intervention, 463 completed the study according to intention-to-treat (ITT) guidelines. Ultimately, 462 participants in the GTE group were analyzed (1 was excluded from analysis because mammography was not available at month 12). Of the 537 participants assigned to the placebo intervention, 474 completed the study according to ITT guidelines and 470 were analyzed (4 were excluded from analysis because mammography was not available at month 12).

Green tea has a good safety profile, a long historical use, a growing number of positive clinical studies, and is generally well tolerated. it may further prove to be a promising adjunct in breast cancer prevention.

Baseline characteristics of study participants (n=932) were evenly distributed between the GTE and placebo groups. The mean (SD) baseline age was 59.8 (±5.0) years. The mean (SD) BMI was 25.1 (±3.7). The majority of participants had some college education, were nonsmokers, and parous; The vast majority (97%) were non-Hispanic white women.

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

intervention

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

Study parameters assessed

Each participant had a mammogram at baseline (month 0) and month 12 to assess MD before and after the intervention. Comprehensive medical history questionnaires were completed at baseline, which included questions about lifestyle, demographics, medication and supplement use, and medical and reproductive history. Diet history questionnaires were completed at baseline and at the end of the intervention. Liver function and possible adverse events were closely monitored throughout the procedure. During the pre-intervention screening visitCOMEGenotyping was performed, 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 evaluated.

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

Primary outcome measures

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

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

Key insights

Overall, 12 months of daily GTE did not significantly reduce PMD or absolute mammographic density compared to placebo after adjustment for age (at baseline) and BMI (at baseline and month 12). However, in women aged 50 to 55 years 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 (Pfor difference = 0.05). A statistically borderline significant result (PInteraction = 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/food intake remained stable in both groups over the course of the 12-month study.

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 among all genders and accounting for 15.3% of all new cancer cases.²While nearly 90% of people diagnosed with breast cancer are still alive 5 years after diagnosis, an estimated 40,920 people in the United States will die from the disease in 2018. It is estimated that 12.4% of women in the United States will be diagnosed with breast cancer sometime in their lives, based on data from 2013-2015.²

Mammographic density reflects the relative ratio of fibroglandular tissue to adipose tissue in the breast and serves as an established predictor of breast cancer risk.^3.5Boyd, et al. reported that a 2% increase in breast cancer risk was associated with every 1% increase in MD.³In an intervention study, taking postmenopausal hormones was shown to increase MD by 4.7% after 12 months of use, potentially leading to a 9.4% increase in breast cancer risk.⁴

In contrast, the 4.4% decrease in MD observed in the present study in women aged 50 to 55 years who consumed GTE for one year could potentially result in an 8.8% reduction in breast cancer risk. Interestingly, Cuzick et al reported that tamoxifen (an estrogen receptor antagonist in breast tissue and first-line antiestrogen drug) had a similar effect, reducing breast density by 4.4% over 18 months compared to placebo (P<0.001).⁵In 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 aged 45 years or younger; Among those aged 55 and over, MD decreased by only 1.1% with the same intervention and time frame. Whether GTE supplementation in women aged 45 years or younger for 54 months would result in a similar reduction in MD compared to tamoxifen remains to be studied but is certainly of interest. Similarly, in women aged 55 or younger, would GTE supplementation beyond 1 year result in additional reductions in MD? We don't know yet, but the intriguing results of the GTE study warrant additional research into these questions.

A 2007 study published in theNew England Journal of Medicinefound that women with more 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), with the risk being particularly high for women younger than 56 years. In this group, MD of 50% or greater accounted for 26% of all breast cancer cases and 50% of cancers detected within 12 months of a negative screen.⁵Given the value of PMD in predicting a woman's risk of developing breast cancer, healthcare providers should consider interventions to reduce breast density when developing strategies to reduce breast cancer risk.

The study examined in this review has particular relevance to women aged 50 to 55 years 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 positive clinical studies, and is generally well tolerated. it may further prove to be a promising adjunct in breast cancer prevention. It would be great to see if further studies could replicate the results of this study. It would also be helpful to have a more ethnically and racially diverse population in future studies so that results are generalizable to and reflective of our diverse population.