Green Tea and Reduction of Breast Cancer Risk: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Green Tea and Reduction of Breast Cancer Risk (NCT00917735), a randomized phase 2 study. The primary outcome is Mammographic Density.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group phase II trial comparing green tea extract with placebo. The registry lists enrollment of 1075 participants and identifies the study as completed. Its recorded dates are a start in 2009-07 and primary completion in 2014-06. The sponsor was the University of Minnesota.

The official title describes the trial as randomized, double-blind, and placebo-controlled; the registry classifies masking as quadruple. These labels describe the stated design but do not supply details about who was masked, how assignment was generated, whether allocation was concealed, or how masking was assessed. Those procedural details are not reported in the registry record.

The active product was green tea extract capsules containing 80.7 % total catechins, including 51.7 % EGCG. The placebo capsules contained 50% maltodextrin, 49.5 % cellulose, and 0.5 % magnesium stearate. The registry does not state the dose, dosing schedule, treatment duration, adherence criteria, or procedures for handling treatment interruptions.

The purpose was to study the effect of the supplement on breast cancer risk biomarkers in postmenopausal women with high breast density, including whether effects differed by COMT genotype. The listed primary outcome was mammographic density at baseline and month 12; other biomarkers named in the study summary include IGF-1, IGFBP-3, sex hormones, urinary estrogen metabolites, and plasma F2-isoprostanes. The registry record does not describe the planned model, covariate adjustment, genotype subgroup analysis, or sample-size justification.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Prior to randomization, participants went through a screening clinic visit in which anthropometric characteristics and blood pressure were measured. In addition, blood was drawn to assess catechol-O-methyltransferase (COMT) genotype, hepatic function, and serological markers of hepatitis B and C virus.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Mammographic density at baseline and month 12

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Mammographic Density, measured over Baseline and month 12.

The primary outcome was percent mammographic density, measured from digital images using a computer-assisted quantitative method. It was assessed at baseline and month 12. Mammographic density represents the proportion of the breast image occupied by dense tissue; the record describes the measured quantity as a percent. The registry reports the outcome parameter as a geometric mean with a 95% confidence interval.

Density was used as a biomarker of breast cancer risk rather than as a direct count of breast cancer diagnoses. Biomarkers can be useful in a trial when the question concerns a biological response over the study period, but a change in a biomarker is not itself proof of a change in later cancer incidence. The study summary also names other biomarkers, including IGF-1, IGFBP-3, estrone, estradiol, androstenedione, sex hormone binding globulin, urinary estrogen metabolites, and plasma F2-isoprostanes.

The registry record does not report the baseline or month 12 mammographic-density estimates, confidence intervals, or a between-group effect estimate. It also does not report a result by COMT genotype. Thus, the endpoint and measurement approach are described, but the posted results do not allow the magnitude, direction, or precision of the primary comparison to be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on distinguishing the outcome definition, the estimated effect, and the uncertainty around that estimate. The registry defines the primary outcome as percent mammographic density measured on digital images at baseline and month 12. It identifies a geometric mean and a 95% confidence interval as the reported summary form. However, it does not post the corresponding estimates or a between-arm comparison, so those statistical quantities cannot be interpreted for this trial.

What does a geometric mean describe?

General statistical explanation: a geometric mean summarizes values on a multiplicative scale and is often used when positive measurements are skewed or when relative changes are the principal interest. It is distinct from the arithmetic mean, which summarizes values on an additive scale. A geometric mean alone does not describe the spread of individual observations. The registry’s stated use of a geometric mean does not reveal the transformation, model, handling of zero values, or calculation details; these are not reported in the registry record.

General statistical explanation: a confidence interval conveys uncertainty in an estimate under the assumptions of the analysis. Its width reflects both the variability in the data and the amount of information available. An interval can be compatible with a range of possible effects; it does not directly state the probability that a particular effect is true. Although the endpoint entry names a 95% confidence interval, no interval limits are posted for mammographic density. The degree of precision is therefore unknown.

What would a between-group estimate add?

General statistical explanation: a treatment comparison is more informative than separate summaries for each arm because it directly addresses the contrast of interest. The comparison can be expressed on an additive or multiplicative scale, depending on the outcome and analysis. Its interpretation relies on knowing which time point or change measure was analyzed, the direction of the contrast, and whether adjustment was used. The registry lists baseline and month 12 but does not state whether the intended primary analysis compared month 12 values, changes from baseline, or another summary. It also does not provide an effect estimate.

The record’s primary outcome notation says that several categories or time points were not reduced to one comparison. When an outcome has multiple measurements, an analysis must specify which contrast is primary and how the remaining measurements are treated. Otherwise, a reader cannot identify the single estimate that answers the primary question. The details of the categories, their analysis, and the reason no single comparison appears are not reported in the registry record.

Why can multiple outcomes matter?

General statistical explanation: testing several endpoints, time points, or subgroups creates multiple opportunities to observe an apparently notable result by chance. A prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory analyses can help readers interpret a collection of tests. The registry lists three outcome measures, but it does not report a multiplicity strategy, a testing hierarchy, or which analyses were considered confirmatory. The record does not report p-values or estimates for those outcomes.

How should genotype claims be assessed?

The trial summary states a hypothesis about women with the low-activity COMT genotype. General statistical explanation: evidence that an effect differs by genotype is usually assessed by directly comparing treatment effects across genotype groups, often through an interaction analysis. Finding an effect in one subgroup and not another does not, by itself, demonstrate that the subgroup effects differ. For a reliable reading, the subgroup definitions, numbers analyzed, estimates, confidence intervals, and interaction result are relevant. None of those results is reported in the registry record.

What do the planning assumptions mean?

The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. The specific planning outputs are not included in the registry record discussed by the outcome entry, and the primary effect itself is not posted. Such illustrations are not observed power and should not be read as evidence that the trial had a particular probability of detecting its actual effect. They are conditional on planning assumptions, including the effect size chosen for the illustration.

The record does not report the trial’s own sample-size justification, target effect, assumed variability, allowance for attrition, or whether any interim analyses were planned. These details cannot be inferred from the enrollment figure or from a planning illustration. Enrollment describes how many participants entered the study; it does not disclose how the original design was justified.

Finally, a complete statistical interpretation would need the analysis population, missing-data handling, model specification, protocol deviations, and outcome estimates. These items are not reported in the registry record. Their absence limits assessment of how closely the analysis followed the intended design and how sensitive the results might be to missing observations or analysis choices.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, but it does not report a multiplicity plan. The primary outcome entry also notes that several categories or time points were not reduced to one comparison. Without a stated hierarchy, adjustment method, or clear distinction between primary and exploratory analyses, it is not possible to determine how the family of outcome tests was intended to be interpreted. No outcome estimates or p-values are posted to show which comparisons were conducted or what they found.

General statistical explanation: when several outcomes, time points, or subgroup comparisons are examined, the chance of at least one apparently notable finding can increase. Multiplicity methods can address that issue, while a prespecified primary contrast can make the main inferential question clearer. The record does not report whether such methods were used, and their use should not be assumed.

Missing-data handling is not reported in the registry record. There is no description of how unavailable month 12 measurements, withdrawals, or other incomplete records were handled, nor whether sensitivity analyses were performed. The analysis population is also not reported: the record does not specify whether the outcome analysis used all randomized participants, participants with observed measurements, or another defined group. The distinction matters because exclusions after randomization can affect how well the comparison preserves the original randomized groups.

The registry’s stated enrollment is 1075, but that number alone does not establish how many participants contributed to the primary endpoint analysis. Arm-specific endpoint denominators, reasons for missing measurements, and any imputation or weighting procedures are not reported. Thus, neither the extent nor the potential impact of missing outcome data can be assessed from the posted record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: elevated alt or ast enzyme (1.3%), surgery (0.6%), diagnosis of uterine cancer (0.4%), motorcycle accident (0.2%), hypertension (0.2%).

The registry lists serious adverse events for 538 participants at risk in the green tea extract arm and 537 at risk in the sugar pill arm. It records 12 serious-event-affected participants in the green tea extract arm and 8 in the sugar pill arm. These are posted counts, not a treatment-effect estimate. The registry does not provide a statistical comparison or confidence interval for the serious-event counts.

The listed serious-event terms and percentages are Elevated ALT or AST enzyme, 1.3%; Surgery, 0.6%; Diagnosis of Uterine Cancer, 0.4%; Motorcycle accident, 0.2%; Hypertension, 0.2%; and Diarrhea, 0.2%. The record does not provide arm-specific counts for each term in this list, so the percentages should not be interpreted as a direct comparison between arms. It also does not report event timing, attribution to treatment, or further clinical detail for these terms.

The adverse-event entry separately records other affected counts of 407 for green tea extract and 391 for sugar pill, with the same arm-specific at-risk counts. The registry record does not define these other-event fields in enough detail to establish what events or participants they include. Death counts are listed as null, which means death information is not reported in the registry record; it should not be read as a reported count of zero.

12. What the Result Does, and Does Not, Mean

The record establishes that a randomized, placebo-controlled phase II trial of green tea extract was conducted in postmenopausal women with high breast density. Its primary endpoint was mammographic density at baseline and month 12, and its stated rationale included a possible difference by COMT genotype. The posted information describes the study question and selected design features, but it does not report the primary endpoint estimates.

Without the mammographic-density values, a between-group estimate, and its confidence interval, the direction and size of any observed effect are unknown. There is also no result to evaluate for precision or to compare with a clinically or scientifically meaningful threshold. The registry record does not report a result for the proposed low-activity COMT subgroup, so the genotype hypothesis cannot be judged from the posted results.

The study concerned biomarkers associated with breast cancer risk, not a reported comparison of breast cancer incidence as the primary endpoint. A biomarker finding, if one were reported, would need to be interpreted as evidence about that measure, not automatically as evidence of fewer or more cancer diagnoses. The record’s summary describes a preventive rationale, but no breast cancer prevention effect can be concluded from the available outcome information.

The safety entry provides serious-event counts and a list of selected serious-event terms, but it does not report a comparative safety analysis, event attribution, or uncertainty around the counts. These entries are useful descriptive information, but they do not resolve the missing primary outcome results.

Accordingly, the registry supports a description of the trial’s design, target population, intervention, comparator, endpoint, and selected adverse-event reporting. It does not support a conclusion about whether green tea extract changed mammographic density, whether any change varied by genotype, or whether the biomarker response translated into a change in breast cancer occurrence. Those results are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for separating a biological-risk question from a disease-outcome question. It focused on mammographic density and other biomarkers associated with breast cancer risk, while the study summary framed the research motivation in terms of prevention. That distinction matters because a biomarker endpoint and a clinical diagnosis answer different questions. Results for a biomarker would not, on their own, establish the effect on cancer occurrence.

The design also raised a genotype question: whether the response to green tea extract might be concentrated among women with the low-activity COMT genotype. Statistically, this requires more than comparing a treatment result within one genotype group with a result in another. A direct estimate of the difference in treatment effects, with appropriate uncertainty, is needed to evaluate effect modification. The registry record does not report such an analysis, so the proposed subgroup hypothesis remains unanswered in the posted results.

The endpoint was measured at baseline and month 12, yet the registry notes that multiple categories or time points were not reduced to a single comparison. This illustrates why a clear primary contrast matters. Specifying the principal time point, analysis scale, and comparison helps readers distinguish the central trial question from additional analyses. Those details and the endpoint results are not reported in the registry record.

Finally, the entry offers selected design and safety information but no posted primary analysis. This makes it a useful example of the difference between a completed trial record and an interpretable treatment-effect report. Enrollment, masking labels, and adverse-event counts do not substitute for an outcome estimate and its uncertainty. Statistical conclusions depend on those results and on sufficient information about the analysis that produced them.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting this trial is that the registry record does not report the primary mammographic-density results. No baseline or month 12 estimates, treatment contrast, confidence interval limits, or endpoint p-value are posted. As a result, the central efficacy question cannot be answered from the record, and the precision of any effect is unknown.

The entry states that the primary endpoint has several categories or time points and was not reduced to one comparison. It does not explain the categories, identify a primary contrast, or describe how repeated measurements were analyzed. The record lists three outcome measures but does not report the results or a multiplicity strategy. This limits assessment of which findings, if any, were treated as primary and how additional testing was handled.

The study summary identifies a proposed effect among women with the low-activity COMT genotype, but genotype-specific estimates and an interaction analysis are not reported in the registry record. The genotype group definitions, group sizes, and analysis plan are also not reported. The hypothesis therefore cannot be evaluated, and the registry does not establish whether the trial was designed or analyzed to provide a precise subgroup estimate.

Other design and analysis details are absent, including the randomization procedure, allocation concealment, treatment dose and schedule, adherence, analysis population, missing-data methods, model specification, and sample-size justification. The record does not report whether interim analyses were planned. These gaps prevent a fuller appraisal of conduct and statistical robustness. The serious adverse-event entry also lacks arm-specific details for the listed event terms, attribution, timing, and death counts; the death entries are null rather than reported values.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Green Tea and Reduction of Breast Cancer Risk — NCT00917735.
• Registry record last updated 2016-02-22; status last verified 2016-01.
• Results first posted 2016-02-22.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT00917735, titled Green Tea and Reduction of Breast Cancer Risk, is a completed phase II randomized parallel-group trial sponsored by the University of Minnesota. The registry records enrollment of 1075, a start in 2009-07, and primary completion in 2014-06. It compared green tea extract capsules with placebo in postmenopausal women described as having high breast density and being at high risk of breast cancer.

The primary outcome was percent mammographic density measured on digital images at baseline and month 12, with a geometric mean and 95% confidence interval specified as the summary. The registry record does not report the primary endpoint results, a treatment comparison, or a genotype-specific result. It lists serious adverse events affecting 12 participants in the green tea extract arm and 8 in the sugar pill arm; death counts are not reported in the registry record.