Pre-Surgical Study: Effect of Metformin on Breast Cancer Proliferation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pre-Surgical Study: Effect of Metformin on Breast Cancer Proliferation (NCT00930579), a na phase 2 study. The primary outcome is Tumor Proliferation in Tumor Specimens.

2. Clinical Question

The study is framed as a pilot investigation of the biological effects of metformin in a pre-surgical setting. Its central measurement is a tumor-tissue marker rather than a reported clinical event or longer-term outcome. The registry describes the measure as an examination of changes in proliferation, with the mean and standard deviation specified as the outcome summary.

Because the study has one group, the question is about change observed among participants receiving metformin, not a difference between metformin and an untreated or alternative-treatment group. A before-and-after pattern can describe what happened over the measurement period, but it cannot by itself separate a treatment effect from other explanations for change. The registry record does not report a numerical estimate of that change or an inferential result. Accordingly, the size and precision of any observed change cannot be assessed from the registry record.

3. Trial Design

This is a completed phase II, single-group pre-surgical intervention study sponsored by Columbia University. It concerns women with newly diagnosed early invasive breast cancer and evaluates metformin in relation to tumor proliferation. The registry lists enrollment as 35 and describes metformin as the intervention. The study's stated purpose is to use a pilot pre-surgical model to evaluate the drug's biological effects.

The design has no parallel control arm: allocation is listed as not applicable, and the model is single group. Masking is listed as none. The arm description says women with newly diagnosed early invasive breast cancer receive metformin. These design features mean the recorded comparison is not a randomized, masked comparison between treatment groups. The registry itself flags that the arms are not a like-for-like control comparison; in this study, there is only the metformin group.

The primary outcome timeframe is baseline to up to 4 weeks. The outcome is described as a change in tumor proliferation measured in tumor specimens, so the design uses a pre-surgical measurement window. The registry does not report the specific schedule of specimen collection, the treatment dose or regimen, or details of how the timing of surgery related to individual measurements. Those details are not reported in the registry record.

The registry describes 33 evaluable metformin-treated participants as included in the primary analysis. It does not explain why the analysis population differs from the enrollment figure or state how evaluability was determined. The record lists one outcome measure and one analysis, but does not report a fuller statistical analysis plan, a sample-size justification, or details of any interim analyses. The planning assumptions elsewhere associated with sample-size illustrations are not a description of the study's own design; they do not turn this single-group study into a two-arm trial.

The study is marked completed. Its listed start date is 2009-10-16 and its primary completion date is 2012-05-10. The registry record does not report a separate control group, random assignment, or masking procedures.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Of the evaluable metformin-treated patients, 33 participants were included in the analysis.

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.

Population: Of the 35 patients enrolled, 33 completed the trial and were considered evaluable. Patients were evaluable if they had sufficient pre and post treatment tumor tissue for analysis, and demonstrated at least 75% compliance with metformin, as measured by weekly telephone interviews and pill counts.

6. Primary Endpoint

The registry lists the primary outcome as Tumor Proliferation in Tumor Specimens, measured over Baseline, up to 4 weeks.

The primary endpoint is tumor proliferation in tumor specimens, expressed as the percentage of Ki-67-positive cells. The registry says the measure examines changes in proliferation through the amount of Ki-67 protein in the tumor. Measurements are specified from baseline to up to 4 weeks, during the pre-surgical intervention period. The endpoint is summarized as a mean with a standard deviation, and the analysis population is described as 33 evaluable metformin-treated participants.

As a general statistical and biological explanation, a tissue marker can provide a way to quantify a biological characteristic in the sampled tumor. A percentage-based measure expresses the share of cells in the specimen that meet the marker definition, while the mean describes the average value across the analyzed participants and the standard deviation describes variation among their measurements. Those summaries answer different questions: the mean describes the central value, and the standard deviation describes how spread out individual values are around it.

For an endpoint intended to reflect change, baseline and follow-up values need to be interpreted in relation to one another. The registry's description does not give the actual mean values, the estimated change, a standard deviation for change, or a confidence interval. It also does not specify whether the analysis used paired measurements, an adjusted model, or another method. The numerical size and precision of the outcome therefore are not reported in the registry record.

This marker endpoint is not, by itself, a report of a clinical outcome over time. The registry record does not report how the measured marker relates to later clinical outcomes in these participants. The endpoint should therefore be read as a biological measurement within the stated pre-surgical period, rather than as a direct measure of longer-term benefit or harm.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized by a mean and standard deviation. Understanding what these quantities represent helps distinguish an endpoint definition from a reported result. In this record, the endpoint is the percentage of Ki-67-positive cells in tumor specimens, and the stated timeframe runs from baseline to up to 4 weeks.

What does a mean describe?

As a general statistical explanation, a mean is an average across the observations included in an analysis. For a continuous outcome, it gives a concise description of the group's central level on the measurement scale. Here, that scale is the percentage of Ki-67-positive cells. A mean can make a group-level pattern easier to describe, but it does not show whether individual participants had similar values or widely varying ones. The registry specifies a mean as the outcome parameter but does not report the mean values or the estimated change.

What does a standard deviation describe?

As a general explanation, a standard deviation describes the spread of observations around their mean. It is not the same as the uncertainty in the mean: variability among participants and precision of a group estimate are related but different concepts. Precision also depends on aspects of the data and analysis that are not fully described in this record. The registry specifies standard deviation as the dispersion measure, but does not report its value for the endpoint.

How should baseline and follow-up measurements be considered?

When an outcome is measured at baseline and again during follow-up, one common analytic idea is to examine within-participant change. In general, a paired analysis uses the relationship between each participant's measurements; an analysis that treats measurements as independent would not use that pairing in the same way. The registry describes a change in tumor proliferation and gives a baseline-to-up-to-4-weeks timeframe, but does not identify the analysis method used. It is therefore not appropriate to state that a paired test, a particular model, or an adjustment was used.

A change score and a comparison of group means at different times are also not automatically identical analyses. Their estimates and uncertainty can depend on the chosen method and on how measurements are handled. The statistical analysis plan and the precise definition of the analyzed change are not reported in the registry record.

What would a confidence interval add?

As a general statistical explanation, a confidence interval describes the uncertainty around an estimate under a specified analysis. It helps readers consider which effect sizes are compatible with the observed data, rather than relying only on a single point estimate. A narrow interval indicates greater precision than a wide interval, given the same scale and interpretation. No confidence interval for the primary outcome is reported in the registry record. Its width, and thus the precision of the estimated change, cannot be evaluated.

What does a p-value answer?

As a general explanation, a p-value is calculated under a specified statistical model and null hypothesis. It does not measure the size of an effect, establish that a result is clinically important, or give the probability that a hypothesis is true. A p-value is most informative alongside an effect estimate and its uncertainty. The registry record does not report a p-value for the primary outcome or state the inferential test used. No conclusion about statistical significance can be drawn from the endpoint description alone.

Why does the single-group design matter?

For a study with a concurrent control group, a treatment comparison can be based on differences between groups, subject to the design and analysis assumptions. This study is single group, has allocation listed as not applicable, and has no masking. A baseline measurement can provide a reference for describing change, but it is not a parallel control group. As a general point, changes over time can reflect more than the intervention itself. Without a comparison group or other clearly reported method to address alternative explanations, observed change cannot be attributed to metformin alone.

The registry lists planning assumptions for sample-size illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. Those are planning assumptions for an illustration, not evidence that this trial used that design. They do not match the recorded single-group structure. The registry does not report the trial's own sample-size justification, and no numerical planning output is stated in the registry record.

For continuous outcomes, over-dispersion generally means that variability is greater than a model assumes; when that happens, model-based standard errors can be too small and intervals can be too narrow if the extra variability is ignored. This is a general explanation, not a claim that over-dispersion was present or modeled in this trial. The registry identifies a standard deviation but does not report a model or a check of its assumptions.

The record lists one outcome measure and one analysis. It does not state whether the analysis was prespecified in a detailed plan, whether any outcomes or analyses were changed, or how multiple testing was handled. One listed outcome and one listed analysis do not provide a full account of all analyses that may have been conducted. Such details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one analysis. It does not report a detailed statistical analysis plan, a hierarchy of outcomes, or a procedure for adjusting for multiple comparisons. The number of listed outcomes and analyses describes the registry entry; it does not establish that no other analyses were conducted. Whether multiplicity was considered, and how, is not reported in the registry record.

The primary outcome analysis population is described as 33 evaluable metformin-treated participants. Enrollment is listed as 35. The record does not define evaluability, explain why the analysis population differs from enrollment, or state whether participants without usable measurements were excluded. It does not describe missing-data methods, imputation, sensitivity analyses, or the number of missing endpoint values. These details are not reported in the registry record.

As a general statistical point, missingness can matter when the availability of measurements is related to participant characteristics or outcomes. An analysis of observed measurements may not fully represent the enrolled group if missingness is informative. That concern cannot be assessed from the registry description alone; no particular missing-data pattern should be assumed.

The record does not specify whether the primary analysis followed an intention-to-treat approach, a per-protocol approach, or another analysis-population definition. It does identify the evaluable metformin-treated group as the population included in the analysis. The criteria for inclusion and the handling of protocol deviations are not reported in the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry records 33 participants at risk for serious adverse events, zero with a serious adverse event, and zero deaths. It also records 33 participants at risk for other adverse events, with 29 affected. These are counts within the metformin group, not comparisons between treatment groups. The registry lists no serious adverse event terms.

The categories should be kept distinct: the zero count applies to serious adverse events and deaths, while the 29 count is recorded for other adverse events. The record does not provide descriptions of those other events, their severity, timing, duration, or whether participants experienced more than one event. It also does not explain how adverse events were collected or classified. Those details are not reported in the registry record.

As a general interpretation, an observed count is a description of what the registry records for the stated group and risk population. It does not show what would have occurred under a different treatment or in the absence of treatment. With no parallel control group, these figures cannot establish a comparative safety difference. Zero recorded serious adverse events also does not establish that the risk of such events is absent; it is a count from this study's recorded group, not proof about risk outside it.

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

This registry record describes a phase II, single-group pre-surgical study of metformin and identifies tumor proliferation measured by the percentage of Ki-67-positive cells as its primary endpoint. It gives a measurement timeframe from baseline to up to 4 weeks and states that 33 evaluable metformin-treated participants were included in the analysis. It also records the enrollment figure and adverse-event counts. These registry entries establish the study's setting and intended measurement, but not the direction or magnitude of the endpoint result.

The numerical outcome results are not reported in the registry record. There is no reported mean change, spread estimate, confidence interval, or p-value with which to assess the observed outcome or its precision. The endpoint description alone cannot show whether the marker increased, decreased, or remained similar. It also cannot establish whether any observed change would be statistically distinguishable from random variation.

Even if a before-and-after change were reported, the design would constrain what it means. A single-group study has no concurrent control group against which to compare the change. As a general principle, temporal change can have explanations other than the intervention, so a within-group pattern does not by itself establish a causal treatment effect. The registry record does not describe a method that resolves this limitation.

The endpoint is a biological measure in tumor specimens over a short, pre-surgical period. It is not a reported measure of longer-term clinical outcomes. The registry record does not report those outcomes or a relationship between the marker and subsequent outcomes in this study. The adverse-event counts likewise describe recorded events in the metformin group and do not establish comparative safety.

The appropriate reading is therefore limited: the record identifies the question, design, endpoint, analysis population, and recorded safety counts, while leaving the numerical primary result and its uncertainty unreported. It does not support a conclusion about the size of a biological effect, a causal treatment effect, or outcomes beyond the stated measurement.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between measuring change and establishing a treatment effect. A baseline-to-follow-up endpoint can describe a pattern within participants receiving an intervention. Without a concurrent comparison group, however, that pattern does not by itself show what would have happened under another condition. The single-group design makes that distinction central to interpreting any reported change.

The endpoint is also a useful example of how a measurement scale and summary statistic shape interpretation. The percentage of Ki-67-positive cells is a continuous measure, and the registry specifies a mean and standard deviation. Those quantities describe the center and spread of the analyzed values. They do not replace an effect estimate with an uncertainty interval, and the registry record does not report the numerical result needed to assess either.

Analysis populations matter as well. The registry reports enrollment of 35 and says that 33 evaluable metformin-treated participants were included in the outcome analysis, but does not explain the evaluability criteria or the difference between these counts. That gap illustrates why a clear account of inclusion, missing measurements, and analysis sets is important when evaluating how broadly a result applies.

Finally, the record shows why planning illustrations must be separated from a trial's actual design and findings. The listed sample-size assumptions describe a two-arm planning framework, while the study itself is recorded as single group. Planning calculations are not observed results, do not supply an absent endpoint estimate, and do not resolve the limits of a non-comparative design. In this case, design details are available, but numerical outcome reporting is not.

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 most direct limitation for interpreting the primary endpoint is that its numerical results are not reported in the registry record. The record gives the measure, summary type, timeframe, and analysis population, but not the actual mean values, estimated change, standard deviation, confidence interval, or inferential result. Consequently, neither effect magnitude nor precision can be assessed.

The single-group design does not include a concurrent control group. Baseline is a measurement occasion, not a separate untreated arm, so any observed change would not alone identify a causal effect of metformin. Masking is listed as none. The registry does not report further procedures that might address sources of bias or alternative explanations.

The outcome is assessed in the pre-surgical period, with a timeframe of baseline to up to 4 weeks. The registry does not report longer-term follow-up outcomes or the relationship between the tumor marker and later clinical outcomes. The result, even if numerically reported, would be limited to the endpoint and period described unless supported by additional evidence.

The analysis includes 33 evaluable metformin-treated participants, while enrollment is listed as 35. The registry does not define evaluability, explain the analysis-population count, or describe missing-data handling. This limits assessment of how the analyzed participants relate to those enrolled. The registry also does not report the specific statistical method, model assumptions, detailed endpoint analysis, or a full multiplicity plan.

Safety reporting is limited to counts and does not include serious adverse event terms or details for the other recorded adverse events. A comparator is absent, so comparative safety cannot be evaluated from these counts. The registry does not report the metformin regimen or specimen-collection schedule, details that would help characterize the intervention and measurement process.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pre-Surgical Study: Effect of Metformin on Breast Cancer Proliferation — NCT00930579.
• Registry record last updated 2022-10-20; status last verified 2022-10.
• Results first posted 2022-10-20.
• 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

NCT00930579 is a completed phase II, single-group pre-surgical study sponsored by Columbia University. It enrolled 35 participants with breast cancer and evaluated metformin in women with newly diagnosed early invasive breast cancer. The registry lists no masking and no randomized allocation.

The primary outcome is tumor proliferation in tumor specimens, measured as the percentage of Ki-67-positive cells from baseline to up to 4 weeks. It is specified as a mean with standard deviation. The registry says 33 evaluable metformin-treated participants were included in the analysis, but does not report numerical endpoint results or explain the analysis-population criteria.

The registry records zero serious adverse events and zero deaths among 33 at risk, and 29 participants with other adverse events among 33 at risk. It lists one outcome measure and one analysis. The numerical primary result, its precision, detailed missing-data methods, and the trial's own sample-size justification are not reported in the registry record.